Correct statements concerning inherited defects of metabolism include which of the following?
ExplanationD. In Niemann-Pick disease, accumulation of sphingomyelins occurs usually because of a sphingomyelinase deficiency. Organomegaly and neurologic involvement are clinical features, but there is highly variable expression that depends on the subtype. The most common lysosomal storage disease, adult Gaucher disease, is characterized by splenomegaly, pancytopenia, hepatic dysfunction, and bone pain. Accumulation of glucosylceramides presumably accounts for the clinical manifestations and for the distinctive Gaucher cell observed on bone marrow examinations. TaySachs disease, which is caused by a deficiency of hexosaminidase A with concomitant accumulation of sphingolipids, presents as rapidly progressive neurologic deterioration during infancy and with a characteristic macular cherry-red spot. Heterozygote detection programs (enzyme assays in Ashkenazi Jews) have reduced the incidence of this disease in North America. Diseases of glycogen metabolism can result in disorders whose pathophysiology is based either on hepatic hypoglycemia, as in von Gierke’s disease (glucose-6-phosphatase deficiency), or on muscle-energy deficiency, as in McArdle disease (muscle phosphorylase deficiency). Muscle-energy diseases generally result in painful cramping or myoglobinemia after exercise, and so strenuous exercise should be avoided. These diseases are otherwise compatible with a normal life. A defect in the phenylalanine hydroxylase enzyme complex leads to accumulation of phenylalanine in blood and urine with associated brain damage. The plasma phenylalanine concentration usually does not rise until the institution of protein feedings but is abnormal by the fourth day of life. A diet low in phenylalanine, if instituted during the first month of life, can avert mental retardation. Screening all newborns for blood phenylalanine concentration has been beneficial in this regard. Excessive urinary excretion of the dibasic amino acids cysteine, lysine, arginine, and ornithine as a result of impaired tubular reabsorption is the pathophysiologic hallmark of cystinuria, the most common inborn error of amino acid transport. Because of the insolubility of cysteine, the primary clinical manifestation of this disorder is cysteine nephrolithiasis.
