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This expert-opinion-based document was prepared by a group of specialists in pediatric inherited metabolic diseases and infectious diseases including administrative board members of Turkish Society for Pediatric Nutrition and Metabolism to provide guidance for the care of children with lysosomal storage disorders (LSDs) during the COVID-19 pandemic in Turkey. The experts reached consensus on key areas of focus regarding COVID-19-based risk status in relation to intersecting immune-inflammatory mechanisms and disease patterns in children with LSDs, diagnostic virus testing, particularly preventive measures and priorities during the pandemic, routine screening and diagnostic interventions for LSDs, psychological and socioeconomic impact of confinement measures and quarantines and optimal practice patterns in managing LSDs and/or COVID-19. The participating experts agreed on the intersecting characteristics of immune-inflammatory mechanisms, end-organ damage and prognostic biomarkers in LSD and COVID-19 populations, emphasizing the likelihood of enhanced clinical care when their interaction is clarified via further studies addressing certain aspects related to immunity, lysosomal dysfunction and disease pathogenesis. In the context of the current global COVID-19 pandemic, this expert-opinion-based document provides guidance for the care of children with LSDs during the COVID-19 pandemic based on the recent experience in Turkey.

Abstract Background Sanfilippo syndrome type B (Sanfilippo B) belongs to a group of rare lysosomal storage diseases characterized by progressive cognitive decline from an early age, acute hyperactivity, and concomitant somatic symptoms. Caregivers face a unique set of challenges related to the complex nature of Sanfilippo B, but the burden and impact on quality of life (QoL) of caregivers is poorly defined and best practice guidance for clinicians is lacking. Methods An international clinical advisors meeting was convened to discuss key aspects of caregiver burden associated with Sanfilippo B based on findings from qualitative and quantitative research undertaken to identify and quantify the nature and impact of the disease on patients and caregivers. Results Providing care for patients with Sanfilippo B impinges on all aspects of family life, evolving as the patient ages and the disease progresses. Important factors contributing toward caregiver burden include sleep disturbances, impulsive and hyperactive behavior, and communication difficulties. Caregiver burden remained high throughout the life of the patient and, coupled with the physical burden of daily care, had a cumulative impact that generated significant psychological stress. Conclusion A Sanfilippo-specific QoL questionnaire is needed that is directed at caregiver needs and burden and best practice management of these domains.

Fabry disease is a rare, X-linked disease, caused by the deficiency of lysosomal and #945;-galactosidase. Clinical fetaures are; acroparesthesia, unexplained fever, hypohidrosis and angiokeratomas. Untreated cases die early from cardiac complications, renal insuffiency or stroke. Currently there is no cure for Fabry disease, enzyme replacement therapy is the only choice in this progressive disease. A 9-year-old boy admitted to the Dermatology Clinic with reddish papular skin lesions, joint pain and anhydrosis. Hystological examination of the skin biopsy revealed angiokeratoma. There was no renal dysfunction or proteinuria. Biochemical confirmation of Fabry disease was made by determining the deficient leukocyte and #945;-galactosidase activity. Subsequently, the patient's molecular analysis was identified a novel nonsense mutation c. 785G>T in the GLA gene. Enzyme replacement therapy with agalsidase beta was started. He is on enzyme replacement therapy for 8 years, significant improvement was obtained in severity and frequency of pain crisis and fatigue. We report this case to emphasize the importance of early diagnosis of Fabry disease restricted to dermatological findings, especially before renal and cardiac involvement occurs, while enzyme replacement therapy is now available. Also this patient is one of the first Fabry patients under enzyme replacement therapy in Turkey. [Cukurova Med J 2015; 40(Suppl 1): 156-160]

In newborns, hyperammonemia leads to encephalopathy which is usually characterized by vomiting, hypotonia, lethargy, seizures and coma. Continuous venovenous hemodiafiltration (CVVHDF) is a modality choice to treat acute decompensation in hyperammonemia. Here we report three newborn patients with hypotonia, convulsion and hyperammonaemia. In the first three days of life, their serum ammonia levels were 4609, 1023 and 1949 and #61549;g/ml. They were successfully treated with CVVHDF and serum ammonia levels subsequently decreased to 268, 164 and 65 and #61549;g/ml in the first 24 hours of treatment. The complications were mild hypothermia and anemia. [Cukurova Med J 2015; 40(Suppl 1): 161-166]

Purpose: Osteogenesis imperfecta is an inherited disorder of connective tissue. Children with this condition suffer from recurrent fractures, deformities, osteoporosis and pain. Over the recent years, pamidronate became the standard treatment choice. However the optimal dose and interval have not been defined yet. The main of this study was to compare of two different pamidronate regime. Materials and Methods: 12 patients aged 42.3 +/- 37.4 months were studied. At the beginning patients had received pamidronate infusion at a dose of 1.5 mg/kg/day once, every two months with duration of 23.5 +/- 9.0 months (first protocol), than switched to a dose of 1mg/kg/day for three consecutive days, every three months with duration of 18.5 +/- 5.1 months (second protocol). The bone mineral density Z-score was evaluated yearly. Results: Annual fracture rate decreased from 6.3 +/- 5.5 to 1.1 +/- 1.3 (p=0.001) in the first and from 1.1 +/- 1.3 to 0.0 +/- 0.0 (p

Purpose: The main objective of this study was to compare the treatments of calcitonin and pamidronate by clinical, biochemical, and radiological findings in children with osteogenesis imperfecta and evaluate the efficiency of pamidronate treatment. Patients and methods: A total of 12 patients, aged 41±38 (1-120) months were studied. Group 1 was consisted of six patients who had received intranasal calcitonin at a dosage of 4-6 U/kg three times a week before switching to pamidronate treatment. Group 2 was also consisted of six patients who had received only pamidronate infusion at a dosage of 0.5-2 mg/kg every two months. Results: Annual fracture rates decreased from 2.72 ± 0.80 to 0.40 ± 0.70 (p0.05), and from -3.08 ± -0.61 to -2.29 ± -0.56 in pamidronate group. The difference between the Z-scores of bone mineral density after calcitonin and pamidronate treatments was statistically significant (p

Glutaric aciduria type I is an autosomal recessive inherited disorder caused by the deficiency of glutaryl CoA dehydrogenase. The incidence of the disease is 1/100.000. Glutaryl CoA dehydrogenase gene is located on locus 19p13.2. More than 200 mutations have been described for this gene. Most common mutation in the population is C1240T. Clinical symptoms included neurological regression complications such as loss of sucking and swallowing reflexes choreoathetosis, seizures, rigidity and opisthotonos. In treatment high-carbohydrate, low-protein diet and carnitine is given. We would like to report this interesting case in order to present a new mutation for glutaric aciduria type I. [Cukurova Med J 2013; 38(4.000): 809-812]

Multiple sulfatase deficiency is biochemically characterized by the accumulation of sulfated lipids and acid mucopolysaccharides. The gene sulfatase-modifying factor 1 (SUMF1), recently identified, encodes the enzyme responsible for post-translational modification of a cysteine residue, which is essential for the activity of sulfatases. We describe clinical findings and mutation analysis of four patients. The patients presented with hypotonia, developmental delay, coarse face, ichthyosis, and hepatosplenomegaly. The diagnosis was made through clinical findings, enzymatic assays, and mutation analysis. We were detected to be homozygous for a novel missense mutation c. 739G > C causing a p.G247R amino acid substitution in the SUMF1 protein.

Aim:Alkaptonuria (AKU) is an autosomal recessively inherited disease caused by a deficiency of homogentisate 1,2-dioxygenase. This enzyme converts homogentisic acid (HGA) into maleylacetoacetic acid in the tyrosine degradation pathway. The presence of HGA in urine, ochronosis (bluish-black pigmentation in connective tissues) and arthritis of the spine and the other large joints are the three major features of AKU. Nitisinone and a tyrosine-restricted diet are the treatment options. In this study, we evaluated the demographic and clinical characteristics and also the mutations of our AKU patients.Materials and Methods:This retrospective single centre study included 36 patients who were diagnosed as AKU between the years of 2002 and 2017 Çukurova University Faculty of Medicine, Department of Pediatrics, Division of Metabolism and Nutrition.Results:Thirty six AKU patients were included (17 female, 19 male) in our study. The mean age of the patients was 9.3±13.4 years (3 months-54 years). The major complaints were darkening of the urine (100%), ochronosis (11.1%), arthralgia (16.7%) and arthritis (8.1%). Darkening of the urine was firstly recognized at the age of 8.89±16.9 months (1-84 months). Eighteen (86%) patients had homozygous and 3 (14%) patients had compound heterozygous mutations in the HGD gene.Conclusion:AKU was the first inherited metabolic disease defined. The three main features are; darkening of the urine at birth which is followed by ochronosis (blue-dark pigmentation) clinically visible in the ear and alae of the nose and finally a severe ochronotic arthropathy of the spine and large joints at around the age of 50 years. Here we report on the clinical and genetic features of our patients at various ages.

Typical features of Netherton syndrome are congenital ichthyosiform erythroderma, atopic diathesis and trichorrhexis nodosa. Here in this report, we present a case with congenital ichthyosis with atopy presenting later. We wanted to discuss the importance of whole exome sequencing to diagnose the atypical presentations of common syndromes.

Background: Tyrosinemia type I is an autosomal recessively inherited metabolic disease of tyrosine metabolism due to the deficiency of fumarylacetoacetate hydrolase. Clinical manifestations include hepatic failure, cirrhosis, hepatocellular carcinoma, renal fanconi syndrome, and neurologic crisis. With the introduction of 2-(2-nitro-4-trifluoro-methylbenzyol)-1.3 cyclohexanedione (NTBC) treatment, the prognosis improved with reduced rate of complications. Case Report: Here, we report a 6-year-old girl with tyrosinemia type I who discontinued NTBC treatment six months prior to admission, presenting with complaints of abdominal pain, vomiting, anorexia, weakness, and restlessness, suggesting the clinical status of neurologic crisis. Further laboratory and radiologic evaluation revealed that indeed this is a pancreatitis. Conclusion: We report this case as tyrosinemia type I and pancreatitis was reported only in one case in the literature, emphasizing confusing clinical signs of neurological crisis, and pancreatitis in tyrosinemia type I.

Amaç: Osteogenezis imperfekta bağ dokusunun kalıtsal bir hastalığıdır. Bu durumdaki çocuklar tekrarlayan kırıklar, deformiteler, osteoporosis ve ağrıdan yakınırlar. Son yıllarda pamidronat standart tedavi tercihi olmuştur. Ancak, optimal doz ve aralık henüz tam olarak belirlenmemiştir. Bu çalışmada amaç, iki farklı pamidronat tedavi rejiminin karşılaştırılmasıdır. Materyal ve Metod: Yaşları 42.3 ± 37.4 ay arasında değişen toplam 12 hastada yapıldı. Başlangıçta her iki ayda bir defa 1.5 mg/kg/gün dozunda 23.5 ± 9.0 ay pamidromat infüzyonu uygulandı (ilk protokol), daha sonra üçer aylık aralarla 3 gün üstüste 1 mg/kg/gün 18.5 ± 5.1 ay dozuna geçildi (ikinci protokol). Kemik mineral dansitesi z-skoru yıllık değerlendirildi. Bulgular: Yıllık kırık oranı ilk protokolde 6.3 ± 5.5"den 1.1 ± 1.3"e (p=0.001), ikinci protokolde 1.1 ± 1.3"den 0.0 ± 0.0"a (p

Amaç: Bu çalışmanın temel amacı osteogenezis imperfekta olan çocuklarda klinik, biyokimyasal ve radyolojik bulgular ile pamidronat ve kalsitonin tedavisinin karşılaştırılması ve pamidronat tedavisinin etkinliğinin değerlendirilmesidir. Materyal ve Metod: Yaşları 41±38 (1-120) ay arasında değişen toplam 12 hasta çalışmaya alındı. Grup 1 pamidronat tedavisine geçmeden önce 4-6 U/kg haftada üç defa intranazal kalsitonin tedavisi alan altı hasta oluşturdu. Grup 2, iki ayda bir sadece tek doz 0.5-2 mg/kg dozunda pamidronat alan altı hasta idi. Bulgular: Yıllık kırık oranları Grup 1"de 2.72 ± 0.80"den 0.40 ± 0.70"e (p

Glutarik asidüri tip I glutaril KoA dehidrogenaz enziminin eksikliğine bağlı olarak gelişen ve otozomal resesif olarak kalıtılan bir metabolik hastalıktır. İnsidansı yaklaşık 1/ 100,000 dir. Glutaril KoA dehidrogenaz enziminin geni kromozom 19p13.2 dedir. Bu gende 200 farklı mutasyon tanımlanmıştır. Toplumda en sık görülen mutasyon C1240 T dir. Mutasyon tipi hastalığın fenotipini etkilemekle beraber aralarında kesin bir ilişki bulunamamıştır. Klinikte makrosefali, emme ve yutma reflekslerinin kaybolması, oturamama, koreatetoz, nöbetler, rijidite ve opistotonus gibi nörolojik regresyon bulguları vardır. Tedavide yüksek karbonhidratlı, düşük proteinli diyet ve karnitin verilir. Bizde glutarik asidüri tip I nedeniyle takibimize giren bir hastada daha önce tanımlanmamış bir mutasyonu saptadığımız için ilginç bularak bildirdik.

This review by a panel of pediatric metabolic disease specialists aimed to provide a practical and implementable guidance document to assist clinicians in best clinical practice in terms of recognition, diagnosis and management of patients with acid sphingomyelinase deficiency (ASMD). The participating experts consider the clinical suspicion of ASMD by the physician to be of utmost importance in the prevention of diagnostic delay and strongly suggest the use of a diagnostic algorithm including/starting with dried blood spots assay in the timely diagnosis of ASMD in patients presenting with hepatosplenomegaly and a need for increased awareness among physicians in this regard to consider ASMD in the differential diagnosis. In anticipation of the introduction of enzyme replacement therapy, raising awareness of the disease among physicians to prevent diagnostic delay and further investigation addressing natural history of ASMD across the disease spectrum, potential presenting characteristics with a high index of suspicion, as well as biomarkers and genotype-phenotype correlations suggestive of poor prognosis seem important in terms of implementation of best practice patterns.

Purpose: We investigated the neurological outcome of 38 late-diagnosed phenylketonuria patients with magnetic resonance imaging (MRI), electroencephalography (EEG), visual evoked potentials (VEP), intelligence quotients (IQ) and examined the correlation of these parameters with the age and the plasma phenylalanine levels of patients at diagnosis. Material and Methods: Thirty-eight late-diagnosed classic phenylketonuria patients were enrolled in the study. Plasma phenylalanine levels were measured by spectrofluorometric method. MRI was evaluated by a pediatric neuroradiologist. Ankara developmental screening inventory (ADSI) and Wechsler intelligence scale for Turkish children (WISC-R) test were performed to detect IQ scores. Porteus Mazo test adapted for Turkish children intelligence test were performed to all children. The EEG of all patients were recorded. VEP was used to measure the electrical activity in the brain to visual stimulus. Results: The high plasma phenylalanine levels and late-diagnosis were associated with low IQ scores, pathological EEG, and pathological VEP patterns. High PA levels were also associated with more serious white matter signal abnormalities. Conclusion: Our results demonstrated the impact of early diagnosis and low levels of phenylalanine at diagnosis on the intellectual, neurological development and visual outcomes. [Cukurova Med J 2016; 41(1.000): 21-27]

Objective: The aim of this study was to elucidate the role of adiponectin, leptin, TNF-α and IL-6 on the early detection of the microvascular complications of type I diabetes. Materials and Methods: A total of 88 children were included in the study. There were 60 type I diabetic patients and 28 healthy control children. Results: The gender, age, weight, height, BMI and puberty status characteristics were similar in the patient and control groups (p>0.05). The serum leptin, TNF-α and IL-6 levels were similar between the patient and control groups (p>0.05) and the only difference was in the serum adiponectin level which was higher in the patient group (p:0.042). We also found no association between the adiponectin, leptin, TNF-α and IL-6 levels and diabetes duration (p>0.05). Leptin was high in the pubertal period (p:0.016), while adiponectin TNF-α and IL-6 levels were similar in the prepubertal and pubertal periods (p>0.05). The serum leptin level was high in microalbuminuria patients (p0.05). The serum adiponectin level was lower in diabetic retinopathy patients (p:0.003), while the serum leptin level was higher (p:0.003). The TNF-α and IL-6 levels were similar in patients with and without retinopathy (p>0.05). Conclusion: We found increased serum adinopectin levels in children and adolescents with type I diabetes mellitus and low levels in diabetic retinopathy patients. Patients with low serum adiponectin levels and high leptin levels should be more closely monitored for chronic complication development and better metabolic control should be aimed for.