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General Reference ⬇

Nejm 1991;325:1354 (Gaucher’s Disease); Ann IM 1975;82:257 (all)

Pathophys and Cause ⬆ ⬇

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) rtarrow.gif 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

Epidemiology ⬆ ⬇

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

Signs and Symptoms ⬆ ⬇

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

Course ⬆ ⬇

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

Complications ⬆ ⬇

GD, pulmonary hypertension (Ann IM 1996;125:901)

r/o carnitine deficiency, presents as Reye's syndrome (Nejm 1980;303:1389)

Lab and Xray ⬆ ⬇

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

Treatment ⬆

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)