Cause:
Genetic, autosomal recessive
Gaucher's (GD) on chromosome 21
Pathophys:
Neurologic disorder due to distention of neuron with lipid, displacement of nucleus toward axon hillock. All cause enlargement of RES organs, bone involvement, etc. General increase in brain size. All have a defective catabolic enzyme
NPD has cholesterol and sphingomyelin foam cells
GD has an enzyme defect at glucosylceramide (a glucocerebroside) sphingosine + folic acid (Nejm 1971;284:739)
TSD has ganglioside foam cells due to hexosaminidase A deficiency (Nejm 1970;282:15)
Wolman's disease (WD) has cholesterol foam cells exclusively in RES
Niemann-Pick (NPD): children age 2-5 yr
GD: children and adults, esp in Jews (1/850)
Tay-Sachs (TSD): Jews only, gene prevalence 1/30 Ashkenazi Jews
Sx:Bone pain, fractures, failure to thrive, and seizures
Si: Pathologic fractures; neurologic si's, large head, seizures, amaurosis; cherry red macular spot; splenomegaly, anemia, bleeding; pingueculae
NPD and GD: most die before age 5 yr
TS die before age 5 yr, although one gene type presents in adolescence
WD present and die by age 3 mo
GD, pulmonary hypertension (Ann IM 1996;125:901)
r/o carnitine deficiency, presents as Reye's syndrome (Nejm 1980;303:1389)
Lab:
Chem:GD, elevated acid phosphatase, nonprostatic portion, increased B12-binding proteins (Nejm 1976;295:1046)
TSD, increased AST (SGOT), hexosaminidase A absent in homozygote, intermediate levels in heterozygote (Nejm 1970;283:15)
Hem:GD, low platelets (hypersplenism)
Path:NPD, nerve biopsy shows foam cells; GD, marrow shows foam cells, spindle-shaped with eccentric nuclei; WD, RES biopsy shows foam cells
Urine:24-h collection analyzed for glycoceramide (Nejm 1971;284:739)
Xray:Erlenmeyer flask-like lesion, lucent, often in lower femur
Rx:
NPD, genetic counseling by detecting heterozygote (Nejm 1974;291:989)
GD, genetic counseling; splenectomy helps CBC but may speed course; marrow transplant (Nejm 1993;328:745); or iv enzyme, alglucerase (Ceredase) (Ann IM 1994;121:196; Nejm 1992;327:1632; 1991;324:1464), which costs $250 000-$500 000/yr, or recombinant type (Cerezyme) (Ann IM 1995;122:33)
TSD, screen serum or tears with hexosaminidase-based test (Nejm 1973;289:1072), confirm with DNA-based test (Nejm 1990;323:6)