Diagnosis

The diagnosis of Gaucher disease is established by a biochemical assay of glucocerebrosidase activity in white blood cells or skin fibroblasts with a reading generally < 30% of normal activity, depending on the laboratory used^[1]. Demonstration of two mutant alleles of the glucocerebrosidase gene provides diagnostic verification^[2].

Bone marrow biopsy has been used to ascertain the presence of Gaucher cells. However, pseudo-Gaucher cells often can lead to misdiagnoses such as chronic myelogenous leukaemia, acute myeloid leukaemia, Niemann-Pick disease, Hodgkin’s disease and centrocytic nodular non-Hodgkin’s lymphoma^[3]. Enzyme assay provides the confirmatory diagnosis.

For more information about laboratories in Belgium where testing for deficient glucocerebrosidase activity can be performed, see LSD specialized laboratories in Belgium

Gaucher disease can pose a challenge to diagnose, despite the availability today of accurate, non-invasive diagnostic tests mentioned above. Misdiagnosis is not unusual and it can delay treatment and thus compromise successful treatment outcomes.

The difficulty arises in part because of the relative rarity of the disease--some practitioners may not even consider testing specifically for it, especially since clinical signs and symptoms may suggest other diseases.^[4,5] Moreover, the disease's clinical course can be unpredictable; signs and symptoms may take years to emerge and may progress at varying rates,^[4,5] further complicating the question of which tests to order.

Many of Gaucher disease's presenting symptoms--from distended abdomen to bone pain to hematological complications--are found with other more common diseases. Thus it's not unusual for physicians to suspect other disorders and initially misdiagnose Gaucher patients. Some of the most common misdiagnoses include: ^[6]

Leukemia

Lymphoma

Bleeding disorders

Osteomyelitis

Legg-Calvé-Perthes

References

1. Aerts JMFG, Boot RG, Renkema GH, et al: Molecular and biochemical abnormalities of Gaucher disease: chitotriosidase, a newly identified biochemical marker. Seminars in Hematology 32(3, suppl 1):10-13, 1995

2. Duursma SA, Aerts JMFG, Belmatoug N, et al: Management of Gaucher disease. Current status and future directions. A roundtable discussion. Seminars in Hematology 32(3, suppl 1):45-52, 1995

3. Alterini R, Rigacci L, Stafanacci S: Pseudo-Gaucher cells in the bone marrow of a patient with centrocytic nodular non-Hodgkin’s Lymphoma. Haematologica 81:282-283, 1996

4. Beutler E, Grabowski G. Gaucher disease. In:Scriber CR, Beaudet AL, Sly WS, et al, eds. The Metabolic and Molecular Bases of Inherited Disease. 7th ed. New York, NY: McGraw-Hill; 1995;2:2641-2661.

5. Cox TM, Schofield JP. Gaucher's disease: clinical features and natural history. Bailliere's Clinical Haematology. 1997;10(4):657-689.

6. Grabowski GA. Lysosomal storage diseases. In: Braunwald E, Fauci AS, eds. Harrison's Principles of Internal Medicine. 15th ed. New York, NY: McGraw-Hill; 2001:2276-2281.