[Juvenile Pompe disease: retrospective clinical study].

Introduction: Pompe disease or glycogen storage disease type II is an autosomal recessive disorder due to acid maltase deficiency. It is a rare disease with a prevalence of 1/40.000 in the dutch and african-american populations and 1/46000 in the australian population. There are three forms of clinical presentation (infantile-onset, childhood-onset and adult-onset), although the disease presents as a continuum of clinical phenotypes. Enzyme replacement therapy is available in Portugal since 2006.

Materials And Methods: The clinical files of four patients (two sisters) were analyzed retrospectively.

Results: In all, disease presented in the second year of life and the time to diagnosis ranged from two to eleven years. At diagnosis, all presented myopathic features with a delay in motor skills achievement and two had myocardium hypertrophy. Clinical suspicion arose as the result of respiratory failure during infection in two patients. Plasma creatine kinase and aminotransferases levels were increased in all. All patients progressed to pulmonary restrictive syndrome with chronic respiratory failure. The diagnosis was based on reduced activity of acid maltase in fibroblasts: 0 to 1.5% of the lower normal value. Muscle biopsy, performed in three patients, showed lysosomal glycogen accumulation. A c.1064T > C mutation in exon 6 of GAA (glucosidase-alpha-acid) gene was found in all patients, in homozygosity in one. In the sisters, it was associated to c.1666A > G and c.2065G > A mutations in exons 12 and 15, respectively and in the youngest patient, to c.380G > T mutation in exon 2. All patients started enzyme replacement therapy as soon as it became available, with good tolerance. The youngest patient died. The surviving patients maintain ventilatory support measures and physiotherapy. The oldest patient is wheelchair ridden and her sister keeps independent walking. The youngest uses a walking aid.

Conclusions: Our cases are clinically included in the juvenile form of Pompe Disease. Pompe disease should be suspected in progressive myopathies at any age, especially those involving limb-girdle and respiratory muscles and in small infants with cardiomyopathy. High creatine kinase is a sensitive, although nonspecific, marker. Given the great variability of the genetic findings, demonstration of reduced activity of acid maltase (in leukocytes or other tissues) remains the diagnosis cornerstone of this rare disorder.