The research, “Polyneuropathy in Gaucher disease type 1 and 3 – a descriptive case series,” was published in Nature Scientific Reports.
Gaucher disease type 3 (GD3) is characterized by variable disease severity and complications within and outside the central nervous system (CNS, consisting of the brain and spinal cord). However, the most common form, GD1, has typically been regarded as not affecting the CNS, as its symptoms are secondary to involvement of internal organs such as the lungs and heart. Yet, people with GD1 are at an increased risk for developing Parkinson’s disease.
In recent years, several studies have shown an increased prevalence of polyneuropathy in people with GD1. In these patients, polyneuropathy refers to damage in peripheral nerve fibers that control sensation and movement.
Deficient levels of vitamin B12 (or cobalamin) is a known cause of polyneuropathy. Cellular processes induced by vitamin B12 depend on its entry into the lysosome, a cellular structure that contains enzymes that break down excess or worn-out cell parts. Glucocerebrosidase, key for the metabolism of fat molecules known as glycosphingolipids, is an enzyme found in lysosomes but is deficient in GD patients.
In the study, researchers investigated polyneuropathy and vitamin B12 status in 19 GD patients in Sweden. Eight had GD1 (median age of 54 years) and 11 had GD3 (39 years).
All participants underwent clinical assessments and blood sample analyses. The researchers also performed nerve conduction studies, as well as quantitative sensory testing in the feet and one hand, in patients who had symptoms or clinical findings indicative of polyneuropathy.
Results of sensory tests revealed small fiber neuropathy (SFN) in two GD1 patients, which is characterized by severe pain attacks that typically begin in the feet or hands. In both patients, SFN was subclinical, meaning that it did not present recognizable clinical findings.
Three patients with GD1 had large fiber polyneuropathy, which could not be associated with GD itself. Of note, large fibers carry messages to muscles that control movement, and information related to touch, vibration, and balance.
No GD3 patient showed evidence of either small or large fiber polyneuropathy that could be attributed to the disease.
The findings also showed no differences in neuropathy rating scores comparing Gaucher patients with data from 11 controls (median age of 64 years) with no previous diagnosis of polyneuropathy.
“In summary, our study does not support large fiber PNP [polyneuropathy] as a prevalent manifestation of GD. SFN is a possible feature in GD1, although small sample size limits definite conclusions,” the researchers wrote.
“Our study provides novel data, arguing against clinically significant small or large fiber PNP in GD3,” they added.
As only one asymptomatic patient showed deficient vitamin B12 function, the research also does not support a link between PNP and cobalamin deficiency in GD, the team said.