Background: In a rare Gaucher disease, reduced activity of lysosomal b-glucocerebrosidase incompletely blocks glucosphingolipid catabolism. Accumulation of the unhydrolyzed substrate glucosylceramide within lysosomes results in progressive, multisystem Gaucher disease, classified into three types. Both parkinsonism and peripheral neuropathy are observed in cases of putative non-neuronopathic type 1 disease. In the current study we investigated whether the peripheral neural response in type 1 Gaucher disease patients, with no neural manifestations is conditioned by the influence of sex hormones.
Methods: The catalytic activity of b-glucocerebrosidase in peripheral blood leukocytes was determined spectrofluorometrically. Direct sequencing of the GBA1 gene was performed. Somatosensory evoked potentials were recorded after electrical stimulation of the median nerve of both arms. Stimuli of 0.2 ms duration at a frequency of 5 Hz were used. Sex hormones were determined by radioimmunoassay using a gamma scintillation counter.
Results: Analysis of the somatosensory evoked potentials revealed significant differences in peak latencies on periphery between men and women in both control and type 1 Gaucher disease groups. Analysis by gender showed significant associations between latencies and sex hormones only in female patients: negative correlation between oestradiol concentration and N9 peak latency, and a strong negative correlation of testosterone levels with all peak latencies on the periphery (N9-N13).
Conclusions: A relationship between testosterone concentrations and the latencies of potentials evoked on peripheral nerves exists only in females with type 1 Gaucher disease. We point out sexual dimorphism in the development of this entity.
Uvod: Kod retke Gošeove bolesti, snižena aktivnost lizozomske b-glikocerebrozidaze uzrokuje nepotpuni blok katabolizma glikosfingolipida. Nagomilavanje nehidrolizovanog supstrata glukozilceramida u lizozomima dovodi do progresivne, multisistemske Gošeove bolesti klasifikovane u tri tipa. Ispostavilo se da se kod obavezno ne-neuronopatskog tipa 1 ipak javlja neuralna patologija - parkinsonizam i periferna neuropatija. U aktuelnoj studiji, istraživali smo da li je kod pacijenata sa Gošeovom bolešću tipa 1 koji su bez ikakvih neuroloških manifestacija periferni neuralni odgovor uslovljen uticajem polnih hormona.
Metode: Katalitička aktivnost b-glikocerebrozidaze u leukocitima periferne krvi utvrđena je spektrofluorometrijskim metodom. Analiza gena GBA1 izvedena je direktnim sekvenciranjem. Snimljeni su somatosenzorni potencijali evocirani električnom stimulacijom nervusa medijanusa obe ruke. Nadražajima trajanja 0,2 ms delovalo se frekvecijom od 5 Hz. Polni hormoni su mereni radioimunološkim metodom pomoću gama scintilacionog brojača.
Rezultati: Metodom somatosenzornih evociranih potencijala otkrili smo značajnu razliku u latencama kod muškaraca i žena na periferiji, kako u kontrolnoj grupi tako i u grupi Gošeove bolesti tipa 1. Analiza po polu pokazuje značajne korelacije između latenci i polnih hormona samo kod ženskih pacijenata: značajno negativnu korelaciju između koncentracije estradiola i latence N9, i jaku negativnu korelaciju nivoa testosterona sa svim latencama na periferiji (N9-N13).
Zaključak: Dokazom da povezanost koncentracija testosterona i latenci potencijala izazvanih na perifernim živcima postoji samo kod žena sa tipom 1 Gošeove bolesti ukazujemo na seksualni dimorfizam u razvoju toga entiteta.
Keywords: Type 1 Gaucher disease; latencies; oestradiol; somatosensory evoked potentials; testosterone.
2020 Milan B. Lakočević, Mirjana M. Platiša, Zorica R. Šumarac, Nada D. Suvajdžić, Lana Đ. Mačukanović, Milan S. Petakov, published by CEON/CEES.