The Genetics of Argininemia
by James Washington
Arginase is the final enzyme in the urea cycle it is responsible for hydrolyzing arginine to urea and ornithine. Low levels of arginase cause an accumulation of arginine and ammonia. The buildup of ammonia poisons the central nervous system and causes mental retardation. Due to a genetic defect, the body can be deficient in arginase and the resulting disorder is known as argininemia. Argininemia can affect both males and females. Even though one is born with the disease its affects often go unnoticed until the child reaches an age of two or three.
Argininemia is a genetic disease because the deficiency in arginase is caused by mutations in DNA. These mutations are inherited from both the mother and the father of the child, and cause the child to synthesize invalid arginase. Analyzing the causes of Argininemia is done by amplifying DNA samples from affected individuals, and their parents by means of the polymerase chain reaction. The resultant DNA can then be cloned and sequenced. The results of DNA sequencing of one patient showed that there were mutations on two different alleles (Uchino, 1992). One allele was inherited from the patients mother, this allele had a mutation at base 365 where a guanine had been changed to an adenine. The other allele was inherited from the father and had a mutation at base 703 where a guanine was changed to a cytosine. This patient was a compound heterozygote which means that argininemia is heterogeneous.
In a different individual with argininemia the mutations were more severe. On one allele a four base deletion in exon three caused a frame shift at amino acid residue 87 and made a new stop codon at residue 132 (Haraguchi, 1990). On the other allele a base deletion occurred in exon 2 causing a stop codon at amino acid residue 31. The allele with the four base deletion was inherited from the patients father, and the other from the mother.
There have been cases in which the condition of argininemia was improved by different treatment techniques. However, because it is a genetic disease there is no cure for argininemia today. Different drugs that convert nitrogen to an excretable form can be administered. A high calorie low protein diet with amino acid supplements is often used as a treatment for argininemia. This type of controlled diet seems to be more helpful to patients whose DNA mutations are of a lesser severity such as a single base change rather than a deletion (Uchino, 1995). Blood transfusion has been used to treat argininemia. One patient under went a red blood cell replacement, by means of a blood cell separator (Sakiyama, 1984). The affected blood cells were exchanged for normal blood cells from a donor. This patient was then able to excrete the toxins that once poisoned his body, as a result he showed a significant improvement in cognitive and motor skills.

Haraguchi, Y. "Molecular Basis of Argininemia. Identification of Two Discrete FrameShift Deletions in the LiverType Arginase Gene." 86 (1990): 34750.

Sakiyama, T. "A Successful Trial of Enzyme Replacement Therapy in a case of Argininemia." 142 (1984): 23948.

Uchino, T. "Molecular Basis of Phenotypic Variation in Patients with Argininemia." 96 (1995): 25560.

Uchino, T. "Three Novel Mutations in the LiverType Arginase Gene in Three Unrelated Japanese Patients with Argininemia." 51 (1992): 140612.

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