Neurológia pre prax 5/2010
Glycogen storage disease type II (GSD II, Pompe disease). Current diagnostic and therapeutic options. Clinical case report
Glycogenosis type II (GSD II) is a lysosomal storage disorder caused by insufficient activity of acid α-glucosidase (acid maltase). This enzyme is responsible for the degradation of intralysosomal glycogen. Accumulation of glycogen in lysosomes leads to the cellular dysfunction and damage in many organs and tissues. GSD is inherited in autosomal recessive trait, the incidence is panethnic approximately 1 : 60 000 of live-born children, the gene for α-glucosidase is localised on chromosome 17 (17q23). We differentiate the classical infantile onset type with first symptoms within the first few months of life, with generalized muscle weakness and hypotonia (floppy baby), hepatomegaly, progressive cardiomyopathy and death in first two years and the late-onset form presentating anytime during childhood or adulthood with slow progression of muscle weakness of legs, arms, trunk and diaphragm, but without cardiac involvment. In biochemical assessment we find elevation of creatinkinase, AST (SGOT), ALT (SGPT), LDH, the glycide metabolismus is normal, in clinical test with muscle ischemia we observe normal elevation of lactate in venous blood. Electromyography is with typical pseudomyotonic changes but with normal nerve conduction velocity. In muscle biopsy we see increased amount of structural normal glycogen in lysosomes and also intracellular. Diagnosis of Pompe disease is confirmed by low or absent acid α-glucosidase activity in cultured skin fibroblasts, purified lymphocytes, leucocytes or muscle cells. In last year we can also use a non-invasive acarbose-based assay performed on dried blood-spots. Mutation analysis can help in final verification of Pompe diagnosis. Prenatal diagnosis is possible due to DNA analysis or enzymologic assay in amniocytes or chorion villi samples. The only effectual treatment is the enzyme replacement therapy (ERT). Myozyme (alglucosidase alfa) is purified recombinant enzyme administered beweekly in short intravenous infusion in recommended dosis 20 mg/kg. Other treatment options, used in lysosomals storage disorders, like haemopoetic stem cell transplantation, substrat inhibition therapy, chaperons or gene therapy, are not suitable for GSD II. Palliative care and symptomatic therapy like ventilation support and physical therapy can be effective in managing symptoms, but can not prevent the disease progression. The diet with low sugar for glycogenolysis stimulation and high protein intake are of questionable effect. In the case report we present our experience with ERT in 37-year old patient with confirmed GSD II diagnosis.
Keywords: glycogen storage disease type II, Pompe disease, cardiomyopathy, hypotonia, myopathy.
