Differential diagnosis

The ability to correctly differentiate Gaucher disease from other disorders is crucial to minimize diagnostic delays and optimize patient outcomes. However, diagnosis of Gaucher disease can be a challenging task due to its rarity, its unpredictable and variable clinical course and the fact that many of its clinical signs and symptoms could suggest other diseases. Grabowski GA, Petsko GA, Kolodny EH. Chapter 146: Gaucher disease. Valle D, Beaudet AL, Vogelstein B, et al, eds. The Online Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw Hill; 2013. Accessed July 6, 2015.

Mistry PK, Sadan S, Yang R, Yee J, Yang M. Consequences of diagnostic delays in type 1 Gaucher disease: the need for greater awareness among hematologists-oncologists and an opportunity for early diagnosis and intervention. Am J Hematol 2007;82:697–701.
 Despite the availability of definitive diagnostic tests which include enzyme activity assays and DNA analysis, considerable delays in diagnosis are quite common.

When a patient presents with Gaucher disease, a number of other disorders could initially be suspected. Mistry PK, Sadan S, Yang R, Yee J, Yang M. Consequences of diagnostic delays in type 1 Gaucher disease: the need for greater awareness among hematologists-oncologists and an opportunity for early diagnosis and intervention. Am J Hematol 2007;82:697–701.  These could include:

  • leukemia
  • lymphoma
  • bleeding disorders
  • multiple myeloma

Splenomegaly is a key presenting sign of Gaucher disease and is present in the vast majority of Gaucher patients. Kaplan P, Andersson HC, Kacena KA, Yee JD. The clinical and demographic characteristics of non-neuronopathic Gaucher disease in 887 children at diagnosis. Arch Pediatr Adolesc Med 2006;160:603–8.  A number of other signs and symptoms are particularly indicative of Gaucher disease and should be followed-up immediately:

  • doctors should consider the diagnosis of type 1 Gaucher disease (non-neuronopathic) in any patient presenting with unexplained splenomegaly with or without skeletal manifestations, hepatomegaly and bleeding diathesis. Mistry PK, Abrahamov A. A practical approach to diagnosis and management of Gaucher’s disease. Bailliere's Clinical Haematology. 1997;10(4): 817-838.
  • children presenting with hepatosplenomegaly and neurological symptoms should also be assessed for types 2 or 3 Gaucher disease. Mistry PK, Abrahamov A. A practical approach to diagnosis and management of Gaucher’s disease. Bailliere's Clinical Haematology. 1997;10(4): 817-838.

An international group recently published useful diagnostic algorithms that show the frequencies of disorders associated with splenomegaly. Mistry PK, Cappellini M, Lukina E, et al. Consensus Conference: a reappraisal of Gaucher disease – diagnosis and disease management algorithms. Am J Hematol 2011;86(1):110-115.

Suggested diagnostic algorithm for individuals of non-Ashkenazi Jewish origin.

Diagnostic algorithm Gaucher - Mistry

Adapted from Mistry PK, et al, 2011 Mistry PK, Cappellini M, Lukina E, et al. Consensus Conference: a reappraisal of Gaucher disease – diagnosis and disease management algorithms. Am J Hematol 2011;86(1):110-115.

 

High-risk populations

High-risk populations worthy of further diagnostic investigations for Gaucher disease include siblings of individuals with the disease and those with Ashkenazi Jewish ancestry. Population screening may be appropriate in some populations including in Norrbottnia, Sweden, or the Arab populations in the Jenin and Gaza regions of Palestine where there is high prevalence of type 3 disease. Mistry PK, Abrahamov A. A practical approach to diagnosis and management of Gaucher’s disease. Bailliere's Clinical Haematology. 1997;10(4): 817-838.