Pompe disease in Austria: clinical, genetic and epidemiological aspects.

In this study, we performed a survey of infantile and late-onset Pompe disease (IOPD and LOPD) in Austria. Paediatric and neuromuscular centres were contacted to provide a set of anonymized clinical and genetic data of patients with IOPD and LOPD. The number of patients receiving enzyme replacement therapy (ERT) was obtained from the pharmaceutical company providing alglucosidase alfa. We found 25 patients in 24 families, 4 IOPD and 21 LOPD with a resulting prevalence of 1:350,914. The most frequent clinical manifestation in LOPD was a lower limb-girdle phenotype combined with axial weakness. Three patients were clinically pauci- or asymptomatic and were diagnosed because of persistent hyperCKemia. Diagnostic delay in LOPD was 7.4 ± 9.7 years. The most common mutation was c.-32-13T > G. All IOPD and 17 symptomatic LOPD patients are receiving ERT. Standardized follow-up was only available in six LOPD patients for the 6-min walk test (6minWT) and in ten for the forced vital capacity (FVC). Mean FVC did not decline (before ERT; 63.6 ± 39.7%; last evaluation during ERT: 61.9 ± 26.9%; P = 0.5) while there was a trend to decline in the mean distance covered by the 6minWT (before ERT: 373.5 ± 117.9 m; last evaluation during ERT: 308.5 ± 120.8 m; P = 0.077). The study shows a lower prevalence of Pompe disease in Austria than in other European countries and corroborates a limb-girdle phenotype with axial weakness as the most common clinical presentation, although asymptomatic hyperCKemia may be the first indication of LOPD.

Causally treatable, hereditary neuropathies in Fabry's disease, transthyretin-related familial amyloidosis, and Pompe's disease.

OBJECTIVES: Most acquired neuropathies are treatable, whereas genetic neuropathies respond to treatment in Fabry's disease (FD), transthyretin-related familial amyloidosis (TTR-FA), and Pompe's disease (PD). This review summarizes and discusses recent findings and future perspectives concerning etiology, pathophysiology, clinical presentation, diagnosis, treatment, and outcome of neuropathy in FD, TTR-FA, and PD. METHODS: Literature review. RESULTS: Neuropathy in FD concerns particularly small, unmyelinated, or myelinated sensory fibers (small fiber neuropathy [SFN]) and autonomic fibers, manifesting as acroparesthesias, Fabry's crises, or autonomous disturbances. FD neuropathy benefits from agalsidase alpha (0.2 mg/kg every second week intravenously) or from beta (1.0 mg/kg every second week intravenously). Neuropathy in TTR-FA is axonal and affects large and small sensory, motor, and autonomous fibers. Neuropathy in TTR-FA profits from liver transplantation and the TTR kinetic stabilizer tafamidis (20 mg/d). Neuropathy in PD particularly occurs in late-onset PD and manifests as mononeuropathy, polyneuropathy, or SFN. PD neuropathy presumably responds to alglucosidase-alpha (20 mg/kg every second week intravenously). CONCLUSIONS: Neuropathy in FD, TTR-FA, and PD is predominantly a SFN and can be the dominant feature in FD and TTR-FA. SFN in FD, TTR-FA, and PD needs to be recognized and benefits from enzyme replacement treatment or TT-kinetic stabilizers.

Iatrogenic lesions of peripheral nerves.

Iatrogenic nerve lesions (INLs) are an integral part of peripheral neurology and require dedicated neurologists to manage them. INLs of peripheral nerves are most frequently caused by surgery, immobilization, injections, radiation, or drugs. Early recognition and diagnosis is important not to delay appropriate therapeutic measures and to improve the outcome. Treatment can be causative or symptomatic, conservative, or surgical. Rehabilitative measures play a key role in the conservative treatment, but the point at which an INL requires surgical intervention should not be missed or delayed. This is why INLs require close multiprofessional monitoring and continuous re-evaluation of the therapeutic effect. With increasing number of surgical interventions and increasing number of drugs applied, it is quite likely that the prevalence of INLs will further increase. To provide an optimal management, more studies about the frequency of the various INLs and studies evaluating therapies need to be conducted. Management of INLs can be particularly improved if those confronted with INLs get state-of-the-art education and advanced training about INLs. Management and outcome of INLs can be further improved if the multiprofessional interplay is optimized and adapted to the needs of the patient, the healthcare system, and those responsible for sustaining medical infrastructure.