ARG1
Arginase is one of five enzymes which play a role in the breakdown of nitrogen and its removal from the body and is encoded for by the ARG1 gene 1.
The breakdown and removal of nitrogen from the body forms part of the urea cycle. Ammonia is formed in the body when proteins are broken down, if not removed this ammonia can quickly reach harmful levels in the blood with the nervous system being especially sensitive to excess levels of ammonia 1. Arginase is the final enzyme in the urea cycle, producing urea which is excreted from the body in urine, and ornithine which can be used to generate new DNA products and so is vital for healthy tissue function and development 2. Deficiency in arginase activity is termed argininemia.
There are several SNPs in ARG1 associated with a very severe health impact through a total loss of arginase activity. However, the SNP rs28941474, or T32C, which can be severe in those carrying two risk alleles, may also induce milder poor health outcomes when a single risk allele is present.
| rsID Number | Major Allele | Minor Allele | Minor Allele Frequency (%) | Major Amino Acid | Minor Amino Acid |
|---|---|---|---|---|---|
| rs28941474 | t | c | 0.0008 | Ile | Thr |
Risk Description
The very rare risk ‘C’ allele of T32C in the ARG1 gene is associated with pronounced arginase deficiency when two risk alleles are present 3,4. Severe symptoms include frequent seizures, poor childhood growth and intellectual disability which manifest a few months after birth. As such the mutation is rapidly detected and sufferers can benefit from a reduced nitrogen diet.
There is some evidence to suggest that in those carrying a single risk ‘C’ allele total arginase activity may also be reduced, although no direct evidence of symptoms arising from this reduction is provided.
Direct Nutrients:*
| Ingredient | Active Ingredient | Effect |
|---|---|---|
| Manganese |
Manganese is a vital mineral cofactor required by ARG1 to function correctly 5. It is unclear what risk is associated with carrying a single ‘C’ allele in T32C however manganese supplementation may ensure that ARG1 functions maximally. |
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Lifestyle Considerations:
| Behavior | Description |
|---|---|
| Reduced nitrogen (protein) diet |
Restriction of dietary nitrogen has been successful in treating severe forms of arginase deficiency, as can occur when carrying two risk ‘C’ alleles of T32C, preventing a buildup of ammonia 3. It is unclear exactly to what extent carrying a single risk ‘C’ allele of T32C affects nitrogen processing and ammonia accumulation. Blood tests are available to assess levels of ammonia in the blood, if elevated a reduction in dietary protein may prove beneficial. |
Discuss this information with your doctor before taking any course of action.