A 22-year-old woman delivers an apparently healthy female infant after an uncomplicated pregnancy. By 4 years of age, the girl has progressive, severe neurologic deterioration. Physical examination shows marked hepatosplenomegaly. A bone marrow biopsy specimen shows numerous foamy vacuolated macrophages. Analysis of which of the following factors is most likely to aid in the diagnosis of this condition?
Level of a1-antitrypsin in the serum
Level of glucose-6-phosphatase in hepatocytes
Level of sphingomyelinase in splenic macrophages
Number of LDL receptors on hepatocytes
The clinical features of this child neurologic involvement, hepatosplenomegaly, and accumulation of foamy macrophages - suggest a lysosomal storage disorder. One such disorder, with which the clinical history is quite compatible, is Niemann-Pick disease type A. It is characterized by lysosomal accumulation of sphingomyelin owing to a severe deficiency of sphingomyelinase. Globules of a1 -antitrypsin are seen in the liver cells of individuals with inherited deficiency of a1 -antitrypsin. The glycogen storage disease known as von Gierke disease results from glucose-6-phosphatase deficiency. In familial hypercholesterolemia, there are fewer LDL receptors on hepatocytes, leading to early and accelerated atherosclerosis by young adulthood. Collagen synthesis is impaired in individuals with Ehlers-Danlos syndrome.
Genetics