NeurometPlus

Incidence

Autosomal recessive. Very rare condition.

Clinical Characteristics

Tada et al. (1967) reported this disorder in a brother and sister with mental retardation. The parents were first cousins. The patients excreted excessive amounts of xanthurenic acid, kynurenic acid, 3-hydroxykynurenine, and kynurenine after tryptophan loading. This disturbance was temporarily corrected by large doses of vitamin B6. The activity of kynureninase in the liver was markedly reduced. The activity was appreciably restored by the addition of pyridoxal phosphate. This disorder is due to a defect in kynureninase, a vitamin B6-dependent enzyme in the tryptophane catabolic pathway. Both B6-responsive and B6-unresponsive forms are known. In 6 of 9 children born of first-cousin Algerian parents, Cheminal et al. (1996) found muscular hypertonia, psychomotor retardation, stereotyped gestures, congenital deafness, and nonprogressive encephalopathy. Each of the affected children had episodes of sudden worsening of their neurologic status. These episodes occurred spontaneously or during viral illnesses. At the age of 37 months, one female child had an episode of tachycardia, irregular breathing, and arterial hypotension, leading to coma and death. Two children developed renal tubular dysfunction and renal or metabolic acidosis. The only biochemical abnormality noted in these children was a massive hyperkynureninuria, seen only during periods of coma or after intravenous protein loading.

Precipitants

Neurologic status worsened by viral illness. A massive hyperkynureninuria is seen only during periods of coma or after intravenous protein loading.

Provocation Tests

Patients excreted excessive amounts of xanthurenic acid, kynurenic acid, 3-hydroxykynurenine, and kynurenine after tryptophan loading. A massive hyperkynureninuria is seen only during periods of coma or after intravenous protein loading.

Diagnostic Procedures

Kynureninase deficiency in the liver. Kynureninuria. 3-hydroxykynureninuria. Xanthurenic aciduria.