Argininosuccinic Aciduria

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What is argininosuccinic aciduria?

Argininosuccinic aciduria is an inherited disorder that causes ammonia to accumulate in the blood. Ammonia is toxic, especially to the nervous system, and argininosuccinic aciduria usually becomes evident in the first few days of life.

An infant with argininosuccinic aciduria may seem lethargic or be unwilling to eat, have poorly-controlled breathing rate or body temperature, experience seizures or unusual body movements, or go into a coma. Complications from argininosuccinic aciduria may include developmental delay and mental retardation. Progressive liver damage, skin lesions, and brittle hair may also be seen. Immediate treatment and lifelong management (following a strict diet and using appropriate supplements) may prevent many of these complications.

Occasionally, an individual may inherit a mild form of the disorder in which ammonia accumulates in the bloodstream only during periods of illness or other stress.

How common is argininosuccinic aciduria?

Argininosuccinic aciduria occurs in approximately 1 in 70,000 newborns.

What genes are related to argininosuccinic aciduria?

Mutations in the ASL gene cause argininosuccinic aciduria.

Argininosuccinic aciduria belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions in the cells of the liver. It processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys.

In argininosuccinic aciduria, the enzyme that starts a specific reaction within the urea cycle is damaged or missing. The urea cycle cannot proceed normally, and nitrogen accumulates in the bloodstream in the form of ammonia.

Ammonia is especially damaging to the nervous system, so argininosuccinic aciduria causes neurological problems as well as eventual damage to the liver.

How do people inherit argininosuccinic aciduria?

This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder.

Source: National Institutes of Health

Research on argininosuccinic aciduria reported by scientists at University of Padua

"We report a novel ASL pseudogene located in the centromeric region of chromosome 7, 14 novel mutations in the ASL gene, and a novel intronic polymorphism found in a cohort of Italian patients. Our approach relied exclusively on genomic DNA analysis. We found seven missense mutations, two nonsense, three small insertions/deletions, and two splicing mutations. Only two patients harbored previously described mutations, and among the novel variants only two were present in more than one kindred. The pathogenicity of the splicing mutations was demonstrated by a functional splicing assay that employed a hybrid minigene. We also performed molecular modeling using the reported three, dimensional structure of ASL to predict the functional consequences of the missense mutations. There was no genotype-phenotype correlation. Patients with neonatal onset display developmental delay and seizures despite adequate metabolic control. Moreover, hepatomegaly, fibrosis, and abnormal liver function tests are common complications in these patients, but not in patients with the late infancy form," wrote E. Trevisson and colleagues, University of Padua.

The researchers concluded: "We stress the importance of mutation analysis in patients with ASAuria, to confirm the clinical diagnosis, and to perform DNA-based prenatal diagnosis in future pregnancies of these families."

Trevisson and colleagues published their study in Human Mutation (Argininosuccinate lyase deficiency: Mutational spectrum in Italian patients and identification of a novel ASL pseudogene. Human Mutation, 2007;28(7):694-702).

For additional information, contact L. Salviati, University of Padua, Dept. of Pediatrics, Via Giustiniani 3, I-35128 Padua, Italy.

The publisher's contact information for the journal Human Mutation is: Wiley-Liss, Division John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA.

Keywords: Italy, Padua, Argininosuccinic Aciduria, Enzyme Research, Lyase, University of Padua.

This article was prepared by Proteomics Weekly editors from staff and other reports. Copyright 2007, Proteomics Weekly via NewsRx.com.