Keiya Tada

Hyperalaninemia, hyperpyruvicemia and lactic acidosis due to pyruvate carboxylase deficiency of the liver; Treatment with thiamine and lipoic acid

A 16-month-old female infant with severe mental and motor retardation, clinically diagnosed as Leighs encephalomyelopathy, forms the basis of this study. This infant was found to have lactic acidosis, low cerebrospinal fluid glucose, hyperalaninemia, and increased levels of urine lactate, pyruvate and alanine. These laboratory studies suggested an inborn error in gluconeogenesis. Further investigation revealed a low level of hepatic pyruvate carboxylase activity. The patients elder sister who also had mental and motor deterioration was then also found to have an elevated blood lactate. These two siblings clinically and biochemically showed improvement with treatment consisting of thiamine and lipoic acid.

α-l-Iduronidase activity in leukocytes: Diagnosis of homozygotes and heterozygotes of the Hurler syndrome

The activity of α-l-iduronidase was determined in leukocytes from two patients with the Hurler syndrome, five obligatory heterozygotes, one patient with the Hunter syndrome, and ten normal individuals. It was found that the determination of α-l-iduronidase in leukocytes was a useful method for differential diagnosis between the Hurler and Hunter syndromes. Heterozygotes of the Hurler syndrome showed approximately 50% level of α-l-iduronidase activity in leukocytes as compared with that of normal individuals.This suggests that the determination of α-l-iduronidase activity may be available for the carrier detection of the Hurler syndrome.

Treatment of Phenylketonuria during Early Infancy

Four children with phenylketonuria (PKU) in whom dietary therapy was started prior to 3 months of age are described. In 3 of these patients, phenylalanine deficiency syndromes, such as listlessness, poor gain in weight diarrhea, vomiting anemia and hypoproteinemia, develoved when their serum levels of phenylalanine dropped below a normal range due to excessive restriction of phenylalanine intake, only for few weeks. There is a possibility that protein malnutrition in early infancy may produce a dangerous effect on the developing brain. In order to prevent protein malnutrition, serum phenylalanine levels should be maintained higher than a normal level in the early treatment of PKU, because the need for phenylalanine per kilogram of body weight is greater during early infancy and degradative pathway to phenylpyruvate is sill premature. Our experience suggested that : 1) Initial intake of phenylalanine should be 50 mg per kilogram per day or more in the early infancy. It is appropriate to keep the serum level of phenylalanine at about 8 mg/100 ml (between 5-10 mg/100 ml) during the dietary treatment.