Method: DNAwas extracted from urine and two blood specimens from the proband as well as maternal blood. The coding region and the intron-exon boundaries of the OTC gene (NM_000531.5) were sequenced. Results: The proband had a normal (46XY) karyotype excluding Klinefelters' syndrome. Sequence analysis in 3 samples consistently revealed two mutations at the same nucleotide in the proband: c.542A>T (p.Glu181Val) and c.542A>G (p.Glu181Gly); the former being 2-3 times more prevalent with neither being in the mother. Discussion: Mutations at residue 181 are consistent with OTC deficiency. p.Glu181Gly has been reported in a neonate. p.Glu181Val is novel and is predicted by PolyPhen-2 to be benign though SIFT predicts it to affect protein function with low confidence. Possible causes include de-novo mutation in mother followed by somatic mutation in the fetus, or initial somatic mutation in the fetus and a subsequent second mutation. Ornitine transcarbamylase deficiency (OTCD) is the most frequent urea cycle error and results from mutations in the OTC gene-that encodes a 354-residue polypeptide. The clinical picture in females is highly variable even within a family, depending on the X-inactivation pattern in liver. Mutations that lead to late-onset presentations may lead to life-threatening disease and may be unrecognized. We present a 14 months-old girl who manifested with recurrent stroke episodes after a respiratory infection that triggered a hyperammonemic crisis; investigations revealed hyperammonemia (384 μmol/L), coagulopathy, elevated liver enzymes, lactic acidosis and massive orotic aciduria (orotate/ creatinine ratio 5000 mmol/mol creatinine, reference range <11), being highly suggestive of ornithine transcarbamylase deficiency. DNA analysis revealed a novel mutation in the 6th exon of the OTC gene [c.628A>T (p.Lys210X)], leading to a premature stop of translation. Searching for OTCD mutations is laborious and expensive; if all OTCD causing mutations were known, mutation screening might be simpler. OTCD should be considered in the differential diagnosis of unexplained acute neurological presentation, even without a suggestive family history. This report expands the clinical, biochemical and molecular spectrum of OTCD with a female case heterozygous for the novel c.628A>T OTC mutation. Background: Hyperammonemia is well known in the cat family on an arginine deficient diet. Several studies have been conducted to explain this phenomenon. Morris and Rogers described arginine as an essential amino acid for the cat family and Jones found that cats are unable to produce ornithine. Levillain found that hyperammonemia in cats can be prevented and treated with either arginine or citrulline supplementation but not with ornithine. One cheetah breeding population, on a well balanced diet, in South Africa experienced chronic problems with hyperammonemia. The urinary creatinine excretion in the cat family is extremely high. Since creatine is synthesized from arginine, the high creatinine values indicated an enormous flux through arginine. Therefore arginine cannot be essential and the low arginine and citrulline concentrations indicated the presence of a possible catabolic pathway for at least one of the intermediates of the urea cycle.