[Philippe Charles Ernest Gaucher (1854–1918), French dermatologist]

= rare autosomal recessive / dominant (in a few) lipid storage disorder; the most common lysosomal storage disorder;

Prevalence: 1÷50,000–100,000 (general population); 1÷500–1,000 (in Ashkenazi Jews); M = F

Etiology: deficiency of lysosomal hydrolase acid β-glycosidase (= b-glucocerebrosidase) → accumulation of glucosylceramide (glucocerebroside) within macrophages of RES (liver, spleen, bone marrow, lung, lymph nodes)

Histo: bone-marrow aspirate shows Gaucher cells (kerasin-laden histiocytes) of 20–100 µm in diameter with a foamy wrinkled-paper appearance

Clinical types:

1. Adult / chronic nonneuropathic form = type 1 (most common form in USA)
   Age of onset: 3^rd–4^th decade
   • no clinical signs (most)
   
   Prognosis: longest time of survival; pulmonary involve-ment / hepatic failure may lead to early death
2. Rapidly fatal infantile / acute neuropathic form = type 2
   Age of onset: 1–3–12 months
   • early onset of significant hepatosplenomegaly
   • severe progressive neurologic symptoms: seizures, mental retardation, strabismus, spasticity
   • skeletal manifestations are rare
   
   Prognosis: fatal during first 2 years of life
3. Juvenile / subacute neuropathic form = type 3 (rarest type)
   Age of onset: 2–6 years
   • variable hepatosplenomegaly
   • mild neurologic involvement: seizures
   • delayed onset of skeletal manifestations
   
   Prognosis: survival into adolescence

• hepatosplenomegaly, impairment of liver function, ascites
• elevated serum acid phosphatase
• pancytopenia, anemia (chronic fatigue), leukopenia, thrombocytopenia (easy bruising, hypersplenism)
• hemochromatosis (yellowish brown pigmentation of conjunctiva + skin)
• dull bone pain (bone involvement in 75%)

Location: predominantly long tubular bones (distal femur), axial skeleton, hip, shoulder, pelvis; bilateral

• generalized osteopenia (decrease in trabecular bone density):
  • striking cortical thinning + bone widening
  • endosteal scalloping ← marrow packing
• numerous sharply circumscribed lytic lesions resembling metastases / multiple myeloma (marrow replacement)
• periosteal reaction = cloaking
• Erlenmeyer flask deformity of distal femur + proximal tibia ← marrow infiltration (MOST CHARACTERISTIC)
• weakening of subchondral bone:
  • osteonecrosis (common, frequently of femoral head)
  • degenerative arthritis
• bone infarcts in long-bone metaphyses (most common in femoral + humeral heads):
  • focal / serpentine areas of sclerosis
  • bone-within-bone appearance
• H-shaped / “step-off” / biconcave “fish-mouth” vertebrae (DDx: sickle cell disease)

MR:

• focal / diffuse replacement of adipocytes in bone marrow by Gaucher cells results in decreased marrow signal on T1WI + T2WI (marrow involvement follows the distribution of hematopoietic marrow in spine, pelvis, proximal femoral metaphysis; from proximal to distal in appendicular skeleton):
  • epiphyses generally not involved
• myelofibrotic marrow of low SI on T1WI + T2WI (in long-standing disease)

• Liver
  • hepatomegaly
  • nonspecific fatty + cirrhotic changes
  • focal lesions hypointense on T1WI + hyper- to isointense on T2WI
• Spleen
  • splenomegaly + lymphadenopathy
  • multiple nodular lesions (= clusters of RES cells laden with glucosylceramide):
    • hypodense without enhancement on CT
    • hypoechoic / hyperechoic on US
    • slightly hypo- to isointense on T1WI
    • hypointense (Gaucher cells / fibrosis) or hyperintense (dilated sinusoids filled with blood around Gaucher cell infiltrates) on T2WI
  • splenic infarcts leading to fibrosis, especially in massively enlarged spleen
• Lung
  • normal
  • nonspecific diffuse reticulonodular / miliary infiltrates at lung bases (= infiltration with Gaucher cells)

Dx: elevated serum activity of β-glucocerebrosidase; genotyping

Cx:◊>90% have orthopedic complications at some time

1. Pathologic fractures + compression fractures of vertebrae
2. Avascular necrosis of femoral head, humeral head, wrist, ankle (common)
3. Osteomyelitis (increased incidence)
4. Myelosclerosis in long-standing disease
5. Repeated pulmonary infections
6. Cancer of hematopoietic origin (14.7-fold risk)

Prognosis: highly variable clinical course; strong relationship between splenic volume and disease severity

Rx: no cure; bone marrow transplantation; enzyme replacement therapy with Cerezyme^®

DDx: metastatic disease, multiple myeloma, leukemia, sickle-cell disease, fibrous dysplasia