Abstract

Aims: Gaucher disease (GD) is characterized by a wide spectrum of manifestations. Several reports have indicated that GD relatives could developed neurological abnormalities. In order to detect neurological symptoms in GD patients and their relatives we have designed a specific prospective inquiry in Spanish GD families.

Patients and Methods: the Spanish GD Registry is an independent registry working since 1993, sponsored by the Spanish Gaucher Foundation (FEETEG). From January to December 2006 we have perform a postal survey contacting 42 physicians and 92 families to evaluate neurological symptoms and correlated with genetic characteristics. The data were included in a SPSS 12.0 data base to perform statistical analysis using descriptive parameters, ANOVA, t-test and correlation study including Pearson coefficient.

Results: We have obtained information from 72 families (78.3% responses) that included 92 type 1 and 7 type 3 GD patients and 266 relatives. Thirty (32.6%) of type 1 GD reported any neurological problem: tremor 8 (8.7%), uncordinated movements 9 (13.8%), concentration defects 11 (11.9%), strabismus 7 (7.6%), deafness 8 (8.7%), Parkinson disease (PD) 7 (7.6%), peripheral neuropathy 10 (10.9%). Thirty six (13.5%) first or second degrees relatives from 72 families presented neurological manifestations: PD 14 (5.3%), epilepsia 8 (3.0%), tremor 7 (2.6%), deafness 2 (0.7%), others 5 (1.9%). Patients with PD had mutations: S364R, D409H, L444P, [IVS2-2A>G]+ [c.(− 203)A>G], c.500insT, L336P. In relatives with PD a wide spectrum of mutations were observed: L444P, N370S, V398I, G202R, c.1439–1445del7, [E326K]+[N188S] and c.953delT, in others neurological manifestations as epilepsia, tremor or peripheral neuropathy predominant mutations were D409H, G195W, R120W; R147X, L336P and G377S.

Conclusions: We have found a higher incidence than expected of PD and other neurological symptoms in GD1 patients and relatives. These manifestations appear frequently in carriers of L444P or rare mutations. It is important to perform a systematic neurological exam in GD1 patients and carriers with risk mutations. This work is partially supported by the grant FIS: 06/1253.

Author notes

Disclosure: No relevant conflicts of interest to declare.