The nutritional management of urea cycle disorders

Institute of Child Health and Great Ormond Street Hospital for Children, London, United Kingdom.
Journal of Pediatrics (Impact Factor: 3.79). 02/2001; 138(1 Suppl):S40-4;discussion S44-5. DOI: 10.1067/mpd.2001.111835
Source: PubMed


Diet is one of the mainstays of the treatment of patients with urea cycle disorders. The protein intake should be adjusted to take account of the inborn error and its severity and the patient's age, growth rate, and individual preferences. Currently, the widely used standards for protein intake are probably more generous than necessary, particularly for those with the more severe variants. Most patients, except those with arginase deficiency, will need supplements of arginine, but the value of other supplements including citrate and carnitine is unclear. Any patient on a low-protein diet should be monitored clinically and with appropriate laboratory tests. All should have an emergency (crisis) regimen to prevent decompensation during periods of metabolic stress.

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    • "Leonard J. 2001 [9] UCD USA/UK FAO/WHO/UNU (1985) safe intakes likely excessive. Revised safe values [2] adopted. "
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    ABSTRACT: Dietary restrictions required to manage individuals with Inborn Errors of Metabolism (IEM) are essential for metabolic control, however may result in an increased risk to both short and long- term nutritional status. Dietary factors most likely to influence nutritional status include energy intake, protein quality and quantity, micronutrient intake and the frequency and extent to which the diet must be altered during periods of increased physical or metabolic stress. Patients on the most restrictive diets, including those with intakes consisting of low levels of natural protein or those with recurrent illness or frequent metabolic decompensation carry the most nutritional risk. Due to the difficulties in determining condition specific requirements, dietary intake recommendations and nutritional monitoring tools used in patients with IEM are the same as, or extrapolated from, those used in healthy populations. As a consequence, evidence is lacking for the safest dietary prescriptions required to manage these patients long term, as tolerance to dietary therapy is generally described in terms of metabolic stability rather than long term nutritional and health outcomes. As the most frequent therapeutic dietary manipulation in IEM is alteration in dietary protein, and as protein status is critically dependent on adequate energy provision, the use of a Protein to Energy ratio (P:E ratio) as an additional tool will better define the relationship between these critical components. This could accurately define dietary quality and ensure that not only an adequate, but also a safe and balanced intake is provided.
    Molecular Genetics and Metabolism 08/2014; 112(4). DOI:10.1016/j.ymgme.2014.05.008 · 2.63 Impact Factor
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    • "One of the key components of the urea cycle is arginine, an amino acid with several anabolic functions. As part of the urea cycle it is a potent stimulator of urea production, and as such it is often administered to patients with inborn errors of the urea cycle to reduce the hyperammonaemia that is symptomatic to the disorder (Leonard, 2001). It may therefore also be useful as a treatment for urea cycle impairment in IUGR. "
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    ABSTRACT: Urea production may be impaired in intrauterine growth restriction (IUGR), increasing the risk of toxic hyperammonaemia after birth. Arginine supplementation stimulates urea production, but its effects in IUGR are unknown. We aimed to determine the effects of IUGR and arginine supplementation on urea production and arginine metabolism in the ovine foetus. Pregnant ewes and their foetuses were catheterised at 110 days of gestation and randomly assigned to control or IUGR groups. IUGR was induced by placental embolisation. At days 120 and 126 of gestation, foetal urea production was determined from [14C]-urea kinetics and arginine metabolism was determined from the appearance of radioactive metabolites from [3H]-arginine, both at baseline and in response to arginine or an isonitrogenous mixed amino acid supplementation. Urea production decreased with gestational age in the embolised animals (13.9 ± 3.1 to 11.2 ± 3.0 μmol/kg per min, P ≤ 0.05) but not in the controls (13.3 ± 3.5 to 14.8 ± 6.0 μmol/kg per min). Arginine supplementation increased urea production in both groups, but only at 126 days of gestation (control: 15.0 ± 8.5 to 17.0 ± 9.4 μmol/kg per min; embolised: 11.7 ± 3.1 to 14.3 ± 3.1 μmol/kg per min, P ≤ 0.05). Embolisation reduced foetal arginine concentrations by 20% ( P ≤ 0.05) while foetal arginine consumption was reduced by 27% ( P ≤ 0.05). The proportions of plasma citrulline and hydroxyproline derived from arginine were reduced in the embolised animals. These data suggest that foetal urea production and arginine metabolism are perturbed in late gestation after placental embolisation.
    animal 06/2007; 1(5):699-707. DOI:10.1017/S1751731107710273 · 1.84 Impact Factor
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    • "These symptoms are usually precipitated by protein intake beyond what the patient can metabolize or catabolism of lean body mass resulting from intercurrent infection, trauma, inadequate energy intake, or inadequate protein or EAA intake. Nutrition management of patients with a defect of an enzyme in the urea cycle includes: (1) administration of suYcient energy to support anabolism, (2) restriction of protein intake to that tolerated by the patient without producing excess NH 3 , (3) provision of EAAs in adequate amounts to support growth, (4) supplements of " conditionally " essential ARG or L-CIT in all except arginase deWciency , and (5) provision of all required minerals and vitamins in adequate amounts for age [6] [7]. A number of reports have documented poor physical growth of patients on restricted protein intakes [8] [9] [10] [11] [12]. "
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    ABSTRACT: Poor growth has been described in patients with urea cycle enzyme defects treated with protein-restricted diets, while protein status is seldom reported. To assess the effects of nutritional therapy with a medical food on growth and protein status of patients with a urea cycle enzyme defect. A 6-mo multicenter outpatient study was conducted with infants and toddlers managed by nutrition therapy with Cyclinex-1 Amino Acid-Modified Medical Food with Iron (Ross Products Division, Abbott Laboratories, Columbus, OH). Main outcome variables were anthropometrics and plasma amino acids (selected), albumin, and transthyretin concentrations. Seventeen patients completed the study. Mean (+/-SE) baseline age was 11.30+/-3.20 months (median 4.40 months; range 0.22-38.84 months). Length and weight z-scores increased significantly during the 6-month study. Head circumference increased, but not significantly. Three patients were stunted and two were wasted (-2.0 z-score) at baseline while at study end, only one patient was both stunted and wasted. The majority of patients increased in length, head circumference, and weight z-scores during study. Mean (+/-SE) plasma albumin concentration increased from 34+/-2g/L at baseline to 38+/-1g/L at study end. Plasma transthyretin increased from a mean (+/-SE) of 177+/-13 mg/L at baseline to 231+/-15 mg/L at study end. No correlation was found between plasma NH(3) concentrations and medical food intake. Plasma NH(3) concentration was positively correlated with the percentage of Food and Agriculture Organization/World Health Organization/United Nations recommended protein ingested. Intakes of adequate protein and energy for age result in anabolism and linear growth without increasing plasma NH(3) concentrations. Medical food intakes did not correlate with plasma NH(3) concentrations.
    Molecular Genetics and Metabolism 01/2006; 86(4):448-55. DOI:10.1016/j.ymgme.2005.08.012 · 2.63 Impact Factor
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