COMPASSIONATE ALLOWANCE INFORMATION

ORNITHINE TRANSCARBAMYLASE (OTC) DEFICIENCY

DESCRIPTION

Ornithine Transcarbamylase (OTC) Deficiency is a rare genetic disorder characterized by complete or partial lack of the enzyme ornithine transcarbamylase (OTC). 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. In most cases the early symptoms appear within the first three days of life and include respiratory distress, feeding difficulty, hypotonia, lethargy, and death in untreated cases. Neonatal hyperammonemic coma lasting longer than 48 hours usually results in cortical atrophy and intellectual disability. 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.

ALTERNATE NAMES

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

DIAGNOSTIC TESTING AND CODING

• Laboratory confirmation of the gene defect is necessary. The definitive diagnostic test for OTC requires the determination of enzyme activity from a liver biopsy. 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.

• The presence of hyperammonemia, elevated urinary orotic acid and a very low BUN level may present diagnostic clues. In addition, blood ammonia studies, serum amino acid quantitation may show elevated ornithine, glutamine, and alanine levels and relatively low citrulline levels, but these changes are neither invariable nor diagnostic. Urine organic acid and amino acid analysis are helpful in ruling out other conditions.

• Beyond demonstration of hyperammonemia, the only basis for clinical diagnosis is demonstration of elevated urinary orotic acid.

• 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.

TREATMENT

• 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.

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

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

PROGRESSION

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

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation: Clinical evaluation should include a description of physical and developmental findings, and current pediatric and neurological examination. Routine Laboratory tests will help rule out other disorders and MRI findings may be characteristic of ALX.

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets Listing

110.08
111.02
111.17
112.02
112.05

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

Medical Equals

* Adjudicators may, at their discretion, use the Medical Evidence of Record or Listings suggested to evaluate the claim. However, the decision to allow or deny the claim rests with the adjudicator.