Diagnostic and confirmatory testing

Gaucher disease is a rare condition with signs and symptoms that can be confused with those of many other conditions. However, a number of tests allow definitive diagnosis of the condition.

 

Enzyme assay

Gaucher disease is caused by a significant reduction of the enzyme acid-β glucosidase. Enzyme activity of acid-β glucosidase can be measured using a dry blood spot (DBS) sample. However, the gold standard for the diagnosis of Gaucher disease is the demonstration of reduced acid-β glucosidase activity in peripheral leukocytes, cultured fibroblasts or amniotic fluid cells. Machaczka M, Markuszewska-Kuczyńska A, Regenthal S, Jurczyszyn A, Gałązka K, Wahlin BE, Klimkowska M. Clinical utility of different bone marrow examination methods in the diagnosis of adults with sporadic Gaucher disease type 1. Pol Arch Med Wewn. 2014;124(11):587-92. Enzymatic assays do not differentiate between the different types of Gaucher disease.

 

Molecular diagnosis

DNA testing can be used to aid diagnosis and screen for carrier status. Although many genetic mutations associated with Gaucher disease have now been identified, a negative result does not necessarily guarantee the absence of a Gaucher disease allele. However, there are some well-established associations that have been identified, particularly in the Ashkenazi Jewish population. In this group approximately 1 in 17 individuals is a carrier of the acid-β glucosidase gene 1 (GBA1) mutation. Kaplan P, Baris H, De Meirleir L, Di Rocco M, El-Beshlawy A, Huemer M, et al. Revised recommendations for the management of Gaucher disease in children. Eur J Pediatr 2013;172:447-58.  Two mutations account for up to 80-90% of mutations seen in Ashkenazi Jewish patients with Gaucher disease: N370S and 84GG. L444P and N370S mutations account for over half of the mutations seen in non-Jewish white patients. 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.

 

Histological

The classical method for diagnosing Gaucher disease was detection of the lipid-engorged Gaucher cell in bone marrow aspirate, liver biopsy or a surgically removed spleen. However, very similar cells (termed pseudo-Gaucher cells) have been described associated with a number of other diseases including: 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.

  • chronic granulocytic leukemia
  • acute lymphocytic leukemia
  • lymphomas
  • thalassemia
  • multiple myeloma
  • Hodgkin disease 

Biochemical and molecular techniques are more specific and less invasive and routine histological assessment is now discouraged. 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.

 

Biochemical markers 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, 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.

A number of macrophage-specific enzymes are elevated in the plasma of patients with Gaucher disease and some can be used as biomarkers in routine monitoring. The finding of elevated levels of one or more of these markers is never sufficient to diagnose Gaucher disease since these markers may be elevated in other disorders. These biomarkers include:

  • Chitotriosidase
  • Angiotensin-converting enzyme
  • Tartrate-resistant acid phosphatase

In addition, raised levels of ferritin, low vitamin B12 and hypocholesterolemia are commonly found in patients with Gaucher disease. However, the biomarkers mentioned in this section are not sufficient or required to make a definitive diagnosis of Gaucher due to their association with a range of other disorders.