6533b830fe1ef96bd1297986

RESEARCH PRODUCT

G.P.232

subject

description

Spinal muscular atrophy (SMA) and Pompe disease (PD) are common neuromuscular disorders during childhood causing progressive weakness of proximal muscles with gait disturbances, loss of ambulation and breathing difficulties. Whereas SMA is the result of a neurogenic atrophy caused by mutations in the SMN1 gene, PD is a lysosomal glycogen storage disease (type II) due to mutations of the GAA gene responsible for the enzyme activity of acid alpha-1,4-glucosidase. PD is treatable by enzyme replacement therapy, but in SMA there is no established curable therapy. We report on a child with genetically proven SMA type III and PD caused by mutations in the SMN1 and GAA genes. A 3 years old girl presented with mild muscular weakness, unsteady walking and running difficulties in our neuromuscular outpatient clinic. As her twin brother she acquired motoric milestones at normal ages. There were no visible fasciculations, but the deep tendon reflexes were absent. Cardiac as well as pulmonary function was normal. Creatine kinase was slightly elevated (384 U/l), but lactate and uric acid were normal. Genetic analysis of the SMN1 gene detected a homozygous deletion of exon 7 and 8. In addition, we found a reduced GAA activity in blood cells. Further genetic studies revealed compound heterozygous mutations in the GAA gene: c.-32-13T>G; c.236_246delCCACACAGTGC. Muscle biopsy showed the typical pattern of a neurogenic atrophy with only few vacuolated fibres. The glycogen mass in muscle was normal, although GAA activity was clearly reduced. On electron microscopy, there were frequent neurogenic abnormalities, but no indications of vacuolation of muscle fibres. This case report describes the rare event of a coincidence of SMA type III and Pompe disease. Although, at present, the clinical and morphological signs of SMA are obvious, the question arises whether enzyme replacement therapy may influence the clinical course in a beneficial manner.