Rare etiology of autosomal recessive disease in a child with noncarrier parents.

A child with maple syrup urine disease type 2 (MSUD2) was found to be homozygous for a 10-bp MSUD2-gene deletion on chromosome 1. Both purported parents were tested, and neither carries the gene deletion. Polymorphic simple-sequence repeat analyses at 15 loci on chromosome 1 and at 16 loci on other chromosomes confirmed parentage and revealed that a de novo mutation prior to maternal meiosis I, followed by nondisjunction in maternal meiosis II, resulted in an oocyte with two copies of the de novo mutant allele. Fertilization by a sperm that did not carry a paternal chromosome 1 or subsequent mitotic loss of the paternal chromosome 1 resulted in the propositus inheriting two mutant MSUD2 alleles on two maternal number 1 chromosomes.

Management of hypercholesterolemia in childhood and adolescence.

There is strong evidence that the onset of atherosclerosis occurs in childhood. Identifying and treating children and adolescents at risk for hypercholesterolemia should lead to a decrease in adult atherosclerotic disease. Based on current information, and the National Cholesterol Education Program (NCEP) guidelines, screening in children and adolescents should be limited to those individuals with specific cardiac risk factors or those from families with a strong history of atherosclerotic disease. Treatment of identified patients should be initiated with dietary control. Subsequent use of cholesterol-lowering medication is best limited to those patients who fail at least 6 months of dietary control measures. Drug therapy includes the use of bile acid sequestrants, nicotinic acid and, more recently, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors. There has been limited experience with HMG CoA reductase inhibitors in children and adolescents. However, preliminary data suggests that they are both more effective and have less side effects than either bile acid sequestrants or niacin. Long-term cohort studies will be needed to determine whether screening and treating children and adolescents with hypercholesterolemia is truly of long-term benefit and, if so, which treatment strategies will be preferred.