Neurological manifestations in patients with Gaucher disease and their relatives, it is just a coincidence?

Gaucher disease (GD) is an autosomal recessive disorder characterized by defective function of glucocerebrosidase. GD presents a wide spectrum of manifestations, and patients and their relatives may develop neurological abnormalities more frequently than the general population. This study aims to determine the presence of neurological symptoms (NS) and Parkinson's disease (PD) in Spanish GD patients and their relatives. We surveyed 87 GD Spanish families and validated the information obtained on the neurological involvement through their physicians, as well as the historical data included in the Spanish Gaucher Disease Registry. Neurological abnormalities were correlated with the genetic characteristics. Statistical analyses included descriptive parameters, ANOVA, t-test, correlation study and Pearson coefficient. Information was obtained from 118 patients and 324 relatives. Out of 110 patients with type 1 GD, 32 (29.1%) reported NS and 7 (6.4%) had PD. In relatives, a total of 39 (13.1%) subjects had NS, including 16 with PD (5.3%). The prevalence of NS in genetic carriers (15.9%) was greater than that in non-carriers (5.9%; p < 0.01). Patients with PD carried the following GBA mutations: S364R, D409H, L444P, R257Q, IVS4-2A > G, c.500insT, and L336P. Relatives with PD exhibited a wide spectrum of mutations: L444P, N370S, V398I, R257Q, G202R, c.1439-1445del7, [E326K; N188S], and c.953delT. We observed a high incidence of PD in type 1 GD and relative's carriers. PD was more frequent in carriers of L444P and other rare GBA mutations. Therefore, it is important to perform a systematic neurological exam in patients with type 1 GD and carriers with high risk mutations.

Neurologic improvement in a type 3 Gaucher disease patient treated with imiglucerase/miglustat combination.

PURPOSE: Gaucher disease (GD) is an autosomal recessive lysosomal disorder caused by a deficiency of glucocerebrosidase. The neurologic manifestations of GD patients have to date been refractory to any treatment approach. We present a report of a neuronopathic GD patient whose myoclonic epilepsy improved after combination therapy with imiglucerase and miglustat. METHODS: In an adult type 3 GD patient who, despite good visceral and analytic response to ERT, developed progressive neurologic deterioration with marked myoclonic epilepsy and dystonia, we added miglustat to the enzyme-replacement therapy. RESULTS: After 2 years of combined miglustat (200 mg, 3 t.i.d.) and imiglucerase (60 IU/kg every 2 weeks), generalized tonic-clonic seizures decreased, speech improved, and the general neurologic clinical picture improved markedly. The EEG showed a reduction in focal and generalized paroxysmal discharges. No significant adverse effects were observed. CONCLUSIONS: Combined imiglucerase and miglustat therapy may be beneficial for some neuronopathic forms of GD.