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Background In Europe, dietary management of isovaleric acidemia (IVA) may vary widely. There is limited collective information about dietetic management. Aim To describe European practice regarding the dietary management of IVA, prior to the availability of the E-IMD IVA guidelines (E-IMD 2014). Methods A cross-sectional questionnaire was sent to all European dietitians who were either members of the Society for the Study of Inborn Errors of Metabolism Dietitians Group (SSIEM-DG) or whom had responded to previous questionnaires on dietetic practice (n = 53). The questionnaire comprised 27 questions about the dietary management of IVA. Results Information on 140 patients with IVA from 39 centres was reported. 133 patients (38 centres) were given a protein restricted diet. Leucine-free amino acid supplements (LFAA) were routinely used to supplement protein intake in 58% of centres. The median total protein intake prescribed achieved the WHO/FAO/UNU [2007] safe levels of protein intake in all age groups. Centres that prescribed LFAA had lower natural protein intakes in most age groups except 1 to 10 y. In contrast, when centres were not using LFAA, the median natural protein intake met WHO/FAO/UNU [2007] safe levels of protein intake in all age groups. Enteral tube feeding was rarely prescribed. Conclusions This survey demonstrates wide differences in dietary practice in the management of IVA across European centres. It provides unique dietary data collectively representing European practices in IVA which can be used as a foundation to compare dietary management changes as a consequence of the first E-IMD IVA guidelines availability., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Tyrosinaemia type 1 is a rare inherited metabolic disease caused by an enzyme defect in the tyrosine degradation pathway. It is treated using nitisinone and a low-protein diet. In a workshop in 2013, a group of nutritional specialists from Germany, Switzerland and Austria agreed to advocate a simplified low-protein diet and to allow more natural protein intake in patients with tyrosinaemia type 1. This retrospective study evaluates the recommendations made at different treatment centers and their impact on clinical symptoms and metabolic control. Methods: For this multicenter study, questionnaires were sent to nine participating treatment centers to collect data on the general therapeutic approach and data of 47 individual patients treated by those centers. Results: Dietary simplification allocating food to 3 categories led to increased tyrosine and phenylalanine blood concentrations without weighing food. Phenylalanine levels were significantly higher in comparison to a strict dietary regimen whereas tyrosine levels in plasma did not change. Non-inferiority was shown for the simplification and liberalization of the diet. Compliance with dietary recommendations was higher using the simplified diet in comparison to the stricter approach. Age correlates negatively with compliance. Conclusions: Simplification of the diet with increased natural protein intake based on three categories of food may be implemented in the diet of patients with tyrosinaemia type 1 without significantly altering metabolic control. Patient compliance is strongly influencing tyrosine blood concentrations. A subsequent prospective study with a larger sample size is necessary to get a better insight into the effect of dietary recommendations on metabolic control.

Dietary management of 418 adult patients with galactosaemia (from 39 centres/12 countries) was compared. All centres advised lactose restriction, 6 restricted galactose from galactosides +/- fruits and vegetables and 12 offal. 38% (n = 15) relaxed diet by: 1) allowing traces of lactose in manufactured foods (n = 13) or 2) giving fruits, vegetables and galactosides (n = 2). Only 15% (n = 6) calculated dietary galactose. 32% of patients were lost to dietetic follow-up. In adult galactosaemia, there is limited diet relaxation. (C) 2015 Elsevier Inc. All rights reserved.

Background: There is no published data comparing dietary management of urea cycle disorders (UCD) in different countries.Methods: Cross-sectional data from 41 European Inherited Metabolic Disorder (IMD) centres (17 UK, 6 France, 5 Germany, 4 Belgium, 4 Portugal, 2 Netherlands, 1 Denmark, 1 Italy, 1 Sweden) was collected by questionnaire describing management of patients with UCD on prescribed protein restricted diets.Results: Data for 464 patients: N-acetylglutamate synthase (NAGS) deficiency, n = 10; carbamoyl phosphate synthetase (CPS1) deficiency, n = 29; ornithine transcarbamoylase (OTC) deficiency, n = 214; citrullinaemia, n = 108; argininosuccinic aciduria (ASA), n = 80; arginase deficiency, n = 23 was reported. The majority of patients (70%; n = 327) were aged 0-16 y and 30% (n = 137) >16 y. Prescribed median protein intake/kg body weight decreased with age with little variation between disorders. The UK tended to give more total protein than other European countries particularly in infancy. Supplements of essential amino acids (EAA) were prescribed for 38% [n = 174] of the patients overall, but were given more commonly in arginase deficiency (74%), CPS (48%) and citrullinaemia (46%). Patients in Germany (64%), Portugal (67%) and Sweden (100%) were the most frequent users of EAA. Only 18% [n = 84] of patients were prescribed tube feeds, most commonly for CPS (41%); and 21% [n = 97] were prescribed oral energy supplements.Conclusions: Dietary treatment for UCD varies significantly between different conditions, and between and within European IMD centres. Further studies examining the outcome of treatment compared with the type of dietary therapy and nutritional support received are required. (C) 2013 Elsevier Inc. All rights reserved.

A controlled long-term study was performed to assess the neurological and neuropsychological performance in adult patients with early-treated phenylketonuria (PKU).We investigated 57 patients with early-treated classical PKU aged 19 to 41 years (mean age 31 years) and 46 matched healthy controls, matched for age and socioeconomic status. Patients and controls were assessed for their intelligence quotient (IQ), and attention and information-processing abilities. Magnetic resonance imaging (MRI) of the brain was performed in all patients. Neuropsychological assessments and MRI were repeated at a five-year-follow-up.In the five-year interval IQ, information processing and attention of patients and controls remained constant. At both assessment times the IQ scores were significantly lower in patients compared to controls. Older adult patients (32 years) showed poorer information processing and attention at both assessment times compared to young adult patients (32 years) and controls. IQ, information processing and attention showed no correlation to imaging results but were significantly correlated to blood phenylalanine (Phe) levels in patients' childhood and adolescence, and Phe levels had been higher in the adolescent years of older adult patients.Cognitive performance in adult patients with early-treated PKU does not seem to be subject to deterioration observable in a five-year interval. Neuropsychological assessment in adults with PKU revealed neurocognitive impairment particularly in older adult patients. This seems to refer to an early relaxation of diet that was recommended when the older patients were adolescents. Results indicate a benefit of dietary control during adolescence in PKU.

Deficiency of propionyl CoA carboxylase (PCC), a dodecamer of alpha and beta subunits, causes inherited propionic acidemia. We have studied, at the molecular level, PCC in 54 patients from 48 families comprised of 96 independent alleles. These patients of various ethnic backgrounds came from research centers and hospitals in Germany, Austria and Switzerland. The thorough clinical characterization of these patients was described in the accompanying paper (Grünert et al. 2012). In all 54 patients, many of whom originated from consanguineous families, the entire PCCB gene was examined by genomic DNA sequencing and in 39 individuals the PCCA gene was also studied. In three patients we found mutations in both PCC genes. In addition, in many patients RT-PCR analysis of lymphoblast RNA, lymphoblast enzyme assays, and expression of new mutations in E.coli were carried out. Eight new and eight previously detected mutations were identified in the PCCA gene while 15 new and 13 previously detected mutations were found in the PCCB gene. One missense mutation, p.V288I in the PCCB gene, when expressed in E.coli, yielded 134% of control activity and was consequently classified as a polymorphism in the coding region. Numerous new intronic polymorphisms in both PCC genes were identified. This study adds a considerable amount of new molecular data to the studies of this disease.

Background: There appears little consensus concerning protein requirements in phenylketonuria (PKU). Methods: A questionnaire completed by 63 European and Turkish IMD centres from 18 countries collected data on prescribed total protein intake (natural/intact protein and phenylalanine-free protein substitute [PS]) by age, administration frequency and method, monitoring, and type of protein substitute. Data were analysed by European region using descriptive statistics. Results: The amount of total protein (from PS and natural/intact protein) varied according to the European region. Higher median amounts of total protein were prescribed in infants and children in Northern Europe (n = 24 centres) (infants 2-3 g/kg/day; 1-3 years of age, >2-3 g/kg/day; 4-10 years of age, >1.5-2.5 g/kg/day) and Southern Europe (n = 10 centres) (infants 2-2.5 g/kg/day; 4-10 years of age, >1.5-2 g/kg/day) and with Western Europe (n = 25 centres) giving the least (infants 2-2.5 g/kg/day, 1-3 years of age, 1.5-2 g/kg/day; 4-10 years of age, 1-1.5 g/kg/day). Total protein prescription was similar in patients aged >10 years (1-1.5 g/kg/day) and maternal patients (1-1.5 g/kg/day). Conclusions: The amounts of total protein prescribed varied between European countries and appeared to be influenced by geographical region. In PKU, all gave higher than the recommended 2007 WHO/FAO/UNU safe levels of protein intake for the general population. (C) 2015 Elsevier Inc. All rights reserved.

Steht die Diagnose Zoliakie erst einmal fest, bedeutet dies fur den Betroffenen eine lebenslange Umstellung auf eine glutenfreie Ernahrung. Chemisch betrachtet ist, Gluten ein Oberbegriff fur die alkoholloslichen Prolaminfraktionen der Getreideeiweise aus Weizen, Gerste, Roggen und Hafer. Gluten ist ernahrungsphysiologisch gesehen kein hochwertiges Eiweis, der Verzicht fuhrt zu keinerlei Mangelerscheinung. Lebensmitteltechnisch betrachtet, bietet Gluten eine Fulle von positiven Eigenschaften, die in der Lebensmittelindustrie nicht wegzudenken sind. So hat es gute backtechnologische Eigenschaften und wird zur Frischhaltung von Gebacken genutzt, um nur einige Vorteile zu nennen. Fur Zoliakiebetroffene bedeutet dies, dass es nicht ausreicht, glutenhaltige Getreide, deren Mehle und Zubereitungen zu vermeiden, sondern dass jede Speise, jedes Fertiggericht kritisch hinterfragt werden mussen. Gute Beratung, Aufklarung und Schulung des Betroffenen und der Familie durch eine(n) erfahrene Diatassistentin/Diatassistenten sind fur eine konsequente und lebenslange glutenfreie Ernahrung von groser Bedeutung.

Identifying phenylalanine hydroxylase (PAH) mutations associated with sapropterin response in phenylketonuria (PKU) would be an advantageous means to determine clinical benefit to sapropterin therapy.Sapropterin response, defined as a ≥30 % reduction in phenylalanine (Phe) levels after a dose of 10 mg/kg/day sapropterin for week one and 20 mg/kg/day for week two in 112 PKU patients aged 4-45 years, was assessed in an outpatient setting. PAH was sequenced in all patients. Mutations were correlated with sapropterin response. Dietary Phe intake was increased over a 6-week period in responsive patients.Forty-six of 112 patients were sapropterin responsive. Genotypes p.[L48S];[L48S] and p.[Y414C];[Y414C] were always associated with response at a low dose. The mutation Y414C (present on 16 alleles) was most frequently associated with response. Patients with presence of the mutation L48S on at least one allele (12 alleles in 7 patients) always showed response to sapropterin. Responsive patients had a mean Phe tolerance increase of 189 % (range 11-742 %). In the 66 nonresponders, mutations R408W (38 alleles) and IVS12+1GA (18 alleles) were detected most frequently. Genotypes [IVS12+1GA];[IVS12+1GA], p.[L348V];[R408W], p.[P281L];[P281L], p.[R158Q];[R408W], and p.[R261Q];[R408W] were always associated with nonresponse.Data from the study contributes to growing evidence of the relationship between PAH genotype and PKU phenotype. In most cases, response to sapropterin therapy cannot be predicted based on the presence of a single mutation on one allele alone, although the complete PAH genotype may help to predict sapropterin responsiveness in PKU patients.

Alle therapeutischen Diatempfehlungen richten sich nach den Empfehlungen der Deutschen, Osterreichischen und Schweizerischen Gesellschaft fur Ernahrung (DACH-Empfehlungen) aus dem Jahre 2000 (Deutsche Gesellschaft fur Ernahrung et al. 2000). Bei jeder nachfolgenden Diat sollte eine Anpassung des Eiweis-, Fett-, Kohlenhydrat-, Mikronahrstoff-, Flussigkeits- und Energiebedarfs stattfinden. Besonderheiten und Ausnahmen sind den einzelnen Diatempfehlungen zu entnehmen. Dabei sind besonders der Energie-, Flussigkeits- und Mikronahrstoffbedarf um teilweise bis zu 150% der DACH-Empfehlungen anzuheben, um Mangelerscheinungen unmittelbar nach der Diagnosestellung zu beheben. Entstandene intestinale Malabsorptionen konnen so in der Regel oft nach etwa 3–4 Monaten ausgeglichen werden.

Whereas propionic acidemia (PA) is a target disease of newborn screening (NBS) in many countries, it is not in others. Data on the benefit of NBS for PA are sparse. Twenty PA patients diagnosed through NBS were compared to 35 patients diagnosed by selective metabolic screening (SMS) prompted by clinical findings, family history, or routine laboratory test results. Clinical and biochemical data of patients from 16 metabolic centers in Germany, Austria, and Switzerland were evaluated retrospectively. Additionally, assessment of the intelligent quotient (IQ) was performed. In a second step, the number of PA patients who have died within the past 20 years was estimated based on information provided by the participating metabolic centers. Patients diagnosed through NBS had neither a milder clinical course regarding the number of metabolic crises nor a better neurological outcome. Among NBS patients, 63% were already symptomatic at the time of diagnosis, and

In a group of 87 consecutive patients with hyperphenylalaninaemia born since 1990, only 3 patients showed a (temporary) decrease of serum phenylalanine levels after tetrahydrobiopterin (BH4) loading in usual doses (20 mg/kg body weight).

Die klassische Galaktosamie wird autosomal rezessiv vererbt. Die Haufigkeit betragt 1: 40.000 bis 1:60.000.Ursache ist die unzureichende Bildung des Enzyms Galaktose-1-Phosphat-Uridyltransferase (Gal-1-PUT; GALT). Der Umbau der freien Galaktose in Glukose ist dadurch gestort. Es entstehen Stoffwechselabbauprodukte, welche an verschiedenen Organsystemen Schaden verursachen, die nur zum Teil durch die derzeit empfohlene galaktosearme Diat zu beeinflussen sind.

A diet strictly low in phenylalanine from soon after birth on can protect patients with phenylketonuria against intellectual and psychomotor retardation. Our study tries to answer the questions how the patients and their relations cope with the diet, and weather they reach the serum-phenylalanine-limits recommended by the German Association of Pediatric Metabolic Diseases in 1990.

The intellectual outcome of patients with HPA (serum phe levels under free diet < 600 μmol/l) was not systematically studied so far. Therefore we tested 31 patients (age: 22 ± 4 years) for IQ (WAIS-R) and school performance. In addition cranial MRI (1.5 T unit) was obtained in 10 of these patients. The patients reached a normal IQ (X=102, SD=15; normal population: X=100, SD 15). They neither started school later than their siblings nor did they repeat classes more often, and they went to the same types of schools. The evaluation of patients' MRIs revealed no abnormalities in any case. Our results indicate that untreated patients with persistent HPA are not at risk for developing deficits in intellectual performance and white matter changes, as described for patients with treated mild or classical PKU. From this point of view a dietary treatment is not necessary in patients with HPA, as recommended most recently (1). 1. British Medical Working Party on PKU (1993). New British Recommendations for the Management of PKU. Arch Dis Child, 68: 426 - 427

Background Propionic acidemia is an inherited disorder caused by deficiency of propionyl-CoA carboxylase. Although it is one of the most frequent organic acidurias, information on the outcome of affected individuals is still limited. Study design/methods Clinical and outcome data of 55 patients with propionic acidemia from 16 European metabolic centers were evaluated retrospectively. 35 patients were diagnosed by selective metabolic screening while 20 patients were identified by newborn screening. Endocrine parameters and bone age were evaluated. In addition, IQ testing was performed and the patients’ and their families’ quality of life was assessed. Results The vast majority of patients (>85%) presented with metabolic decompensation in the neonatal period. Asymptomatic individuals were the exception. About three quarters of the study population was mentally retarded, median IQ was 55. Apart from neurologic symptoms, complications comprised hematologic abnormalities, cardiac diseases, feeding problems and impaired growth. Most patients considered their quality of life high. However, according to the parents’ point of view psychic problems were four times more common in propionic acidemia patients than in healthy controls. Conclusion Our data show that the outcome of propionic acidemia is still unfavourable, in spite of improved clinical management. Many patients develop long-term complications affecting different organ systems. Impairment of neurocognitive development is of special concern. Nevertheless, self-assessment of quality of life of the patients and their parents yielded rather positive results.