New Data Evaluates Origin of Pain in Gaucher Disease

Mathew Shanley

A study published in the Orphanet Journal of Rare Diseases confirmed the role played by peripheral neuropathy in Gaucher pain.

A team of researchers led by Grazia Devilgili of the AMC Hosptial of Udine’s Department of Neurology conducted a cross-sectional study intended to investigate the pathophysiology and root of pain in Gaucher disease patients, and whether such pain had a skeletal or neuropathic origin.

The clinic observed the recurrence of painful symptoms in a cohort of type 1 Gaucher (GD1) patients even after a long-term enzyme replacement therapy.

Gaucher disease is a rare genetic condition caused by deficiencies in the glucocerebrosidase enzyme, which is responsible for breaking down fatty substances in the body. Consequently, these substances build up in many of the body’s tissues, including in the bones, organs, and bone marrow, preventing cells and organs from functioning properly.

The rare disease can be categorized into 3 different classifications: type 1, type 2, and type 3 (GD1, GD2, and GD3, respectively). Type 1, also known as non-neuropathic Gaucher disease because the brain and spinal cord are typically unaffected. It is the most common variation of the condition and involves bone disease, anemia, an enlarged spleen and low platelets (thrombocytopenia).

Between the 3 types, Gaucher disease affects an estimated 1 in every 50,000-100,000 people and current treatment options can be incredibly costly to the patient. The pain associated with the disorder often persists despite long-term enzyme replacement, but has been reported even in the absence of bone disease without a clear explanation.

The study enrolled 25 GD1 disease patients (12 males, 13 females) Three patients were newly-diagnosed and 22 others were recipients of enzyme-replacement therapy for a period between 10 and 20 years. Based on electrophysiological examinations, pain was classified as either bone- or neurologically-related.

While pain has generally been poorly studied, yet widely assumed to be associated with skeletal involvement in GD1, results of the study show that it can also present as a late-onset symptom and the result of structural damage to the peripheral nervous system after long-term ERT. This conclusion is largely based the observation that 6 patients in the study reported persistent cold pain despite being on ERT, and the pain was described as being completely different from the pain experienced prior to treatment.

Gaucher Study

Fig. 1
Detail drawing of painful symptoms (a-b) and negative sensory signs (c-d). a and b: the painful area (ongoing cold pain) of two representative GD patients (patients 5 and 8, respectively). c-d: the pinprick hypoalgesia in the same patients. e representative example of the sensory profile at QST at the proximal thigh (patient no. 12) (Z-score). Z-values above “0” indicate a gain, z-value below “0” a loss of sensory function, whereas z-values > ±2 rated pathological. Paradoxycal Heat Sensation (PHS) is here considered as a sign of gain of function.

The authors of the study recommend the need to differentiate between neurological pain so that the proper anti-pain therapy can be prescribed and unnecessary ERT dose escalation can be avoided.

Preventing ERT dose escalation can provide benefit to the patient both financially and as it pertains to disease progression.

Devigili G, De Filippo M, Ciana G, et al. Chronic Pain in Gaucher Disease: Skeletal or Neuropathic Origin? Orphanet Journal of Rare Diseases. 2017;12:148. doi: /10.1186/s13023-017-0700-7
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