Subject(s)
Hyperoxaluria, Primary/complications , Kidney Calculi/etiology , Urinary Bladder Calculi/etiology , Adolescent , Adult , Alcohol Oxidoreductases/deficiency , Carbohydrate Dehydrogenases/deficiency , Child , Child, Preschool , Female , Humans , Hyperoxaluria, Primary/classification , Hyperoxaluria, Primary/enzymology , Infant , MaleABSTRACT
We describe 14 patients with glutaric aciduria type 1 in five Canadian Indian kindreds living in Manitoba and northwest Ontario. The patients had marked clinical variability of the disease, even within families. Eight followed the typical clinical course of normal early growth and development until the onset of neurologic abnormalities, often precipitated by infection, between 6 weeks and 7 1/2 months of age. Five patients had early developmental delay; one was thought to be normal until 8 years of age. Three patients died, seven are severely mentally and physically handicapped, and four have only mild mental retardation or incoordination. Six patients had macrocephaly in the neonatal period. Computed tomography was done for 12 patients, and findings were abnormal in 11. Glutaric acid and 3-hydroxyglutaric acid were detected in increased amounts in the urine of all patients, but the concentrations were much lower than those in most other reported patients. Glutaryl coenzyme A dehydrogenase activity in skin fibroblasts, interleukin-2-dependent lymphocytes, or both, ranged from 0% to 13% of control values. There was no correlation between clinical severity and urine glutaric acid concentration or level of residual enzyme activity. We recommend that organic acid analysis of the urine be done in patients with unexplained cerebral palsy-like disorders, especially if the computed tomographic scan is abnormal. If there is suspicion of glutaric aciduria, glutaryl-coenzyme A dehydrogenase should be measured in fibroblasts or lymphocytes even if glutaric acid is not increased in the urine.
Subject(s)
Amino Acid Metabolism, Inborn Errors/genetics , Glutarates/metabolism , Indians, North American/genetics , Oxidoreductases Acting on CH-CH Group Donors , Oxidoreductases/deficiency , Adult , Canada , Child , Child, Preschool , Female , Glutaryl-CoA Dehydrogenase , Humans , Infant , Male , PhenotypeABSTRACT
This report describes an infant with physical features typical of leprechaunism, including a characteristic facies, hirsutism, and decreased subcutaneous tissue and muscle mass. Intermittent hypoglycemia and severe hyperinsulinemia were documented. The patient's insulin was normal in molecular size and biological activity, but its binding to the patient's cultured fibroblasts was profoundly decreased. Insulin antibodies were not present. A literature review has been undertaken to clarify further the clinical, metabolic, and pathological characteristics of this condition.
