1252 NATURAL HISTORY AND DIAGNOSTIC DELAY IN PARTIAL ORNITHINE TRANSCARBAMYLASE DEFICIENCY (POTCD)

Abstract

The natural history of 13 females with POTCD was reviewed. Patients presented as early as 1 week or as late as 6 years. The most common symptoms before diagnosis were non-specific: extreme irritability (100%), recurrent vomiting and lethargy (100%), protein avoidance (92%), ataxia (75%), stage II coma (46%), failure to thrive (46%), and seizures (31%). The median delay between the onset of major symptoms (vomiting and lethargy; seizures; coma) and diagnosis was 16 mos. (range 1-142 mos.). In 38% there was a positive family history. Plasma levels at diagnosis were: NH4, 53-520 uM (NL<35); AST (median) 83 U/L; ALT (median) 337 U4/L; urea, 3-13 mg/dl; citrulline, trace-21 uM (NL: 10-34). Liver OTC activity was 2-55% of normal. Five patients had I.Q. scores < 70 at the time of diagnosis. For those with ≥ 1 episode of stage II coma, the mean I.Q. was 52. Common mis-diagnoses were gastroenteritis, colic, Reye's syndrome, psychogenic cyclical vomiting, and poor maternal-child interactions. Clues to early diagnosis are (1) a positive family history, (2) protein avoidance, (3) recurrent symptoms, (4) response to withdrawal of protein, and (5) onset at the time of weaning from breast milk. Early diagnosis allows prompt recognition and treatment of hyperammonemic episodes, thus reducing the risk of subsequent neurological impairment.