An Argentine male child died at 4.5 years of age of a lethal mitochondrial disease associated with a MELAS mutation and a Barth syndrome-like presentation. The child had severe failure to thrive from the early months and for approximately two years thereafter. In addition, the patient had severely delayed gross motor milestones, marked muscle weakness, and dilated cardiomyopathy that progressed to congestive heart failure. He also had persistently elevated urinary levels of 3-methylglutaconic and 2-ethylhydracrylic acids and low blood levels of cholesterol. Detailed histopathologic evaluation of the skeletal muscle biopsy showed high activity of succinate dehydrogenase, a generalized decrease of COX activity, and abundant ragged-red fibers. Electron microscopic studies revealed multiple mitochondrial abnormalities in lymphocytes and monocytes, in the striated muscle, and in the postmortem samples (muscle, heart, liver, and brain). Biochemical analysis showed a pronounced and constant lactic acidosis, and abnormal urinary organic acid excretion (unchanged in the fasting and postprandial states). In addition, in CSF there was a marked increase of lactate and beta-hydroxybutyrate (beta-HOB) and also a high systemic ratio beta-HOB/acetoacetate. Enzymatic assay of the respiratory chain in biopsied muscle showed 10% of complex I activity and 24% of complex IV activity compared with controls. Molecular studies of the mitochondrial genome revealed an A to G mutation at nucleotide pair 3243 in mitochondrial DNA, a well-known pathogenetic mutation (MELAS mutation) in all the patient's tissues and also in the blood specimens of the probands mother and sibs (4 of 5). The diagnosis of MELAS mutation was reinforced by the absence of an identifiable mutation in the X-linked G4.5 gene of the propositus. The present observation gives additional evidence of the variable clinical expression of mtDNA mutations in humans and demonstrates that all clinical variants deserve adequate investigation to establish a primary defect. It also suggests adding Barth-like syndrome to the list of phenotypes with the MELAS mutation.

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RESUMENLa forma infantil de la enfermedad de Pompe conduce al óbito antes del año de vida por miocardiopatía o insuficiencia ventilatoria. Presentamos la experiencia de siete años de terapia de reemplazo enzimático en un niño diagnosticado a los 7 días de vida; se trata del seguimiento más prolongado en el país. El tratamiento fue bien tolerado, sin reacciones adversas asociadas. Los parámetros ecocardiográficos y electrocardiográ-ficos se normalizaron progresivamente en el primer año y se mantuvieron estables. El niño logró rolar y sentarse sin sostén, pautas que se perdieron a partir del tercer año. Ingresó en respirador a los 16 meses. Se mantiene vivo con 7 años de edad, con debilidad muscular generalizada grave. El niño superó notablemente la edad promedio de sobrevida y de ingreso a respirador. Fue clara la mejoría cardíaca, pero el beneficio sobre el músculo esquelético fue limitado. Palabras clave: enfermedad de Pompe, terapia de reemplazo enzimático, alfa-glucosidasa ácida, Argentina, Myozyme ® . SUMMARYThe infantile form of Pompe disease drives children to death before the first year of life due to cardiomyopathy and respiratory insufficiency. We present the seven-year follow-up experience with enzyme replacement therapy on a child with Pompe disease, being the longest follow-up in the country. The treatment was well tolerated without adverse reactions. The echocardiographic and electrocardiographic parameters clearly improved during the first year and remain stable. Motor milestones (like rolling over or sitting down without support) were initially achieved, but, after the third year were getting lost. The average age of ventilator dependence was also delayed (16 months). The 7-year old patient remains alive with severe generalized muscle weakness. The child notably overcame the average age of survival and onset of ventilator dependence. Although the cardiovascular improvement was clear, enzyme replacement therapy efficacy on skeletal muscle was limited in this patient. La forma infantil de la enfermedad de Pompe se caracteriza por hipotonía, debilidad muscular y miocardiopatía, aunque también se aprecia dificultad para alimentarse, retraso motor, hepatomegalia y dificultad respiratoria. Generalmente, estos niños mueren antes del año de vida 3,4 por fallo cardiorrespiratorio. 5El mayor avance en el tratamiento de la enfermedad de Pompe fue el desarrollo de la terapia de reemplazo enzimático, que consiste en realizar infusiones periódicas de alfa-glucosidasa ácida humana recombinante.El objetivo del presente artículo es presentar la experiencia de siete años de seguimiento de un niño con enfermedad de Pompe infantil, en tratamiento con terapia de reemplazo enzimático. CASO CLÍNICOPrimer hijo de padres no cosanguíneos, nacido de término. A los 5 días presentó cianosis peribucal, palidez, hipotonía y bradicardia, por lo que ingresó a cuidados intensivos neonatales. El electrocardiograma presentó intervalo PR acortado y complejos QRS gigantes. El ecocardiograma mostró miocardiopatía hipertrófica no obstru...

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