Pediat. Res. 5: 478-486 (1971) Extract A 7-year-old girl with periodic acidosis, lethargy, and coma beginning during the 1st year of life was studied. Episodes of ketoacidosis usually occurred with minor respiratory or gastrointestinal infections. There was history neither of peculiar body odor nor characteristic smell like that of sweaty feet. Hyperglycinemia, 4.2 mg/100 ml, and hyperglycinuria, 361 mg/liter, were found at times of illness with acidosis. A clinical diagnosis of ketotic hyperglycinemia was made in 1966. Glycine metabolism was therefore investigated in vivo using 14 C-labeled glycine. The oxidation of glycine to respiratory CO2 and formation of serine from glycine were found to be normal. The labeling of urinary hippurate, however, the largest component of the labeled products of glycine in the urine in normal individuals, was virtually zero. An abnormal, labeled product of glycine was found in the urine and identified as isovalerylglycine. As much as 6% of the 14 C-glycine administered was incorporated into urinary isovalerylglycine within 24 hr. Isovalerylglycine in urine was 2880 mg/24 hr, while normal individuals excrete less than 2 mg/24 hr. Isovaleric acid was found in both urine and plasma. Isovaleric acid in the plasma and urine, 2.86 mg/liter and 2.56 mg/day, respectively, was only five to six times larger than that found in normal individuals. Formation and excretion of isovalerylglycine may be a compensatory mechanism for the elimination of toxic amounts of isovaleric acid from the body. Biosynthesis of such huge amounts of isovalerylglycine may alter the overall metabolism of glycine. Isovaleric acidemia may present with hyperglycinemia and hyperglycinuria. Examination of the urine for isovalerylglycine is a convenient method for detecting the syndrome of isovaleric acidemia. SpeculationIsovaleric acidemia, in common with propionic acidemia with ketotic hyperglycinemia and methylmalonic acidemia, produces dramatic episodes of ketoacidosis. It is now clear that, like these conditions, isovaleric acidemia can also produce leukopenia and elevated concentrations of glycine in body fluids. The mechanisms causing these abnormalities are unknown. Elucidation of metabolic interfaces among these conditions could lead to understanding of the pathophysiology involved.

A 3-year-old boy presenting with convulsions and carpopedal spasm had hypomagnesemia and hypermagnesuria due to congenital magnesium-losing nephropathy. Despite chronic oral and intermittent intravenous magnesium supplementation, he remained chronically hypomagnesemic. At age 4, he developed a progressive proximal myopathy and dilated hypertrophic cardiomyopathy that ultimately contributed to his death at age 14 years. Skeletal and cardiac muscle specimens showed a mitochondrial myopathy with increased numbers of enlarged, structurally abnormal mitochondria. Muscle magnesium content was markedly decreased. Chronic oral and intermittent intravenous magnesium supplementation may be inadequate to prevent the progressive cardioskeletal myopathy associated with the chronic magnesium deficiency of congenital magnesium-losing nephropathy.

No abstract

No abstract