A Rare Cause of Spasticity and Microcephaly: Argininemia

Argininemia is an autosomal recessive urea cycle disorder caused by the deficiency of arginase. Our first case presented with psychomotor retardation, difficulty of walking, and progressive tiptoeing. Laboratory investigations revealed mildly elevated hepatic enzymes and elevated plasma arginine concentration. Molecular genetic analysis was performed for suspected argininemia and a novel homozygous mutation c. 231C> A (p. S77R) was detected in the ARG1 gene. The second patient was admitted because of poor head control when he was aged 6 months. Microcephaly was detected in his physical examination, and basic metabolic tests were studied. Elevated levels of plasma arginine and orotic acid in urine organic acid analysis were compatible with argininemia. A homozygous mutation c.703G> C (p. G235R) was detected in the ARG1 gene and the diagnosis was confirmed. Arginineemia is a rare cause of progressive spastic diplegia. Patients may be mistakenly diagnosed as having cerebral palsy. Microcephaly may be the initial clinical finding of the disorder.