A novel homozygous mutation at the GAA gene in Mexicans with early-onset Pompe disease.

Glycogen-storage disease type II, also named Pompe disease, is caused by the deficiency of the enzyme acid alpha-glucosidase, which originates lysosomal glycogen accumulation leading to progressive neuromuscular damage. Early-onset Pompe disease shows a debilitating and frequently fulminating course. To date, more than 300 mutations have been described; the majority of them are unique to each affected individual. Most early-onset phenotypes are associated with frameshift mutations leading to a truncated alpha-glucosidase protein with loss of function. Founder effects are responsible from many cases from few highprevalence world regions. Herein we described two apparently unrelated cases affected with classical early-onset Pompe disease, both pertaining to a small region from Central Mexico (the State of San Luis Potosí), the same novel homozygous frameshift mutation at gene GAA (c.1987delC) was demonstrated in both cases. This GAA gene deletion implies a change of glutamine to serine at codon 663, and a new reading frame that ends after 33 base pairs, which leads to the translation of a truncated protein. This report contributes to widen the knowledge on the effect of pathogenic mutations in Pompe disease. Here we postulate the existence of a founder effect.

Enfermedad de Pompe Infantil: A propósito del primer caso reportado en Panamá / Pompe Disease in Children: First case reported in Panama

La enfermedad de Pompe (EP) es una rara enfermedad hereditaria causada por la deficiencia de la enzima alfa glucosidasa ácida (AGA) encargada de degradar el glucógeno intralisososmal. Se considera una enfermedad de depósito y existe en dos formas: la infantil o de aparición temprana y la de inicio tardío con manifestaciones luego del del año de edad. La forma infantil es rápidamente progresiva, causando la muerte antes del primer año de vida si no hay intervención terapéutica oportuna y adecuada. A partir del desarrollo de la terapia de reemplazo enzimática (TRE) el diagnóstico temprano cobra mayor relevancia. Se presenta el caso de una paciente de 8 meses de edad con dificultad respiratoria, hipotonía, alteración del desarrollo y la alimentación. La exploración cardiológica demostró hallazgos de miocardiopatía. Los hallazgos clínicos orientan hacia Enfermedad de Pompe. Se realiza la prueba en papel filtro que reporta positiva para enfermedad de Pompe. Sin embargo, la paciente fallece el día 25 de hospitalización antes de iniciar la terapia con reemplazo enzimático. Es el primer caso reportado en nuestro medio.

Pompe disease is a rare hereditary disease caused by deficiency of the enzyme alpha glucosidase acid (AGA) responsible for degrading intralisosomal glycogen. It is considered a deposit disease and exists in two forms: infantile or early onset and late onset with manifestations after one year of age. The infantile form is rapidly progressive, causing death before the first year of life if there is no timely and adequate therapeutic intervention. From the development of enzyme replacement therapy (ERT), early diagnosis becomes more relevant. The case of an 8-month-old patient with respiratory distress, hypotonia, impaired development and diet is presented. Cardiological examination showed findings of cardiomyopathy. Clinical findings point to Pompe disease. The test is done on filter paper that reports positive for Pompe disease. However, the patient dies on the 25th day of hospitalization before starting enzyme replacement therapy. It is the first case reported in our environment.