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?
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.
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
Genetics