Background: As little information is available on children with non-classic presentations of Pompe disease, we wished to gain knowledge of specific clinical characteristics and genotypes. We included all patients younger than 18 years, who had been evaluated at the Pompe Center in Rotterdam, the Netherlands, between 1975 and 2012, excluding those with the classic-infantile form. None were treated with enzyme replacement therapy at the time of evaluation. We collected information on first symptoms, diagnosis, use of a wheelchair and/or respirator, and enzyme and mutation analysis and assessed muscle strength, pulmonary function, and cardiac parameters. Results: Thirty-one patients participated. Median age at symptom onset was 2.6 years (range 0.5-13y) and at diagnosis 4.0 years. Most first problems were delayed motor development and problems related to limb-girdle weakness. Fatigue, persistent diarrhea and problems in raising the head in supine position were other first complaints. Ten patients were asymptomatic at time of diagnosis. Five of them developed symptoms before inclusion in this study. Over 50 % of all patients had low or absent reflexes, a myopathic face, and scoliosis; 29 % were underweight. Muscle strength of the neck flexors, hip extensors, hip flexors, and shoulder abductors were most frequently reduced. Pulmonary function was decreased in over 48 % of the patients; 2 patients had cardiac hypertrophy. Patients with mutations other than the c.-32-13T > G were overall more severely affected, while 18 out of the 21 patients (86 %) with the c.-32-13T > G/'null' genotype were male. Conclusions: Our study shows that Pompe disease can present with severe mobility and respiratory problems during childhood. Pompe disease should be considered in the differential diagnosis of children with less familiar signs such as disproportional weakness of the neck flexors, unexplained fatigue, persistent diarrhea and unexplained high CK/ASAT/ALAT. Disease presentation appears to be different from adult patients. The majority of affected children with GAA genotype c.-32-13T > G/'null' appeared to be male.

Childhood, Clinical spectrum, Genotype, Natural course, Pompe disease,
Orphanet journal of rare diseases
This work was funded by the European Commission 7th Framework Programme; grant id fp7/201678 - A European Consortium for Lysosomal Disorders (EUCLYD), This work was funded by the European Commission 7th Framework Programme; grant id fp7/304999 - Clinical trial of gene therapy for MPS VI - a severe lysosomal storage disorder (MEUSIX)
Department of Clinical Genetics

van Capelle, C.I, van der Meijden, J.C, van den Hout, J.M.P, Jaeken, J, Baethmann, M, Voit, T, … van der Ploeg, A.T. (2016). Childhood Pompe disease: Clinical spectrum and genotype in 31 patients. Orphanet journal of rare diseases, 11(1). doi:10.1186/s13023-016-0442-y