Branched-chain Amino Acids in Two Mentally Retarded Sibs

There is increasing interest in the importance of pyridoxine in brain disorders of childhood. Convulsions have occurred in infants receiving a pyridoxine (vitamin B6) deficient diet (Coursin, 1955), and Bessey, Adam, and Hansen (1957) have shown that some infants have a greater requirement than others for this vitamin. In the deficiency state, small amounts of vitamin B6 stop the convulsions, but greater than normal amounts are required to correct the increased xanthurenic acid excretion (Bessey et al., 1957). In the dependency states (Scriver, 1960) described in sibs (Waldinger and Berg, 1963), increased excretion of xanthurenic acid has not been a feature, though high doses of vitamin B6 are required to control convulsions. In 1963, O'Brien and Jensen considered whether vitamin B6 dependency could be a causal factor in mentally retarded persons who did not have convulsions, and during the screening of a mental institution they found two women (aged 17 and 31 years) with evidence of vitamin B6 dependency. These authors suggested that the ratio of the concentrations of 3-hydroxykynurenine and 3-hydroxyanthranilic acid found in urine would be superior to the measurement of the excretion of xanthurenic acid as an indicator of vitamin B6 dependency. The value of this index has been described by Heeley (1965), whose values for the index in normal children agree with those of Michael, Drummond, Doeden, Anderson, and Good (1964). Biochemical screening of mentally retarded children at The Hospital for Sick Children revealed two sibs who metabolized a tryptophan load abnormally at the pyridoxine-dependent kynureninase reaction. In addition, both sibs had raised levels of leucine in their sera.