Hyperammonemia Type II; Hyperammonemia due to Ornithine Transcarbamylase Deficiency; Ornithine Carbamyltransferase Deficiency

Ornithine Transcarbamylase (OTC) Deficiency is a rare genetic disorder characterized by complete or partial lack of the enzyme ornithine transcarbamylase. OTC is one of six enzymes that play a role in the break down and removal of nitrogen from the body, a process known as the urea cycle. Accumulation of ammonium in the brain and blood usually follows a protein load or intermittent infection. OTC deficient patients are particularly sensitive to toxic effects of valproate.

Diagnostic testing: Laboratory confirmation of the gene defect is necessary.

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  Liver biopsy;

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  The combination of family history of the disorder, clinical presentation, plasma amino acid and urine orotic acid testing, and in some cases, molecular genetic testing are often sufficient for diagnostic confirmation, eliminating the risks of liver biopsy;

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  Presence of hyperammonemia;

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  Elavated urninary orotic acid;

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  Very low blood urea nitrogen (BUN) levels;

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  Blood ammonia studies;

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  Serum amino acid quantitation showing elevated ornithine, glutamine, and alanine levels and relatively low citrulline levels; and

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  Urine organic acid and amino acid analysis are helpful in ruling out other conditions.

Enzymatic deficiency of the ornithine transcarbamylase enzyme can be further confirmed with molecular diagnosis. However, even using a combination of different molecular analytic strategies, only 80% of proven enzymatic deficiencies can be shown to have genetic mutation.

Physical findings: In most cases the early symptoms appear within the first three days of life and include:

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  Respiratory distress;

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  Feeding difficulty;

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  Hypotonia (weak muscle tone);

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  Lethargy (lack of energy and enthusiasm);

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  Neonatal hyperammonemic coma lasting longer than 48 hours usually results in cortical atrophy and intellectual disability; and

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  Death in untreated cases.

ICD-9: 270.6

Morbidity and mortality are high, especially in individuals with the neonatal form.

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  Diet changes to discontinue protein intake is mandatory, with compensatory increases in carbohydrates and lipids in order to offset any catabolic tendency to draw on muscle amino acids for energy. Vegetarian diets are preferred because dietary protein intake often is associated with migraine-like headache.

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  Hemodialysis is used to achieve rapid reduction of extremely high blood ammonia levels (in some cases exceeding 2000 mg/dL) in comatose individuals.

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  Intravenous administration of sodium benzoate, arginine, and sodium phenylacetate in a large medical facility setting with close laboratory monitoring is a treatment form.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

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  Clinical evaluation should include a description of physical and developmental findings, and current pediatric and neurological examination; and

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  Routine Laboratory tests will help rule out other disorders and MRI findings may be characteristic of ALX.

Suggested Listings for Evaluation:

REMARKS

Laboratory and clinical findings consistent with OTC deficiency and progressive encephalopathy with or without treatment.

Laboratory and clinical findings consistent with OTC deficiency and progressive encephalopathy with or without treatment.

Laboratory and clinical findings consistent with OTC deficiency and progressive encephalopathy with or without treatment.

Laboratory and clinical findings consistent with OTC deficiency and progressive encephalopathy with or without treatment.

Laboratory and clinical findings consistent with OTC deficiency and progressive encephalopathy with or without treatment.