NeurometPlus

Incidence

X-linked dominant. Heterozygous females are either asymptomatic or express orotic aciduria spontaneously or after protein intake. This identifies carriers.

Clinical Characteristics

Heterozygous females are either asymptomatic or express orotic aciduria spontaneously or after protein intake. This identifies carriers. Females may also be affected by symptoms with various degrees of intensity, ranging from dislike for proteins to chronic vomiting, growth retardation, hypotonia, psychomotor retardation, hyperammonemic coma, or psychiatric disorders. Rowe et al. (1986) reviewed 13 symptomatic female heterozygotes. They presented as early as the first week of life or as late as the sixth year. Symptoms before diagnosis were nonspecific: episodic extreme irritability (100%), episodic vomiting and lethargy (100%), protein avoidance (92%), ataxia (77%), stage II coma (46%), delayed growth (38%), developmental delay (38%), and seizures (23%). Onset at the time of weaning from breast milk was frequent. Including the proband, 42% of females in the 13 families had symptoms. Gilchrist and Coleman (1987) reported 2 heterozygous females who had late onset of severe symptoms. Encephalopathy and focal neurologic deficits began at age 36 years in 1 and at age 38 years in the other. The second had increased urine orotate after a protein meal and had had a lifelong aversion to eating meat, which usually precipitated headaches. Arn et al. (1989) discussed phenotypic effects of heterozygosity for mutations at the OTC locus. Arn et al. (1990) reported that otherwise normal women who are carriers of a mutant OTC allele are at increased risk for hyperammonemic coma, especially during puerperium. They recommended that any woman who presents with an episode of progressive lethargy and stupor, evidence of acute cortical dysfunction, or coma, especially during pregnancy, be examined for OTC deficiency by pedigree analysis, a search for a history of previous episodes, and the measurement of plasma ammonium and, if immediately available, plasma glutamine levels. The early identification of hyperammonemia provides an opportunity to correct plasma ammonium levels by intravenous therapy with sodium benzoate, sodium phenylacetate, and arginine hydrochloride. Lee et al. (2002) reported a female infant with skin lesions resembling acrodermatitis enteropathica who was subsequently found to have OTC deficiency. Infectious causes and zinc deficiency were ruled out, and resolution of the eruption occurred after arginine and citrulline supplementation was instituted.

Precipitants

Protein intake. Puerperium period often trigger an attack in heteroz females.

Provocation Tests

Protein intake trigger elevation of ammonia levels.

Diagnostic Procedures

Ammonia levels elevated, also orotic acid in urine, glutamine elevated in serum.