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The ketogenic diet is well tolerated and can be effective in patients with argininosuccinate lyase deficiency and refractory epilepsy.

ABSTRACT: Argininosuccinate lyase (ASL) deficiency (MIM 608310, McKusick 207900) is a rare disorder of the urea cycle, which leads to a deficiency of arginine and hyperammonemia. Epilepsy is a frequent complication of this disorder. A ketogenic diet (KD) can be a very effective therapy for refractory epilepsy, and it has been widely used in children. Until now, no experiences with the KD in patients with urea cycle defects have been reported.We present two cases of patients with ASL deficiency and refractory epilepsy who were treated with a KD. In both patients, the KD was initiated during a hospital admission and the fat percentage of the diet was increased to above 90% in five equal steps. In patient 1, during the KD the protein intake was continued as before, and in patient 2 the natural protein was increased with 0,2 g/kg/day while the protein from the amino acid supplement (UCD-2(®), Milupa) was decreased with 0,3 g/kg/day. During and after the introduction of the KD, all biochemical parameters reflecting urea cycle function and ammonia levels were stable in both patients and no signs of derangement were detected. On the KD, patient 1 demonstrated a reduction in seizure frequency of >50%, and an increase in well-being. In patient 2, no effects of the KD on the seizure frequency were noted and after 6 months the KD was discontinued.Concluding, the KD does not cause metabolic derangement, is well tolerated, and can be effective in patients with ASL deficiency who are treated with a protein restriction.

SUBMITTER: Peuscher R

PROVIDER: S-EPMC3509918 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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The ketogenic diet is well tolerated and can be effective in patients with argininosuccinate lyase deficiency and refractory epilepsy.

Peuscher Rosanne R Dijsselhof Monique E ME Abeling Nico G NG Van Rijn Margreet M Van Spronsen Francjan J FJ Bosch Annet M AM

JIMD reports 20111225

Argininosuccinate lyase (ASL) deficiency (MIM 608310, McKusick 207900) is a rare disorder of the urea cycle, which leads to a deficiency of arginine and hyperammonemia. Epilepsy is a frequent complication of this disorder. A ketogenic diet (KD) can be a very effective therapy for refractory epilepsy, and it has been widely used in children. Until now, no experiences with the KD in patients with urea cycle defects have been reported.We present two cases of patients with ASL deficiency and refract ...[more]

PMID: 23430928

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Project description:The urea cycle consists of six consecutive enzymatic reactions that convert waste nitrogen into urea. Deficiencies of any of these enzymes of the cycle result in urea cycle disorders (UCD), a group of inborn errors of hepatic metabolism that often result in life threatening hyperammonemia. Argininosuccinate lyase (ASL) is a cytosolic enzyme which catalyzes the fourth reaction in the cycle and the first degradative step, that is, the breakdown of argininosuccinic acid to arginine and fumarate. Deficiency of ASL results in an accumulation of argininosuccinic acid in tissues, and excretion of argininosuccinic acid in urine leading to the condition argininosuccinic aciduria (ASA). ASA is an autosomal recessive disorder and is the second most common UCD. In addition to the accumulation of argininosuccinic acid, ASL deficiency results in decreased synthesis of arginine, a feature common to all UCDs except argininemia. Arginine is not only the precursor for the synthesis of urea and ornithine as part of the urea cycle but it is also the substrate for the synthesis of nitric oxide, polyamines, proline, glutamate, creatine, and agmatine. Hence, while ASL is the only enzyme in the body able to generate arginine, at least four enzymes use arginine as substrate: arginine decarboxylase, arginase, nitric oxide synthetase (NOS) and arginine/glycine aminotransferase. In the liver, the main function of ASL is ureagenesis, and hence, there is no net synthesis of arginine. In contrast, in most other tissues, its role is to generate arginine that is designated for the specific cell's needs. While patients with ASA share the acute clinical phenotype of hyperammonemia, encephalopathy, and respiratory alkalosis common to other UCD, they also present with unique chronic complications most probably caused by a combination of tissue specific deficiency of arginine and/or elevation of argininosuccinic acid. This review article summarizes the clinical characterization, biochemical, enzymatic, and molecular features of this disorder. Current treatment, prenatal diagnosis, diagnosis through the newborn screening as well as hypothesis driven future treatment modalities are discussed.

Dataset Information

The ketogenic diet is well tolerated and can be effective in patients with argininosuccinate lyase deficiency and refractory epilepsy.

Publications

The ketogenic diet is well tolerated and can be effective in patients with argininosuccinate lyase deficiency and refractory epilepsy.

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