ABSTRACT
The disorder was first described by Shih, Efron and Moser [1] in a patient with mental retardation, irritability and myoclonic spasms who had intermittent attacks of hyperammonemia and ataxia. He was described by the parents as having attacks
in infancy of sudden jumping, as though he had been stuck by a pin. Dropping of the head was a concomitant of these myoclonic spells. A small number of patients has since been reported, six from a single consanguineous kindred [2-4]. The fundamental defect is an inability to transport ornithine into mitochondria [5-8] (Figure 34.1). The gene was cloned
Cytosol
Urea cycleArginine
Urea
COOH
H2NCH
(CH2)2
CH2NH2
COOH
H2NCH
(CH2)2
CH2NH2 Ornithine
Ornithine Ornithine decarboxylase
Putrescine
Citric acid cycle
2-Oxoglutaric acid
Glutamic acid ProlineProline
Lysine
Glutamic semialdehyde
Carbamyl phosphate
Lysine
Homocitrulline Homocitrulline
Carbamyl phosphate Orotic acidMitochondrion
NH4 Citrulline
-Pyrroline Carboxylic
acid
by Camacho and colleagues [9] and localized to chromosome 13q14. Three mutations were found to account for 21 of 22 possible mutant alleles including F188 which is common in French-Canadian patients. An additional mutation has been found in two families of Mexican descent with a mild phenotype [10].
