Dietary management of urea cycle disorders: European practice.

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 0-16y and 30% (n=137) >16y. 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.

Benzoate treatment and the glycine index in nonketotic hyperglycinaemia.

High-dose benzoate treatment aimed at reducing plasma glycine levels to normal reduces seizures and increases wakefulness in patients with nonketotic hyperglycinaemia (NKH). Since benzoate metabolism is dependent on the available glycine pool, and since the glycine pool is variably affected by the deficiency in the glycine cleavage enzyme system, we examined the importance of interpatient variability in benzoate requirement. To correct for the dietary glycine contribution, the glycine index was introduced as the molar requirement of benzoate dose necessary to normalize plasma glycine levels and subtracting from that the dietary glycine intake, both corrected for weight. The glycine index varied between 3.62 and 4.87 mmol/kg per day in five patients with a poor neurodevelopmental outcome and between 0.92 and 1.90 mmol/kg per day in four patients with a better neurodevelopmental outcome, and was 2.54 mmol/kg per day in a single patient with an intermediate outcome. The glycine index was stable over time within each patient. Exceeding the balance by either increasing food glycine intake or decreasing the benzoate dose resulted in increased glycine levels. Exceeding the glycine tolerance by increasing benzoate resulted in elevated and toxic levels of benzoate. The glycine index is a stable, individually specific parameter in patients with NKH. It has clinical consequences for the dose of benzoate required and the role of dietary management. Through its correlation with neurodevelopmental outcome, the glycine index points to potential genetic factors that could contribute to the psychomotor retardation in NKH.