J.M. de Vries

P.17.1 Phenotypic variation within 22 families with Pompe disease

Pompe disease is an autosomal recessive disorder caused by a deficiency of acid α -glucosidase (GAA) leading to glycogen accumulation in different tissues. Pompe disease has a broad clinical spectrum, in which the phenotype can vary widely, even in patients with a similar GAA genotype. The aim of this study was to describe phenotypic variation among siblings with non-classic Pompe disease in the Netherlands. We identified 22 families consisting of two or three siblings (50 patients: 42 adults and eight children). All carried the most common mutation c.-32-13T>G in combination with another pathogenic mutation. Siblings typically all had symptom onset either in childhood or in adulthood, however, there was a wide variation in age of symptom onset between siblings (median difference of nine years). Presenting symptoms were similar across siblings in 14 families and limb girdle weakness was most frequently reported. In certain families ptosis, bulbar weakness or scapular winging were present in all siblings. The majority of wheelchair and/or ventilator dependent patients had an ambulant or non-ventilated sibling; half of these less affected siblings had a longer disease duration. Gender, GAA activity and co-morbidity did not appear to explain differences in phenotype between siblings. Since the course of disease and its severity in some families varied to the same extent as seen in unrelated patients with an identical genotype, other factors like epigenetic and environmental effects are likely to influence the clinical presentation and disease course. Additional studies are needed to identify these factors, as possible prognostic factors for disease course and outcome on ERT of an individual patient.

P4.39 Enzyme replacement therapy during pregnancy and lactation in Pompe disease

Enzyme replacement therapy during pregnancy and lactation in Pompe disease J.M. de Vries , J.C. Brugma , L. Ozkan , M.A. Kroos , E.A.P. Steegers , A.J.J. Reuser , P.A. van Doorn , A.T. van der Ploeg f a Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Department of Neurology and Department of Pediatrics, Division of Metabolic Diseases, Rotterdam, Netherlands; b Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Hospital Pharmacy, Rotterdam, Netherlands; c Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Departement of Clinical Genetics, Rotterdam, Netherlands; d Erasmus MC University Medical Center, Department of Obstetrics and Gynaecology, Rotterdam, Netherlands; e Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Departement of Neurology, Rotterdam, Netherlands; f Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Departement of Pediatrics, Division of Metabolic Diseases, Rotterdam, Netherlands

P3.57 Clinical features, disease progression and prognostic factors of muscle weakness in adults with Pompe disease

35%. The auditory system assessment included vocal and pure tone audiometry, transient evoked oto-acoustic emissions (TEOAE), impedenziometry and auditory brainstem responses (ABR). A combined interpretation of those tests let us to define the origin of the hearing deficit (conductive, cochlear or retro-cochlear). Traumatic, inflammatory, iatrogenic and otosurgical causes have been excluded. From the clinical point of view, all but one, patients denied subjective hearing disturbances. On the other hand, audiological evaluation revealed that 12/20 patients (60%) had an hearing impairment. Among them, 5 pts showed a conductive hearing loss, while 7 pts had a sensorineural hearing deficit (5 pts with a cochlear dysfunction and 2 pts with a retro-cochlear pathology) and just one had a mixed pattern. Our observations revealed that, in this group of late onset Pompe patients, the auditory impairment is often present (60% of Pompe patients) Our data emphasize the importance of monitoring the auditory function since childhood in all patients with Pompe disease.