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749 results on '"Dionisi-Vici, C."'

3. Newborn screening for homocystinurias: recent recommendations versus current practice

Author

Keller, R., Chrastina, P., Pavlíková, M., Gouveia, S., Ribes, A., Kölker, S., Blom, H. J., Baumgartner, M. R., Bártl, J., Dionisi Vici, C., Gleich, F., Morris, A. A., Kožich, V., Huemer, M., and individual contributors of the European Network and Registry for Homocystinurias and Methylation Defects (E-HOD), Barić, I., Ben-Omran, T., Blasco-Alonso, J., Bueno Delgado, M. A., Carducci, C., Cassanello, M., Cerone, R., Couce, M. L., Crushell, E., Delgado Pecellin, C., Dulin, E., Espada, M., Ferino, G., Fingerhut, R., Garcia Jimenez, I., Gonzalez Gallego, I., González-Irazabal, Y., Gramer, G., Juan Fita, M. J., Karg, E., Klein, J., Konstantopoulou, V., la Marca, G., Leão Teles, E., Leuzzi, V., Lilliu, F., Lopez, R. M., Lund, A. M., Mayne, P., Meavilla, S., Moat, S. J., Okun, J. G., Pasquini, E., Pedron-Giner, C., Racz, G. Z., Ruiz Gomez, M. A., Vilarinho, L., Yahyaoui, R., Zerjav Tansek, M., Zetterström, R. H., and Zeyda, M.

Published
2018
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4. Acid sphingomyelinase deficiency (ASMD): addressing knowledge gaps in unmet needs and patient journey in Italy-a Delphi consensus

Author

Scarpa, M, Barbato, A, Bisconti, A, Burlina, A, Concolino, D, Deodato, F, Di Rocco, M, Dionisi-Vici, C, Donati, M, Fecarotta, S, Fiumara, A, Galeone, C, Giona, F, Giuffrida, G, Manna, R, Mariani, P, Pession, A, Scopinaro, A, Spada, M, Spandonaro, F, Trifirò, G, Carubbi, F, Cappellini, M, Scarpa, Maurizio, Barbato, Antonio, Bisconti, Annalisa, Burlina, Alberto, Concolino, Daniela, Deodato, Federica, Di Rocco, Maja, Dionisi-Vici, Carlo, Donati, Maria Alice, Fecarotta, Simona, Fiumara, Agata, Galeone, Carlotta, Giona, Fiorina, Giuffrida, Gaetano, Manna, Raffaele, Mariani, Paolo, Pession, Andrea, Scopinaro, Annalisa, Spada, Marco, Spandonaro, Federico, Trifirò, Gianluca, Carubbi, Francesca, Cappellini, Maria Domenica, Scarpa, M, Barbato, A, Bisconti, A, Burlina, A, Concolino, D, Deodato, F, Di Rocco, M, Dionisi-Vici, C, Donati, M, Fecarotta, S, Fiumara, A, Galeone, C, Giona, F, Giuffrida, G, Manna, R, Mariani, P, Pession, A, Scopinaro, A, Spada, M, Spandonaro, F, Trifirò, G, Carubbi, F, Cappellini, M, Scarpa, Maurizio, Barbato, Antonio, Bisconti, Annalisa, Burlina, Alberto, Concolino, Daniela, Deodato, Federica, Di Rocco, Maja, Dionisi-Vici, Carlo, Donati, Maria Alice, Fecarotta, Simona, Fiumara, Agata, Galeone, Carlotta, Giona, Fiorina, Giuffrida, Gaetano, Manna, Raffaele, Mariani, Paolo, Pession, Andrea, Scopinaro, Annalisa, Spada, Marco, Spandonaro, Federico, Trifirò, Gianluca, Carubbi, Francesca, and Cappellini, Maria Domenica

Abstract

Acid sphingomyelinase deficiency (ASMD) is an ultra-rare disease, and several gaps of knowledge on various issues remain, particularly at a regional/national level. Expert opinions collected through well-defined consensus methodologies are increasingly used to make available reliable information in the context of rare/ultra-rare diseases. With the aim to provide indications on infantile neurovisceral ASMD (also formerly known as Niemann–Pick disease type A), chronic neurovisceral ASMD (formerly known as Niemann–Pick disease type A/B) and chronic visceral ASMD (formerly known as Niemann–Pick disease type B) in Italy, we conducted a Delphi consensus of experts focused on five main areas: (i) patients and disease characteristics; (ii) unmet needs and quality of life; (iii) diagnostic issues; (iv) treatment-related aspects; and (v) patient journey. Pre-specified, objective criteria were used to outline the multidisciplinary panel, based on 19 Italian experts in ASMD in paediatric and adult patients from different Italian Regions, including both clinicians (n = 16) and ASMD patients’ advocacy or payors with expertise in rare diseases (n = 3). During two Delphi rounds, a high ratio of agreement was found on several topics related to ASMD characteristics, diagnosis, management and disease burden. Our findings may provide valuable indications for management of ASMD at a public health level in Italy.

Published
2023

5. Diagnostic Approach to Acute Liver Failure in Children: A Position Paper by the SIGENP Liver Disease Working Group

Author

Di Giorgio, A, Bartolini, E, Calvo, P, Cananzi, M, Cirillo, F, Della Corte, C, Dionisi-Vici, C, Indolfi, G, Iorio, R, Maggiore, G, Mandato, C, Nebbia, G, Nicastro, E, Pinon, M, Ranucci, G, Sciveres, M, Vajro, P, D'Antiga, L, Di Giorgio A., Bartolini E., Calvo P. L., Cananzi M., Cirillo F., Della Corte C., Dionisi-Vici C., Indolfi G., Iorio R., Maggiore G., Mandato C., Nebbia G., Nicastro E., Pinon M., Ranucci G., Sciveres M., Vajro P., D'Antiga L., Di Giorgio, A, Bartolini, E, Calvo, P, Cananzi, M, Cirillo, F, Della Corte, C, Dionisi-Vici, C, Indolfi, G, Iorio, R, Maggiore, G, Mandato, C, Nebbia, G, Nicastro, E, Pinon, M, Ranucci, G, Sciveres, M, Vajro, P, D'Antiga, L, Di Giorgio A., Bartolini E., Calvo P. L., Cananzi M., Cirillo F., Della Corte C., Dionisi-Vici C., Indolfi G., Iorio R., Maggiore G., Mandato C., Nebbia G., Nicastro E., Pinon M., Ranucci G., Sciveres M., Vajro P., and D'Antiga L.

Abstract

Acute liver failure (ALF) is a clinical condition characterized by the abrupt onset of coagulopathy and biochemical evidence of hepatocellular injury, leading to rapid deterioration of liver cell function. In children, ALF has been characterized by raised transaminases, coagulopathy, and no known evidence of pre-existing chronic liver disease; unlike in adults, the presence of hepatic encephalopathy is not required to establish the diagnosis. Although rare, ALF has a high mortality rate without liver transplantation (LT). Etiology of ALF varies with age and geographical location, although it may remain indeterminate in a significant proportion of cases. However, identifying its etiology is crucial to undertake disease-specific management and evaluate indication to LT. In this position statement, the Liver Disease Working Group of the Italian Society of Gastroenterology, Hepatology and Nutrition (SIGENP) reviewed the most relevant studies on pediatric ALF to provide recommendations on etiology, clinical features and diagnostic work-up of neonates, infants and children presenting with ALF. Recommendations on medical management and transplant candidacy will be discussed in a following consensus conference.

Published
2021

7. Children with special health care needs attending emergency department in Italy: analysis of 3479 cases

Author

Cianci, P, D'Apolito, V, Moretti, A, Barbagallo, M, Paci, S, Carbone, M, Lubrano, R, Urbino, A, Dionisi Vici, C, Memo, L, Zampino, G, La Marca, G, Villani, A, Corsello, G, Selicorni, A, Campania, A, Geremia, C, Castagno, E, Masi, S, Poggi, G, Vestri, M, Fossali, E, Rocchi, A, Dadalt, L, Arrighini, A, Chiappa, S, Renna, S, Piccotti, E, Borgna, C, Govoni, M, Biondi, A, Fossati, C, Iughetti, L, Bertolani, P, Salvatoni, A, Agosti, M, Fuca, F, Ilardi, A, Giuffrida, S, Diguardo, V, Boni, S, D'Antiga, L, Ruggeri, M, Chiaretti, A, Amarri, S, Peduto, A, Bernardi, F, Corsini, I, Deangelis, G, Ruberto, C, Zuccotti, G, Stringhi, C, Lombardi, G, Salladini, C, Dimichele, S, Parola, L, Porta, A, Biasucci, G, Bellini, M, Ortisi, M, Apuril, E, Midulla, F, Tarani, L, Parlapiano, G, Lietti, D, Sforzini, C, Marseglia, G, Savasta, S, Falsaperla, R, Vitaliti, M, Chiarelli, F, Rossi, N, Banderali, G, Giacchero, R, Bernardo, L, Pinto, F, Fabiani, E, Ficcadenti, A, Pellegrini, G, Giacoma, S, Biban, P, Spada, S, Tipo, V, Ghitti, C, Bolognini, S, Mariani, G, Russo, A, Colella, M, Verrico, A, Bruni, P, Poddighe, D, Cagnoli, G, Morandi, F, Gadaleta, A, Barbi, E, Bruno, I, Graziano, R, Sgaramella, P, Catalani, M, Baldoni, I, Colarusso, G, Galvagno, G, Barone, A, Longo, A, Nardella, G, Portale, G, Garigali, G, Bona, G, Erbela, M, Agostiniani, R, Nanni, L, Schieven, E, Dona, M, Varisco, T, Russo, F, Distefano, V, Dipietro, F, Tarallo, L, Imperato, L, Parisi, G, Salzano, R, Raiola, G, Talarico, V, Bellu, R, Cannone, A, Ferrante, P, Cianci P., D'Apolito V., Moretti A., Barbagallo M., Paci S., Carbone M. T., Lubrano R., Urbino A., Dionisi Vici C., Memo L., Zampino G., La Marca G., Villani A., Corsello G., Selicorni A., Campania A., Geremia C., Castagno E., Masi S., Poggi G., Vestri M., Fossali E., Rocchi A., DaDalt L., Arrighini A., Chiappa S., Renna S., Piccotti E., Borgna C., Govoni M. R., Biondi A., Fossati C., Iughetti L., Bertolani P., Salvatoni A., Agosti M., Fuca F., Ilardi A., Giuffrida S., DiGuardo V., Boni S., D'Antiga L., Ruggeri M., Chiaretti A., Amarri S., Peduto A., Bernardi F., Corsini I., DeAngelis G. L., Ruberto C., Zuccotti G. V., Stringhi C., Lombardi G., Salladini C., DiMichele S., Parola L., Porta A., Biasucci G., Bellini M., Ortisi M. T., Apuril E., Midulla F., Tarani L., Parlapiano G., Lietti D., Sforzini C., Marseglia G. L., Savasta S., Falsaperla R., Vitaliti M. C., Chiarelli F., Rossi N., Banderali G., Giacchero R., Bernardo L., Pinto F., Fabiani E., Ficcadenti A., Pellegrini G., Giacoma S., Biban P., Spada S., Tipo V., Ghitti C., Bolognini S., Mariani G., Russo A., Colella M. G., Verrico A., Bruni P., Poddighe D., Cagnoli G., Morandi F., Gadaleta A., Barbi E., Bruno I. I., Graziano R., Sgaramella P., Catalani M. P., Baldoni I., Colarusso G., Galvagno G., Barone A. P., Longo A., Nardella G., Portale G., Garigali G., Bona G., Erbela M., Agostiniani R., Nanni L., Schieven E., Dona M., Varisco T., Russo F., DiStefano V. A., DiPietro F., Tarallo L., Imperato L., Parisi G., Salzano R., Raiola G., Talarico V., Bellu R., Cannone A., Ferrante P., Cianci, P, D'Apolito, V, Moretti, A, Barbagallo, M, Paci, S, Carbone, M, Lubrano, R, Urbino, A, Dionisi Vici, C, Memo, L, Zampino, G, La Marca, G, Villani, A, Corsello, G, Selicorni, A, Campania, A, Geremia, C, Castagno, E, Masi, S, Poggi, G, Vestri, M, Fossali, E, Rocchi, A, Dadalt, L, Arrighini, A, Chiappa, S, Renna, S, Piccotti, E, Borgna, C, Govoni, M, Biondi, A, Fossati, C, Iughetti, L, Bertolani, P, Salvatoni, A, Agosti, M, Fuca, F, Ilardi, A, Giuffrida, S, Diguardo, V, Boni, S, D'Antiga, L, Ruggeri, M, Chiaretti, A, Amarri, S, Peduto, A, Bernardi, F, Corsini, I, Deangelis, G, Ruberto, C, Zuccotti, G, Stringhi, C, Lombardi, G, Salladini, C, Dimichele, S, Parola, L, Porta, A, Biasucci, G, Bellini, M, Ortisi, M, Apuril, E, Midulla, F, Tarani, L, Parlapiano, G, Lietti, D, Sforzini, C, Marseglia, G, Savasta, S, Falsaperla, R, Vitaliti, M, Chiarelli, F, Rossi, N, Banderali, G, Giacchero, R, Bernardo, L, Pinto, F, Fabiani, E, Ficcadenti, A, Pellegrini, G, Giacoma, S, Biban, P, Spada, S, Tipo, V, Ghitti, C, Bolognini, S, Mariani, G, Russo, A, Colella, M, Verrico, A, Bruni, P, Poddighe, D, Cagnoli, G, Morandi, F, Gadaleta, A, Barbi, E, Bruno, I, Graziano, R, Sgaramella, P, Catalani, M, Baldoni, I, Colarusso, G, Galvagno, G, Barone, A, Longo, A, Nardella, G, Portale, G, Garigali, G, Bona, G, Erbela, M, Agostiniani, R, Nanni, L, Schieven, E, Dona, M, Varisco, T, Russo, F, Distefano, V, Dipietro, F, Tarallo, L, Imperato, L, Parisi, G, Salzano, R, Raiola, G, Talarico, V, Bellu, R, Cannone, A, Ferrante, P, Cianci P., D'Apolito V., Moretti A., Barbagallo M., Paci S., Carbone M. T., Lubrano R., Urbino A., Dionisi Vici C., Memo L., Zampino G., La Marca G., Villani A., Corsello G., Selicorni A., Campania A., Geremia C., Castagno E., Masi S., Poggi G., Vestri M., Fossali E., Rocchi A., DaDalt L., Arrighini A., Chiappa S., Renna S., Piccotti E., Borgna C., Govoni M. R., Biondi A., Fossati C., Iughetti L., Bertolani P., Salvatoni A., Agosti M., Fuca F., Ilardi A., Giuffrida S., DiGuardo V., Boni S., D'Antiga L., Ruggeri M., Chiaretti A., Amarri S., Peduto A., Bernardi F., Corsini I., DeAngelis G. L., Ruberto C., Zuccotti G. V., Stringhi C., Lombardi G., Salladini C., DiMichele S., Parola L., Porta A., Biasucci G., Bellini M., Ortisi M. T., Apuril E., Midulla F., Tarani L., Parlapiano G., Lietti D., Sforzini C., Marseglia G. L., Savasta S., Falsaperla R., Vitaliti M. C., Chiarelli F., Rossi N., Banderali G., Giacchero R., Bernardo L., Pinto F., Fabiani E., Ficcadenti A., Pellegrini G., Giacoma S., Biban P., Spada S., Tipo V., Ghitti C., Bolognini S., Mariani G., Russo A., Colella M. G., Verrico A., Bruni P., Poddighe D., Cagnoli G., Morandi F., Gadaleta A., Barbi E., Bruno I. I., Graziano R., Sgaramella P., Catalani M. P., Baldoni I., Colarusso G., Galvagno G., Barone A. P., Longo A., Nardella G., Portale G., Garigali G., Bona G., Erbela M., Agostiniani R., Nanni L., Schieven E., Dona M., Varisco T., Russo F., DiStefano V. A., DiPietro F., Tarallo L., Imperato L., Parisi G., Salzano R., Raiola G., Talarico V., Bellu R., Cannone A., and Ferrante P.

Abstract

Background: Although children with special health care needs (CSHCN) represent a minority of the population, they go through more hospitalizations, more admissions to the Emergency Department (ED), and receive a major number of medical prescriptions, in comparison to general pediatric population. Objectives of the study were to determine the reasons for admission to the ED in Italian CSHCN, and to describe the association between patient’s demographic data, clinical history, and health services requirements. Methods: Ad hoc web site was created to collect retrospective data of 3479 visits of CSHCN to the ED in 58 Italian Hospitals. Results: Seventy-two percent of patients admitted to ED were affected by a previously defined medical condition. Most of the ED admissions were children with syndromic conditions (54%). 44.2% of the ED admissions were registered during the night-time and/or at the weekends. The hospitalization rate was of 45.6% among patients admitted to the ED. The most common reason for admission to the ED was the presence of respiratory symptoms (26.6%), followed by gastrointestinal problems (21.3%) and neurological disorders (18.2%). 51.4% of the access were classified as ‘urgent’, with a red/yellow triage code. Considering the type of ED, 61.9% of the visits were conducted at the Pediatric EDs (PedEDs), 33.5% at the Functional EDs (FunEDs) and 4.6% at the Dedicated EDs (DedEDs). Patients with more complex clinical presentation were more likely to be evaluated at the PedEDs. CSHCN underwent to a higher number of medical procedures at the PedEDs, more in comparison to other EDs. Children with medical devices were directed to a PedED quite exclusively when in need for medical attention. Subjects under multiple anti-epileptic drug therapy attended to PedEDs or FunEDs generally. Patients affected by metabolic diseases were more likely to look for medical attention at FunEDs. Syndromic patients mostly required medical attention at the DedEDs. Conclusions

Published
2020

8. Children with special health care needs attending emergency department in Italy: analysis of 3479 cases

Author

Cianci, P., D'Apolito, V., Moretti, A., Barbagallo, M., Paci, S., Carbone, M. T., Lubrano, R., Urbino, A., Dionisi Vici, C., Memo, L., Zampino, G., La Marca, G., Villani, A., Corsello, G., Selicorni, A., Campania, A., Geremia, C., Castagno, E., Masi, S., Poggi, G., Vestri, M., Fossali, E., Rocchi, A., Dadalt, L., Arrighini, A., Chiappa, S., Renna, S., Piccotti, E., Borgna, C., Govoni, M. R., Biondi, A., Fossati, C., Iughetti, L., Bertolani, P., Salvatoni, A., Agosti, M., Fuca, F., Ilardi, A., Giuffrida, S., Diguardo, V., Boni, S., D'Antiga, L., Ruggeri, M., Chiaretti, A., Amarri, S., Peduto, A., Bernardi, F., Corsini, I., Deangelis, G. L., Ruberto, C., Zuccotti, G. V., Stringhi, C., Lombardi, G., Salladini, C., Dimichele, S., Parola, L., Porta, A., Biasucci, G., Bellini, M., Ortisi, M. T., Apuril, E., Midulla, F., Tarani, L., Parlapiano, G., Lietti, D., Sforzini, C., Marseglia, G. L., Savasta, S., Falsaperla, R., Vitaliti, M. C., Chiarelli, F., Rossi, N., Banderali, G., Giacchero, R., Bernardo, L., Pinto, F., Fabiani, E., Ficcadenti, A., Pellegrini, G., Giacoma, S., Biban, P., Spada, S., Tipo, V., Ghitti, C., Bolognini, S., Mariani, G., Russo, A., Colella, M. G., Verrico, A., Bruni, P., Poddighe, D., Cagnoli, G., Morandi, F., Gadaleta, A., Barbi, E., Bruno, I. I., Graziano, R., Sgaramella, P., Catalani, M. P., Baldoni, I., Colarusso, G., Galvagno, G., Barone, A. P., Longo, A., Nardella, G., Portale, G., Garigali, G., Bona, G., Erbela, M., Agostiniani, R., Nanni, L., Schieven, E., Dona, M., Varisco, T., Russo, F., Distefano, V. A., Dipietro, F., Tarallo, L., Imperato, L., Parisi, G., Salzano, R., Raiola, G., Talarico, V., Bellu, R., Cannone, A., Ferrante, P., Cianci, P, D'Apolito, V, Moretti, A, Barbagallo, M, Paci, S, Carbone, M, Lubrano, R, Urbino, A, Dionisi Vici, C, Memo, L, Zampino, G, La Marca, G, Villani, A, Corsello, G, Selicorni, A, Campania, A, Geremia, C, Castagno, E, Masi, S, Poggi, G, Vestri, M, Fossali, E, Rocchi, A, Dadalt, L, Arrighini, A, Chiappa, S, Renna, S, Piccotti, E, Borgna, C, Govoni, M, Biondi, A, Fossati, C, Iughetti, L, Bertolani, P, Salvatoni, A, Agosti, M, Fuca, F, Ilardi, A, Giuffrida, S, Diguardo, V, Boni, S, D'Antiga, L, Ruggeri, M, Chiaretti, A, Amarri, S, Peduto, A, Bernardi, F, Corsini, I, Deangelis, G, Ruberto, C, Zuccotti, G, Stringhi, C, Lombardi, G, Salladini, C, Dimichele, S, Parola, L, Porta, A, Biasucci, G, Bellini, M, Ortisi, M, Apuril, E, Midulla, F, Tarani, L, Parlapiano, G, Lietti, D, Sforzini, C, Marseglia, G, Savasta, S, Falsaperla, R, Vitaliti, M, Chiarelli, F, Rossi, N, Banderali, G, Giacchero, R, Bernardo, L, Pinto, F, Fabiani, E, Ficcadenti, A, Pellegrini, G, Giacoma, S, Biban, P, Spada, S, Tipo, V, Ghitti, C, Bolognini, S, Mariani, G, Russo, A, Colella, M, Verrico, A, Bruni, P, Poddighe, D, Cagnoli, G, Morandi, F, Gadaleta, A, Barbi, E, Bruno, I, Graziano, R, Sgaramella, P, Catalani, M, Baldoni, I, Colarusso, G, Galvagno, G, Barone, A, Longo, A, Nardella, G, Portale, G, Garigali, G, Bona, G, Erbela, M, Agostiniani, R, Nanni, L, Schieven, E, Dona, M, Varisco, T, Russo, F, Distefano, V, Dipietro, F, Tarallo, L, Imperato, L, Parisi, G, Salzano, R, Raiola, G, Talarico, V, Bellu, R, Cannone, A, Ferrante, P, Paola Cianci, Valeria D'Apolito, Alex Moretti, Massimo Barbagallo, Sabrina Paci, Maria Teresa Carbone, Riccardo Lubrano, Antonio Urbino, Carlo Dionisi Vici, Luigi Memo, Giuseppe Zampino, Giancarlo La Marca, Alberto Villani, Giovanni Corsello, Angelo Selicorni, Cianci, P., D'Apolito, V., Moretti, A., Barbagallo, M., Paci, S., Carbone, M. T., Lubrano, R., Urbino, A., Dionisi Vici, C., Memo, L., Zampino, G., La Marca, G., Villani, A., Corsello, G., Selicorni, A., Campania, A., Geremia, C., Castagno, E., Masi, S., Poggi, G., Vestri, M., Fossali, E., Rocchi, A., Dadalt, L., Arrighini, A., Chiappa, S., Renna, S., Piccotti, E., Borgna, C., Govoni, M. R., Biondi, A., Fossati, C., Iughetti, L., Bertolani, P., Salvatoni, A., Agosti, M., Fuca, F., Ilardi, A., Giuffrida, S., Diguardo, V., Boni, S., D'Antiga, L., Ruggeri, M., Chiaretti, A., Amarri, S., Peduto, A., Bernardi, F., Corsini, I., Deangelis, G. L., Ruberto, C., Zuccotti, G. V., Stringhi, C., Lombardi, G., Salladini, C., Dimichele, S., Parola, L., Porta, A., Biasucci, G., Bellini, M., Ortisi, M. T., Apuril, E., Midulla, F., Tarani, L., Parlapiano, G., Lietti, D., Sforzini, C., Marseglia, G. L., Savasta, S., Falsaperla, R., Vitaliti, M. C., Chiarelli, F., Rossi, N., Banderali, G., Giacchero, R., Bernardo, L., Pinto, F., Fabiani, E., Ficcadenti, A., Pellegrini, G., Giacoma, S., Biban, P., Spada, S., Tipo, V., Ghitti, C., Bolognini, S., Mariani, G., Russo, A., Colella, M. G., Verrico, A., Bruni, P., Poddighe, D., Cagnoli, G., Morandi, F., Gadaleta, A., Barbi, E., Bruno, I. I., Graziano, R., Sgaramella, P., Catalani, M. P., Baldoni, I., Colarusso, G., Galvagno, G., Barone, A. P., Longo, A., Nardella, G., Portale, G., Garigali, G., Bona, G., Erbela, M., Agostiniani, R., Nanni, L., Schieven, E., Dona, M., Varisco, T., Russo, F., Distefano, V. A., Dipietro, F., Tarallo, L., Imperato, L., Parisi, G., Salzano, R., Raiola, G., Talarico, V., Bellu, R., Cannone, A., and Ferrante, P.

Subjects
Male, Metabolic disease, Hospitalization rate, Congenital skeletal condition, Children with special health care needs, Emergency department, Isolated CNS malformation, Metabolic diseases, Multiple AED therapy, Neuromuscular diseases, Syndromic disorders, True isolated microcephaly, 0302 clinical medicine, Clinical history, Medicine, Child, education.field_of_study, Neuromuscular disease, Settore MED/38, Disabled Children, Hospitalization, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Italy, Child, Preschool, Female, Children with special health care need, Emergency Service, Hospital, medicine.medical_specialty, Adolescent, Population, Triage Code, 03 medical and health sciences, Pharmacotherapy, 030225 pediatrics, Humans, Medical prescription, education, Retrospective Studies, Health Services Needs and Demand, Syndromic disorder, business.industry, Research, Infant, Newborn, Infant, 030208 emergency & critical care medicine, Children with special health care needs, Congenital skeletal conditions,Emergency department, Hospitalization rate, Isolated CNS malformation, Metabolic diseases, Multiple AED therapy, Neuromuscular diseases, Syndromic disorders, True isolated microcephaly, Family medicine, Chronic Disease, business, Facilities and Services Utilization
Abstract

Background Although children with special health care needs (CSHCN) represent a minority of the population, they go through more hospitalizations, more admissions to the Emergency Department (ED), and receive a major number of medical prescriptions, in comparison to general pediatric population. Objectives of the study were to determine the reasons for admission to the ED in Italian CSHCN, and to describe the association between patient’s demographic data, clinical history, and health services requirements. Methods Ad hoc web site was created to collect retrospective data of 3479 visits of CSHCN to the ED in 58 Italian Hospitals. Results Seventy-two percent of patients admitted to ED were affected by a previously defined medical condition. Most of the ED admissions were children with syndromic conditions (54%). 44.2% of the ED admissions were registered during the night-time and/or at the weekends. The hospitalization rate was of 45.6% among patients admitted to the ED. The most common reason for admission to the ED was the presence of respiratory symptoms (26.6%), followed by gastrointestinal problems (21.3%) and neurological disorders (18.2%). 51.4% of the access were classified as ‘urgent’, with a red/yellow triage code. Considering the type of ED, 61.9% of the visits were conducted at the Pediatric EDs (PedEDs), 33.5% at the Functional EDs (FunEDs) and 4.6% at the Dedicated EDs (DedEDs). Patients with more complex clinical presentation were more likely to be evaluated at the PedEDs. CSHCN underwent to a higher number of medical procedures at the PedEDs, more in comparison to other EDs. Children with medical devices were directed to a PedED quite exclusively when in need for medical attention. Subjects under multiple anti-epileptic drug therapy attended to PedEDs or FunEDs generally. Patients affected by metabolic diseases were more likely to look for medical attention at FunEDs. Syndromic patients mostly required medical attention at the DedEDs. Conclusions Access of CSHCN to an ED is not infrequent. For this reason, it is fundamental for pediatricians working in any kind of ED to increase their general knowledge about CHSCN and to gain expertise in the management of such patients and their related medical complexity.

Published
2020

9. Bi-allelic LETM1 variants perturb mitochondrial ion homeostasis leading to a clinical spectrum with predominant nervous system involvement

Author

Kaiyrzhanov, R., Mohammed, S.E.M., Maroofian, R., Husain, R.A., Catania, A., Torraco, A., Alahmad, A., Dutra-Clarke, M., Grønborg, S., Sudarsanam, A., Vogt, J., Arrigoni, F., Baptista, J., Haider, S., Feichtinger, R.G., Bernardi, P., Zulian, A., Gusic, M., Efthymiou, S., Bai, R., Bibi, F., Horga, A., Martinez-Agosto, J.A., Lam, A., Manole, A, Rodriguez, D.P., Durigon, R., Pyle, A., Albash, B., Dionisi-Vici, C., Murphy, D., Martinelli, D., Bugiardini, E., Allis, K., Lamperti, C., Reipert, S., Risom, L., Laugwitz, L., Nottia, M. Di, McFarland, R., Vilarinho, L., Hanna, M., Prokisch, H., Mayr, J.A., Bertini, E.S., Ghezzi, D., Østergaard, E., Wortmann, S.B., Carrozzo, R., Haack, T.B., Taylor, R.W., Spinazzola, A., Nowikovsky, K., Houlden, H., Kaiyrzhanov, R., Mohammed, S.E.M., Maroofian, R., Husain, R.A., Catania, A., Torraco, A., Alahmad, A., Dutra-Clarke, M., Grønborg, S., Sudarsanam, A., Vogt, J., Arrigoni, F., Baptista, J., Haider, S., Feichtinger, R.G., Bernardi, P., Zulian, A., Gusic, M., Efthymiou, S., Bai, R., Bibi, F., Horga, A., Martinez-Agosto, J.A., Lam, A., Manole, A, Rodriguez, D.P., Durigon, R., Pyle, A., Albash, B., Dionisi-Vici, C., Murphy, D., Martinelli, D., Bugiardini, E., Allis, K., Lamperti, C., Reipert, S., Risom, L., Laugwitz, L., Nottia, M. Di, McFarland, R., Vilarinho, L., Hanna, M., Prokisch, H., Mayr, J.A., Bertini, E.S., Ghezzi, D., Østergaard, E., Wortmann, S.B., Carrozzo, R., Haack, T.B., Taylor, R.W., Spinazzola, A., Nowikovsky, K., and Houlden, H.

Abstract

Contains fulltext : 283148.pdf (Publisher’s version ) (Open Access), Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) encodes an inner mitochondrial membrane protein with an osmoregulatory function controlling mitochondrial volume and ion homeostasis. The putative association of LETM1 with a human disease was initially suggested in Wolf-Hirschhorn syndrome, a disorder that results from de novo monoallelic deletion of chromosome 4p16.3, a region encompassing LETM1. Utilizing exome sequencing and international gene-matching efforts, we have identified 18 affected individuals from 11 unrelated families harboring ultra-rare bi-allelic missense and loss-of-function LETM1 variants and clinical presentations highly suggestive of mitochondrial disease. These manifested as a spectrum of predominantly infantile-onset (14/18, 78%) and variably progressive neurological, metabolic, and dysmorphic symptoms, plus multiple organ dysfunction associated with neurodegeneration. The common features included respiratory chain complex deficiencies (100%), global developmental delay (94%), optic atrophy (83%), sensorineural hearing loss (78%), and cerebellar ataxia (78%) followed by epilepsy (67%), spasticity (53%), and myopathy (50%). Other features included bilateral cataracts (42%), cardiomyopathy (36%), and diabetes (27%). To better understand the pathogenic mechanism of the identified LETM1 variants, we performed biochemical and morphological studies on mitochondrial K(+)/H(+) exchange activity, proteins, and shape in proband-derived fibroblasts and muscles and in Saccharomyces cerevisiae, which is an important model organism for mitochondrial osmotic regulation. Our results demonstrate that bi-allelic LETM1 variants are associated with defective mitochondrial K(+) efflux, swollen mitochondrial matrix structures, and loss of important mitochondrial oxidative phosphorylation protein components, thus highlighting the implication of perturbed mitochondrial osmoregulation caused by LETM1 variants in neurological and mitochondrial patholog

Published
2022

10. Genetic disorders of cellular trafficking

Author

Garcia-Cazorla A, De Oyarzabal-Sanz AL, Saudubray JM, Martinelly D, and Dionisi-Vici C

Subjects
autophagy, membrane contact sites, cellular trafficking, vesicular trafficking, inherited metabolic diseases
Abstract

Cellular trafficking is essential to maintain critical biological functions. Mutations in 346 genes, most of them described in the last 5 years, are associated with disorders of cellular trafficking. Whereas initially restricted to membrane trafficking, the recent detection of many diseases has contributed to the discovery of new biological pathways. Accordingly, we propose to redesign this rapidly growing group of diseases combining biological mechanisms and clinical presentation into the following categories: (i) membrane trafficking (including organelle-related); (ii) membrane contact sites; (iii) autophagy; (iv) cytoskeleton-related. We present the most recently described pathophysiological findings, disorders and phenotypes. Although all tissues and organs are affected, the nervous system is especially vulnerable.

Published
2022

11. Post-authorization safety study of Betaine anhydrous

Author

Mütze U, Gleich F, Garbade SF, Plisson C, Aldámiz-Echevarría L, Arrieta F, Ballhausen D, Zielonka M, Ramadža DP, Baumgartner MR, Cano A, Jiménez MCG, Dionisi-Vici C, Ješina P, Blom HJ, Couce ML, Olivas SM, Mention K, Mochel F, Morris AAM, Mundy H, Redonnet-Vernhet I, Santra S, Schiff M, Servais A, Vitoria I, Huemer M, Kožich V, and Kölker S

Subjects
homocystinuria, post-authorization safety study, Betaine anhydrous, rare disease, orphan drug, public private partnership, E-HOD
Abstract

Patient registries for rare diseases enable systematic data collection and can also be used to facilitate post-authorization safety studies (PASS) for orphan drugs. This study evaluates the PASS for betaine anhydrous (Cystadane®), conducted as public private partnership (PPP) between the European network and registry for homocystinurias and methylation defects (E-HOD) and the marketing authorization holder (MAH). Prospective data collection, 2013-2016, in a non-interventional, international, multicenter, registry study. Putative adverse and severe adverse events were reported to the MAH's pharmacovigilance. 130 individuals with vitamin B(6) non-responsive (N = 54) and partially responsive (N = 7) cystathionine beta-synthase (CBS) deficiency, as well as 5,10-methylenetetrahydrofolate reductase (MTHFR; N = 21) deficiency and cobalamin C (N = 48) disease were included. Median (range) duration of treatment with betaine anhydrous was 6.8 (0-9.8) years. The prescribed betaine dose exceeded the recommended maximum (6 g/day) in 49% of individuals older than 10 years because of continued dose adaptation to weight; however, with disease-specific differences (minimum: 31% in B(6) non-responsive CBS deficiency, maximum: 67% in MTHFR deficiency). Despite dose escalation no new or potential risk was identified. Combined disease-specific treatment decreased mean ± SD total plasma homocysteine concentrations from 203 ± 116 µmoL/L to 81 ± 51 µmoL/L (P < 0.0001), except in MTHFR deficiency. Recommendations for betaine anhydrous dosage were revised for individuals older than 10 years. PPPs between MAH and international scientific consortia can be considered a reliable model for implementing a PASS, reutilizing well-established structures and avoiding data duplication and fragmentation.

Published
2022

12. Evaluation of dietary treatment and amino acid supplementation in organic acidurias and urea‐cycle disorders: On the basis of information from a European multicenter registry

Author

Molema, Femke, Gleich, Florian, Burgard, Peter, van der Ploeg, Ans T., Summar, Marshall L., Chapman, Kimberly A., Barić, Ivo, Lund, Allan M., Kölker, Stefan, Williams, Monique, Hörster, F., Jelsig, A.M., de Lonlay, P., Wijburg, F.A., Bosch, A., Freisinger, P., Posset, R., Augoustides‐Savvopoulou, P., Avram, P., Deleanu, C., Baumgartner, M.R., Häberle, J., Blasco‐ Alonso, J., Burlina, A.B., Rubert, L., Cazorla, A. Garcia, Saladelafont, E. Cortes i, Dionisi‐ Vici, C., Martinelli, D., Dobbelaere, D., Mention, K., Grünewald, S., Chakrapani, A., Hwu, Wuh‐Liang, Chien, Yin‐Hsiu, Lee, Ni‐Chung, Karall, D., Scholl‐Bürgi, S., Lachmann, R., De Laet, C., Matsumoto, S., de Meirleir, L., Mühlhausen, C., Schiff, M., Peña‐Quintana, L., Djordjevic, M., Sarajlija, A., Sykut‐Cegielska, J., Wisniewska, A., Leao‐Teles, E., Alves, S., Vara, R., Vives‐Pinera, I., Ortega, D.G., Morris, A., Zeman, J., Honzik, T., Chabrol, B., Arnaudo, F., Cano, A., Thompson, N., Eyskens, F., Lindner, M., Lüsebrink, N., Jalan, A., Sokal, E., Legros, V., Nassogne, M.C., Additional individual contributors from E‐IMD, Pediatrics, Paediatric Metabolic Diseases, AGEM - Inborn errors of metabolism, ARD - Amsterdam Reproduction and Development, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), and E-IMD

Subjects
Adult, Male, Ornithine, medicine.medical_specialty, Propionic Acidemia, Adolescent, organic acidurias, Protein metabolism, Ornithine transcarbamylase, amino acid mixtures, Gastroenterology, Reference Daily Intake, Young Adult, chemistry.chemical_compound, Valine, Internal medicine, Genetics, medicine, Humans, Hyperammonemia, dietary and supplemental treatment, Registries, Amino Acids, branched-chain amino acids, Child, Amino Acid Metabolism, Inborn Errors, Urea Cycle Disorders, Inborn, Genetics (clinical), Retrospective Studies, L-citrulline and L-arginine, business.industry, urea-cycle disorders, Infant, Europe, Cross-Sectional Studies, Treatment Outcome, chemistry, Methylmalonic aciduria, Child, Preschool, Urea cycle, Dietary Supplements, Feasibility Studies, Female, Human medicine, Leucine, business
Abstract

Organic acidurias (OAD) and urea-cycle disorders (UCD) are rare inherited disorders affecting amino acid and protein metabolism. As dietary practice varies widely, we assessed their long-term prescribed dietary treatment against published guideline and studied plasma amino acids levels. We analyzed data from the first visit recorded in the European registry and network for intoxication type metabolic diseases (E-IMD, Chafea no. 2010 12 01). In total, 271 methylmalonic aciduria (MMA) and propionic aciduria (PA) and 361 UCD patients were included. Median natural protein prescription was consistent with the recommended daily allowance (RDA), plasma L-valine (57%), and L-isoleucine (55%) levels in MMA and PA lay below reference ranges. Plasma levels were particularly low in patients who received amino acid mixtures (AAMs-OAD) and L-isoleucine:L-leucine:L-valine (BCAA) ratio was 1.0:3.0:3.2. In UCD patients, plasma L-valine, L-isoleucine, and L-leucine levels lay below reference ranges in 18%, 30%, and 31%, respectively. In symptomatic UCD patients who received AAM-UCD, the median natural protein prescription lay below RDA, while their L-valine and L-isoleucine levels and plasma BCAA ratios were comparable to those in patients who did not receive AAM-UCD. Notably, in patients with ornithine transcarbamylase syndrome (OTC-D), carbamylphosphate synthetase 1 syndrome (CPS1-D) and hyperammonemia-hyperornithinemia-homocitrullinemia (HHH) syndrome selective L-citrulline supplementation resulted in higher plasma L-arginine levels than selective L-arginine supplementation. In conclusion, while MMA and PA patients who received AAMs-OAD had very low BCAA levels and disturbed plasma BCAA ratios, AAMs-UCD seemed to help UCD patients obtain normal BCAA levels. In patients with OTC-D, CPS1-D, and HHH syndrome, selective L-citrulline seemed preferable to selective L-arginine supplementation.

Published
2019

13. EPG5-related Vici syndrome defines a new group of multisystem disorders due to defects in membrane trafficking and autophagy

Author

BYRNE, S, U-KING-IM, J M, BODI, I, DIONISI-VICI, C, AL-GAZALI, L, AL-OWAIN, M, BROWN, N J, EL-GARHI, R, GERSHONI-BARUCH, R, FILLOUX, F, KAMATH, A, KOELKER, S, MANCHESTER, D, MANZUR, A, MANDEL, H, MEIN, R, MIYATA, R, PILZ, D, ROGERS, C C, RYAN, M, SAID, E, SCHARA, U, STEIN, A, SEWRY, C A, TRAVAN, L, WIJBURG, F A, YAU, S, FANTO, M, GAUTEL, M, and JUNGBLUTH, H

Published
2015

14. Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: First revision

Author

Forny, P., Hörster, F., Ballhausen, D., Chakrapani, A., Chapman, K.A., Dionisi-Vici, C., Dixon, M., Grünert, S.C., Grunewald, S., Haliloglu, G., Hochuli, M., Honzik, T., Karall, D., Martinelli, D., Molema, F., Sass, J.O., Scholl-Bürgi, S., Tal, G., Williams, M., Huemer, M., and Baumgartner, M.R.

Subjects
diagnosis and management, guidelines, inherited metabolic disease, methylmalonic acidaemia, propionic acidaemia
Abstract

Isolated methylmalonic acidaemia (MMA) and propionic acidaemia (PA) are rare inherited metabolic diseases. Six years ago, a detailed evaluation of the available evidence on diagnosis and management of these disorders has been published for the first time. The article received considerable attention, illustrating the importance of an expert panel to evaluate and compile recommendations to guide rare disease patient care. Since that time, a growing body of evidence on transplant outcomes in MMA and PA patients and use of precursor free amino acid mixtures allows for updates of the guidelines. In this article, we aim to incorporate this newly published knowledge and provide a revised version of the guidelines. The analysis was performed by a panel of multidisciplinary health care experts, who followed an updated guideline development methodology (GRADE). Hence, the full body of evidence up until autumn 2019 was re-evaluated, analysed and graded. As a result, 21 updated recommendations were compiled in a more concise paper with a focus on the existing evidence to enable well-informed decisions in the context of MMA and PA patient care.

Published
2021

16. Cystathionine β-synthase deficiency in the E-HOD registry-part I: pyridoxine responsiveness as a determinant of biochemical and clinical phenotype at diagnosis

Author

Kožich, V., Sokolová, J., Morris, A.A., Pavlíková, M., Gleich, F., Kölker, S., Krijt, J., Dionisi-Vici, C., Baumgartner, M.R., Janssen, M.C.H., Blom, H.J., and Huemer, M.

Subjects
Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]
Abstract

Contains fulltext : 245669.pdf (Publisher’s version ) (Open Access) Cystathionine β-synthase (CBS) deficiency has a wide clinical spectrum, ranging from neurodevelopmental problems, lens dislocation and marfanoid features in early childhood to adult onset disease with predominantly thromboembolic complications. We have analysed clinical and laboratory data at the time of diagnosis in 328 patients with CBS deficiency from the E-HOD (European network and registry for Homocystinurias and methylation Defects) registry. We developed comprehensive criteria to classify patients into four groups of pyridoxine responsivity: non-responders (NR), partial, full and extreme responders (PR, FR and ER, respectively). All groups showed overlapping concentrations of plasma total homocysteine while pyridoxine responsiveness inversely correlated with plasma/serum methionine concentrations. The FR and ER groups had a later age of onset and diagnosis and a longer diagnostic delay than NR and PR patients. Lens dislocation was common in all groups except ER but the age of dislocation increased with increasing responsiveness. Developmental delay was commonest in the NR group while no ER patient had cognitive impairment. Thromboembolism was the commonest presenting feature in ER patients, whereas it was least likely at presentation in the NR group. This probably is due to the differences in ages at presentation: all groups had a similar number of thromboembolic events per 1000 patient-years. Clinical severity of CBS deficiency depends on the degree of pyridoxine responsiveness. Therefore, a standardised pyridoxine-responsiveness test in newly diagnosed patients and a critical review of previous assessments is indispensable to ensure adequate therapy and to prevent or reduce long-term complications.

Published
2021

17. Delineating the neurological phenotype in children with defects in theECHS1orHIBCHgene

Author

Marti-Sanchez L, Baide-Mairena H, Marcé-Grau A, Pons R, Skouma A, López-Laso E, Sigatullina M, Rizzo C, Semeraro M, Martinelli D, Carrozzo R, Dionisi-Vici C, LUIS GONZÁLEZ GUTIÉRREZ-SOLANA, Correa-Vela M, Ortigoza-Escobar JD, Sánchez-Montañez Á, Vazquez É, Delgado I, Aguilera-Albesa S, Yoldi ME, Ribes A, Tort F, Pollini L, Galosi S, Leuzzi V, Tolve M, Pérez-Gay L, Aldamiz-Echevarría L, Del Toro M, Arranz A, Roelens F, Urreizti R, Artuch-Iriberri R, Alfons Macaya, and Pérez-Dueñas B

Subjects
valine catabolism, basal ganglia cavitation, ECHS1, methacrylate metabolites, HIBCH, Leigh syndrome, paroxysmal dystonia
Abstract

The neurological phenotype of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) and short-chain enoyl-CoA hydratase (SCEH) defects is expanding and natural history studies are necessary to improve clinical management. From 42 patients with Leigh syndrome studied by massive parallel sequencing, we identified five patients with SCEH and HIBCH deficiency. Fourteen additional patients were recruited through collaborations with other centres. In total, we analysed the neurological features and mutation spectrum in 19 new SCEH/HIBCH patients. For natural history studies and phenotype to genotype associations we also included 70 previously reported patients. The 19 newly identified cases presented with Leigh syndrome (SCEH, n = 11; HIBCH, n = 6) and paroxysmal dystonia (SCEH, n = 2). Basal ganglia lesions (18 patients) were associated with small cysts in the putamen/pallidum in half of the cases, a characteristic hallmark for diagnosis. Eighteen pathogenic variants were identified, 11 were novel. Among all 89 cases, we observed a longer survival in HIBCH compared to SCEH patients, and in HIBCH patients carrying homozygous mutations on the protein surface compared to those with variants inside/near the catalytic region. The SCEH p.(Ala173Val) change was associated with a milder form of paroxysmal dystonia triggered by increased energy demands. In a child harbouring SCEH p.(Ala173Val) and the novel p.(Leu123Phe) change, an 83.6% reduction of the protein was observed in fibroblasts. The SCEH and HIBCH defects in the catabolic valine pathway were a frequent cause of Leigh syndrome in our cohort. We identified phenotype and genotype associations that may help predict outcome and improve clinical management.

Published
2021

23. Long-term effects of medical management on growth and weight in individuals with urea cycle disorders

Author

Posset, R. (Roland), Garbade, S.F. (Sven), Gleich, F. (Florian), Gropman, A.L. (Andrea L.), Lonlay, P. (Pascale) de, Hoffmann, G.F. (Georg), Garcia-Cazorla, A. (Angeles), Nagamani, S.C.S. (Sandesh C. S.), Baumgartner, M.R. (Matthias), Schulze, A. (Andreas), Dobbelaere, D. (Dries), Yudkoff, M. (Marc), Kölker, S. (Stefan), Zielonka, M. (Matthias), Ah Mew, N. (Nicholas), Berry, S.A. (Susan A.), McCandless, S.E. (Shawn E.), Coughlin, C. (Curtis), Enns, G. (Gregory), Gallagher, R.C. (Renata C.), Burrage, L.C. (Lindsay C.), Seminara, J. (Jennifer), Harding, C.O. (Cary O.), Burgard, P. (Peter), Le Mons, C. (Cynthia), Merritt, J.L. (J. Lawrence), Stricker, T. (Tamar), Bedoyan, J. (Jirair), Berry, G.T. (Gerard T.), Diaz, G.A. (George A.), Wong, D. (Derek), Tuchman, M. (Mendel), Waisbren, S. (Susan), Weisfeld-Adams, J.D. (James D), Burlina, A.B. (Alberto), Leão Teles, E. (Elisa), Pedrón-Giner, C. (Consuelo), Lund, A.M. (Allan M.), Dionisi-Vici, C. (Carlo), Williams, M. (Monique), Mütze, U. (Ulrike), Karall, D. (Daniela), Blasco-Alonso, J. (Javier), Couce, M.L. (Maria L.), Sykut-Cegielska, J. (Jolanta), Augoustides-Savvopoulou, P. (Persa), Ruiz Gomez, A. (Angeles), Barić, I. (Ivo), Schiff, M. (Manuel), Chien, Y.-H. (Yin-Hsiu), Lindner, M. (Martin), Chabrol, B. (Brigitte), Skouma, A. (Anastasia), Zeman, J. (Jiri), Sokal, E. (Etienne), Santer, R. (Rene), Eyskens, F. (François), Freisinger, P. (Peter), Peña-Quintana, L. (Luis), Roland, D. (Dominique), Cortès-Saladelafont, E. (Elisenda), Djordjevic, M. (Maja), Posset, R. (Roland), Garbade, S.F. (Sven), Gleich, F. (Florian), Gropman, A.L. (Andrea L.), Lonlay, P. (Pascale) de, Hoffmann, G.F. (Georg), Garcia-Cazorla, A. (Angeles), Nagamani, S.C.S. (Sandesh C. S.), Baumgartner, M.R. (Matthias), Schulze, A. (Andreas), Dobbelaere, D. (Dries), Yudkoff, M. (Marc), Kölker, S. (Stefan), Zielonka, M. (Matthias), Ah Mew, N. (Nicholas), Berry, S.A. (Susan A.), McCandless, S.E. (Shawn E.), Coughlin, C. (Curtis), Enns, G. (Gregory), Gallagher, R.C. (Renata C.), Burrage, L.C. (Lindsay C.), Seminara, J. (Jennifer), Harding, C.O. (Cary O.), Burgard, P. (Peter), Le Mons, C. (Cynthia), Merritt, J.L. (J. Lawrence), Stricker, T. (Tamar), Bedoyan, J. (Jirair), Berry, G.T. (Gerard T.), Diaz, G.A. (George A.), Wong, D. (Derek), Tuchman, M. (Mendel), Waisbren, S. (Susan), Weisfeld-Adams, J.D. (James D), Burlina, A.B. (Alberto), Leão Teles, E. (Elisa), Pedrón-Giner, C. (Consuelo), Lund, A.M. (Allan M.), Dionisi-Vici, C. (Carlo), Williams, M. (Monique), Mütze, U. (Ulrike), Karall, D. (Daniela), Blasco-Alonso, J. (Javier), Couce, M.L. (Maria L.), Sykut-Cegielska, J. (Jolanta), Augoustides-Savvopoulou, P. (Persa), Ruiz Gomez, A. (Angeles), Barić, I. (Ivo), Schiff, M. (Manuel), Chien, Y.-H. (Yin-Hsiu), Lindner, M. (Martin), Chabrol, B. (Brigitte), Skouma, A. (Anastasia), Zeman, J. (Jiri), Sokal, E. (Etienne), Santer, R. (Rene), Eyskens, F. (François), Freisinger, P. (Peter), Peña-Quintana, L. (Luis), Roland, D. (Dominique), Cortès-Saladelafont, E. (Elisenda), and Djordjevic, M. (Maja)

Abstract

Low protein diet and sodium or glycerol phenylbutyrate, two pillars of recommended long-term therapy of individuals with urea cycle disorders (UCDs), involve the risk of iatrogenic growth failure. Limited evidence-based studies hamper our knowledge on the long-term effects of the proposed medical management in individuals with UCDs. We studied the impact of medical management on growth and weight development in 307 individuals longitudinally followed by the Urea Cycle Disorders Consortium (UCDC) and the European registry and network for Intoxication type Metabolic Diseases (E-IMD). Intrauterine growth of all investigated UCDs and postnatal linear growth of asymptomatic individuals remained unaffected. Symptomatic individuals were at risk of progressive growth retardation independent from the underlying disease and the degree of natural protein restriction. Growth impairment was determined by disease severity and associated with reduced or borderline plasma branched-chain amino acid (BCAA) concentrations. Liver transplantation appeared to have a beneficial effect on growth. Weight development remained unaffected both in asymptomatic and symptomatic individuals. Progressive growth impairment depends on disease severity and plasma BCAA concentrations, but cannot be predicted by the amount of natural protein intake alone. Future clinical trials are necessary to evaluate whether supplementation with BCAAs might improve growth in UCDs.

Published
2020
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24. Long-term effects of medical management on growth and weight in individuals with urea cycle disorders

Author

Posset, R, Garbade, SF, Gleich, F, Gropman, AL, de Lonlay, P, Hoffmann, GF, Garcia-Cazorla, A, Nagamani, SCS, Baumgartner, MR, Schulze, A, Dobbelaere, D, Yudkoff, M, Kölker, S, Zielonka, M, Ah Mew, N, Berry, SA, McCandless, SE, Coughlin, C, Enns, G, Gallagher, RC, Burrage, LC, Seminara, J, Harding, CO, Burgard, P, Le Mons, C, Merritt, JL, II, Stricker, T, Bedoyan, JK, Berry, GT, Diaz, GA, Wong, D, Tuchman, M, Waisbren, S, Weisfeld-Adams, JD, Burlina, AB, Leão Teles, E, Pedrón-Giner, C, Lund, AM, Dionisi-Vici, C, Williams, Monique, Mütze, U, Karall, D, Blasco-Alonso, J, Couce, ML, Sykut-Cegielska, J, Augoustides-Savvopoulou, P, Ruiz Gomez, A, Bari?, I, Schiff, M, Chien, YH, Lindner, M, Chabrol, B, Skouma, A, Zeman, J, Sokal, E, Santer, R, Eyskens, F, Freisinger, P, Peña-Quintana, L, Roland, D, Cortès-Saladelafont, E, Djordjevic, M, Posset, R, Garbade, SF, Gleich, F, Gropman, AL, de Lonlay, P, Hoffmann, GF, Garcia-Cazorla, A, Nagamani, SCS, Baumgartner, MR, Schulze, A, Dobbelaere, D, Yudkoff, M, Kölker, S, Zielonka, M, Ah Mew, N, Berry, SA, McCandless, SE, Coughlin, C, Enns, G, Gallagher, RC, Burrage, LC, Seminara, J, Harding, CO, Burgard, P, Le Mons, C, Merritt, JL, II, Stricker, T, Bedoyan, JK, Berry, GT, Diaz, GA, Wong, D, Tuchman, M, Waisbren, S, Weisfeld-Adams, JD, Burlina, AB, Leão Teles, E, Pedrón-Giner, C, Lund, AM, Dionisi-Vici, C, Williams, Monique, Mütze, U, Karall, D, Blasco-Alonso, J, Couce, ML, Sykut-Cegielska, J, Augoustides-Savvopoulou, P, Ruiz Gomez, A, Bari?, I, Schiff, M, Chien, YH, Lindner, M, Chabrol, B, Skouma, A, Zeman, J, Sokal, E, Santer, R, Eyskens, F, Freisinger, P, Peña-Quintana, L, Roland, D, Cortès-Saladelafont, E, and Djordjevic, M

Published
2020

25. Early neurodevelopmental characterization in children with cobalamin C/defect

Author

Ricci, Daniela, Martinelli, Daniela, Ferrantini, Gloria, Lucibello, Simona, Gambardella, Maria Luigia, Olivieri, Giorgia, Chieffo, Daniela Pia Rosaria, Battaglia, Domenica Immacolata, Diodato, D., Iarossi, G., Donati, A. M., Dionisi-Vici, C., Battini, Roberta, Mercuri, Eugenio Maria, Ricci D., Martinelli D., Ferrantini G., Lucibello S., Gambardella M., Olivieri G., Chieffo D., Battaglia D. (ORCID:0000-0003-0491-4021), Battini R., Mercuri E. M. (ORCID:0000-0002-9851-5365), Ricci, Daniela, Martinelli, Daniela, Ferrantini, Gloria, Lucibello, Simona, Gambardella, Maria Luigia, Olivieri, Giorgia, Chieffo, Daniela Pia Rosaria, Battaglia, Domenica Immacolata, Diodato, D., Iarossi, G., Donati, A. M., Dionisi-Vici, C., Battini, Roberta, Mercuri, Eugenio Maria, Ricci D., Martinelli D., Ferrantini G., Lucibello S., Gambardella M., Olivieri G., Chieffo D., Battaglia D. (ORCID:0000-0003-0491-4021), Battini R., and Mercuri E. M. (ORCID:0000-0002-9851-5365)

Abstract

Cobalamin C (cblC) defect is the most common inherited disorder of cobalamin metabolism. Developmental delay, behavioral problems, and maculopathy are common, but they have not been systematically investigated. The aim of this study was to define early neurodevelopment in cblC patients and the possible contribution of different factors, such as mode of diagnosis, age at diagnosis, presence of brain lesions and epilepsy. Children up to the age of 4 years with a visual acuity ≥1/10 were evaluated using the Griffiths' Mental Development Scales. Eighteen children were enrolled (age range 12-48 months). Four were diagnosed by newborn screening (NBS); in the others mean age at diagnosis was 3.5 months (range 0.3-18 months). Eight had seizures: three in the first year, and five after the second year of life. Fourteen had brain lesions on magnetic resonance imaging (MRI). Neurovisual assessment evidenced low visual acuity (<3/10) in 4/18. NBS diagnosed patients had higher general and subquotients neurodevelopmental scores, normal brain MRI, and no epilepsy. The others showed a progressive reduction of the developmental quotient with age and language impairment, which was evident after 24 months of age. Our findings showed a progressive neurodevelopmental deterioration and a specific fall in language development after 24 months in cblC defect. The presence of brain lesions and epilepsy was associated with a worst neurodevelopmental outcome. NBS, avoiding major disease-related events and allowing an earlier treatment initiation, appeared to have a protective effect on the development of brain lesions and to promote a more favorable neurodevelopment.

Published
2020

37. Transatlantic combined and comparative data analysis of 1095 patients with urea cycle disordersA successful strategy for clinical research of rare diseases

Author

Posset R, Garbade SF, Boy N, Burlina AB, Dionisi-Vici C, Dobbelaere D, Garcia-Cazorla A, de Lonlay P, Teles EL, Vara R, Ah Mew N, Batshaw ML, Baumgartner MR, McCandless S, Seminara J, Summar M, Hoffmann GF, Kölker S, Burgard P, and Additional individual contributors of the UCDC and the E-IMD consortium

Abstract

To improve our understanding of urea cycle disorders (UCDs) prospectively followed by two North American (NA) and European (EU) patient cohorts.

Published
2019

49. Phenotype, treatment practice and outcome in the cobalamin-dependent remethylation disorders and MTHFR deficiency: data from the E-HOD registry

Author

Huemer, M. Diodato, D. Martinelli, D. Olivieri, G. Blom, H. Gleich, F. Kölker, S. Kožich, V. Morris, A.A. Seifert, B. Froese, D.S. Baumgartner, M.R. Dionisi-Vici, C. Martin, C.A. Baethmann, M. Ballhausen, D. Blasco-Alonso, J. Boy, N. Bueno, M. Burgos Peláez, R. Cerone, R. Chabrol, B. Chapman, K.A. Couce, M.L. Crushell, E. Dalmau Serra, J. Diogo, L. Ficicioglu, C. García Jimenez, M.C. García Silva, M.T. Gaspar, A.M. Gautschi, M. González-Lamuño, D. Gouveia, S. Grünewald, S. Hendriksz, C. Janssen, M.C.H. Jesina, P. Koch, J. Konstantopoulou, V. Lavigne, C. Lund, A.M. Martins, E.G. Meavilla Olivas, S. Mention, K. Mochel, F. Mundy, H. Murphy, E. Paquay, S. Pedrón-Giner, C. Ruiz Gómez, M.A. Santra, S. Schiff, M. Schwartz, I.V. Scholl-Bürgi, S. Servais, A. Skouma, A. Tran, C. Vives Piñera, I. Walter, J. Weisfeld-Adams, J. the EHOD consortium

Abstract

Aim: To explore the clinical presentation, course, treatment and impact of early treatment in patients with remethylation disorders from the European Network and Registry for Homocystinurias and Methylation Defects (E-HOD) international web-based registry. Results: This review comprises 238 patients (cobalamin C defect n = 161; methylenetetrahydrofolate reductase deficiency n = 50; cobalamin G defect n = 11; cobalamin E defect n = 10; cobalamin D defect n = 5; and cobalamin J defect n = 1) from 47 centres for whom the E-HOD registry includes, as a minimum, data on medical history and enrolment visit. The duration of observation was 127 patient years. In 181 clinically diagnosed patients, the median age at presentation was 30 days (range 1 day to 42 years) and the median age at diagnosis was 3.7 months (range 3 days to 56 years). Seventy-five percent of pre-clinically diagnosed patients with cobalamin C disease became symptomatic within the first 15 days of life. Total homocysteine (tHcy), amino acids and urinary methylmalonic acid (MMA) were the most frequently assessed disease markers; confirmatory diagnostics were mainly molecular genetic studies. Remethylation disorders are multisystem diseases dominated by neurological and eye disease and failure to thrive. In this cohort, mortality, thromboembolic, psychiatric and renal disease were rarer than reported elsewhere. Early treatment correlates with lower overall morbidity but is less effective in preventing eye disease and cognitive impairment. The wide variation in treatment hampers the evaluation of particular therapeutic modalities. Conclusion: Treatment improves the clinical course of remethylation disorders and reduces morbidity, especially if started early, but neurocognitive and eye symptoms are less responsive. Current treatment is highly variable. This study has the inevitable limitations of a retrospective, registry-based design. © 2018 SSIEM

Published
2018

50. Decreased plasma l-arginine levels in organic acidurias (MMA and PA) and decreased plasma branched-chain amino acid levels in urea cycle disorders as a potential cause of growth retardation: Options for treatment

Author

Molema, Femke, primary, Gleich, Florian, additional, Burgard, Peter, additional, van der Ploeg, Ans T., additional, Summar, Marshall L., additional, Chapman, Kimberly A., additional, Lund, Allan M., additional, Rizopoulos, Dimitris, additional, Kölker, Stefan, additional, Williams, Monique, additional, Hörster, F., additional, Jelsig, A.M., additional, de Lonlay, P., additional, Wijburg, F.A., additional, Bosch, A., additional, Freisinger, P., additional, Posset, R., additional, Augoustides-Savvopoulou, P., additional, Avram, P., additional, Deleanu, C., additional, Baumgartner, M.R., additional, Häberle, J., additional, Blasco-Alonso, J., additional, Burlina, A.B., additional, Rubert, L., additional, Cazorla, A. Garcia, additional, Saladelafont, E. Cortes I., additional, Dionisi-Vici, C., additional, Martinelli, D., additional, Dobbelaere, D., additional, Mention, K., additional, Grünewald, S., additional, Chakrapani, A., additional, Hwu, Wuh-Liang, additional, Chien, Yin-Hsiu, additional, Lee, Ni-Chung, additional, Karall, D., additional, Scholl-Bürgi, S., additional, De Laet, C., additional, Matsumoto, S., additional, de Meirleir, L., additional, Schiff, M., additional, Peña-Quintana, L., additional, Djordjevic, M., additional, Sarajlija, A., additional, Sykut-Cegielska, J., additional, Wisniewska, A., additional, Leao-Teles, E., additional, Alves, S., additional, Vara, R., additional, Vives-Pinera, I., additional, Gil-Ortega, D., additional, Morris, A., additional, Zeman, J., additional, Honzik, T., additional, Chabrol, B., additional, Arnaudo, F., additional, Cano, A., additional, Thompson, N., additional, Eyskens, F., additional, Lindner, M., additional, Lüsebrink, N., additional, Jalan, A., additional, Sokal, E., additional, Legros, V., additional, Nassogne, M.C., additional, and Barić, I., additional

Published
2019
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