Résumé :
|
SBMA is rare, adult onset, X-linked recessive disease caused by CAG repeat expansion in AR gene. The main symptoms due to lower motor neuron involvement comprise slowly progressive weakness of extremity and bulbar muscles, fasciculation, cramps and tremor. Gynecomastia and reduced fertility are often observed. No causal therapy is available up to day. The aim of our study was to clinically characterize 15 Polish patients with genetically confirmed SBMA. Material: Patients with CAG repeat expansion in AR gen were indentified in the period 1995-2010. Methods: We assessed retrospectively the clinical history, laboratory findings and pedigrees of patients. Molecular test was performed by amplification of region containing CAG repeat expansion in PCR reaction with specific primers. Results: A mean age of onset was 45y. (range 27-62), an average age of evaluation was 51y. (range 31-62), a mean duration of disease was 7 y. (range 1-16). Proximal muscle weakness was the most frequent first symptom. Cramps and fasciculation were observed in 25% of patients at the beginning of disease. The most frequent symptoms at evaluation was proximal muscle weakness and atrophy, bulbar symptoms and fingers tremor. Gynecomastia was observed in 7 patients. CK level was mildly elevated in most patients and very high in only one. Testosterone level was essentially abnormal only in one case. EMG showed chronic neurogenic changes in most cases. Axonal sensory nerves impairment was observed on ENG in almost all cases. 6 patients were familiar cases and their pedigrees were consisted with X-linked recessive inheritance. All patients except one had an offspring. The range of CAG repeat was 41-51, with a mean of 46. An inverse correlation between age of onset and CAG repeat length as well as a weak positive correlation between severity of symptoms and number of CAG repeats was found. Only in 5 patients SBMA diagnosis was established at the onset; in other cases SLA, CMT or SMA were considered as a primary diagnosis. Conclusions: Phenotypic variability observed in our patients is consistent with that described in the literature. Diagnosis of SBMA, especially in an early phase of the disease, can be difficult because of lack of a full spectrum of symptoms and absence of specific markers. Detailed analysis of genetic and clinical data of patients with rare neuromuscular disease allows to create databases beneficial in planning future clinical trials.
|