A Novel Mutation of the Gaa Gene in a Patient with Early-Onset Pompe Disease Lacking a Disease-Specific Pathology.

Pompe disease, also known as glycogen storage disease type II (GSDII) or maltase deficiency, is caused by the absence or deficiency of acid alpha-glucosidase (GAA), a lysosomal enzyme that is responsible for the cleavage of the a-1,4- and a-1,6- glycosidic bonds of glycogen to glucose. The deficiency of the enzyme leads to the accumulation of glycogen in the lysosomes in numerous tissues, but clinical symptoms are primarily due to the cardiac and skeletal muscles involvement. The disease is characterized by a wide variety of manifestations ranging from severe infantile-onset muscle weakness, hypotonia, and hypertrophic cardiomyopathy to a relatively mild slowly progressive skeletal muscle myopathy in adults (4).The prevalence of Pompe disease is estimated to vary between 1 in 40,000 and 1 in 600,000 people, depending on geographical and ethnic factors ( 1,5). It has an autosomal recessive inheritance and it is caused by more than 300 mutations that occur all across the gene coding for acid alpha-glucosidase (GAA) located at locus 17q25.2q25.3 (2). The residual activity of this enzyme is primarily determined by the severity of the pathogenic mutations in both GAA alleles and is likely controlled by unknown modifying factors. The mutations are randomly spread throughout the entire gene and are typically discrete. In general, a good correlation between the nature of the mutation, and the severity of the clinical presentation is observed (3).We herein report on a novel homozygous mutation of the acid a-glucosidase (GAA) gene with early-onset Pompe disease. A 4-month-old boy was referred to our hospital because of highly elevated serum levels of creatine kinase (CK) and transaminases. He was the first child born to young, healthy and presumably unrelated parents. The baby was born via an uncomplicated vaginal delivery, with a normal birth weight (3,400 g). He had never been admitted to the hospital because of lower respiratory tract infection. Motor development was delayed and head control was not reached. He was found to have a systolic murmur, grade III, with reinforcement at the tricuspid focus and an abdominal examination showed hepatomegaly. The echocardiogram showed a prominent biventricular hypertrophy, with an ejection fraction of 50%, and thus, severe hypertrophic cardiomyopathy was diagnosed. On the neurological examination he showed a weak cry, profound muscle weakness, while during traction of the patient from a supine position, head control was completely absent, and both legs remained in a position of profound hypotonia with decreased deep tendon reflexes. Laboratory values were as follows AST: 208 U/L, ALT: 152 U/L, CK: 496 U/L. These findings were felt to be compatible with glycogen storage disease type II (Pompe disease) and low leukocyte acid maltase activity 0.1 mmol/L/H (>3.3 mmol/L/H) confirmed the diagnosis. Genetic analysis showed a novel homozygous missense mutation in the GAA gene- c,1848C>A (p. …