Pompe overview

Mutations of the gene coding for acid α-glucosidase is associated with a large spectrum of clinical symptoms, ranging from severe sickness characterized by hypertrophic cardiomyopathy and marked muscle weakness to a gradually progressing myopathy and respiratory insufficiency with adult onset. The term infantile onset incorporates those patients who display symptoms before ۱ year of age, who have an average life expectancy of less than one year due to severe cardiac hypertrophy and generalized skeletal muscle weakness. Infantile-onset Pompe disease (IOPD) presents in the first days to weeks of life, with symptoms of hypotonia, cardiomyopathy, and respiratory insufficiency. Patient with classic infantile PD usually come to attention during their first two months of life with marked muscular hypotonia together with a rapidly progressing muscular weakness. Poor feeding and failure to thrive may be early complaints, but cyanosis and attacks of dyspnea begin promptly, and there is rapid progression to intractable cardiac failure. Without treatment, death usually occurs before the age of ۲ years. The term late onset is utilized to describe those who develop symptoms any time after ۱ year of age or as late as the ۷th decade and can be misleading as it includes the childhood, juvenile, and adult onset groups, with respiratory insufficiency, impaired mobility and limb girdle weakness resulting to significant morbidity and early death. Children and adults with low to moderate GAA activity (۳-۳۰%) generally have a less rapid and more variable disease course. Unlike the infantile-onset acid maltase deficiency, cardiomegaly, hepatomegaly, and macroglossia are uncommon. Motor milestones may be delayed. Weakness is slowly progressive and involves proximal greater than distal muscles in the legs and arms. Children often have hypertrophy of the calf muscles, a waddling gait, and significant lumbar lordosis and demonstrate a Gower maneuver to arise from the floor. The natural history of late-onset (childhood, juvenile, and adult) Pompe disease without ERT is characterized by onset of symptoms after ۱ year of age, less severe to no cardiac involvement, slower progression, and significant heterogeneity of symptoms, with symptoms primarily related to progressive dysfunction of skeletal and respiratory muscles.