RESUMEN
We performed a retrospective study of all patients with methylmalonic acidemia diagnosed during the past 20 years. Only those patients who were nonresponsive to vitamin B12 in vivo and in vitro were included. The final study group consisted of 26 patients, of whom 16 had a neonatal (early) onset; in 10 patients the diagnosis was made after 2 months to 2.2 years (late onset). Of the early-onset patients, 14 (87%) died, with a mean survival time of 1.5 years (range, 10 days to 2.5 years), whereas four of the late-onset patients (40%) died (range, 1.2 to 15 years). At present, eight patients are alive; their mean age is 4.6 years (range, 1 to 10 years). In the early 1970s, treatment was based on the principles of treating patients with phenylketonuria: restricting natural protein intake and supplementing essential amino acids, vitamins, and trace elements. After about 1980, nasogastric tube feeding became a mainstay of the therapy, natural protein restriction became stricter, and the use of essential amino acid mixtures diminished. Carnitine was added to the therapy and, in later years, metronidazole. Since these changes were implemented, the number of episodes of metabolic decompensation and hospitalizations has decreased. Mean survival time of the patients, in particular those with early onset, has only slightly improved, partly because of psychosocial problems in many of these families. Almost all the patients, especially those with early onset, had some degree of neurologic impairment and mental retardation, and many patients were at less than 2 SD for weight or height or both. In contrast, the neurologic and mental status of the late-onset patients was frequently normal, and their weight and height were more often within normal limits. Our results show that the treatment of methylmalonic acidemia still poses considerable problems; despite intense medical efforts and familial stress, the prognosis for the early-onset patients is disappointing. The patients with late-onset disease, however, appear to have a fairly good prognosis with the present therapeutic approach. Liver transplantation or possibly genetic therapy might improve our results in the future.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/dietoterapia , Errores Innatos del Metabolismo de los Aminoácidos/tratamiento farmacológico , Proteínas en la Dieta/administración & dosificación , Alimentos Fortificados , Ácido Metilmalónico/sangre , Vitamina B 12/uso terapéutico , Factores de Edad , Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Errores Innatos del Metabolismo de los Aminoácidos/mortalidad , Preescolar , Terapia Combinada , Evaluación de la Discapacidad , Humanos , Lactante , Recién Nacido , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
We report an inborn error of the tricarboxylic acid cycle, alpha-ketoglutarate dehydrogenase deficiency, in three siblings with hypotonia, metabolic acidosis, and hyperlactatemia immediately after birth. Neurologic deterioration resulted in death at about 30 months of age. We propose low molar ratios of ketone bodies in plasma of neonates with congenital lactic acidosis as an indication of dysfunction of the tricarboxylic acid cycle.
Asunto(s)
Acidosis Láctica/etiología , Complejo Cetoglutarato Deshidrogenasa/deficiencia , Acidosis Láctica/congénito , Acidosis Láctica/genética , Humanos , Recién Nacido , Cuerpos Cetónicos/sangre , Lactatos/sangre , Ácido Láctico , Masculino , Piruvatos/sangre , Ácido Pirúvico , RecurrenciaRESUMEN
Hypermethioninemia and absolute methionine intolerance were observed in three siblings. These patients had several peculiar clinical features comprising failure to thrive, mental and motor retardation, facial dysmorphy with abnormal hair and teeth, and myocardiopathy. Hepatic S-adenosylhomocysteine hydrolase activity was decreased by 80% in the three children. These clinical and biochemical features differ from those of hypermethioninemias previously described, and thus represent a new form of inherited disorder of methionine metabolism. Whether S-adenosylhomocysteine hydrolase deficiency is primary or secondary to an unknown metabolic defect remains to be determined.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/genética , Hidrolasas/deficiencia , Metionina/sangre , Adenosilhomocisteinasa , Errores Innatos del Metabolismo de los Aminoácidos/dietoterapia , Insuficiencia de Crecimiento/genética , Femenino , Humanos , Recién Nacido , Discapacidad Intelectual/genética , Ictericia Neonatal/genética , Hígado/enzimología , Metionina/administración & dosificaciónAsunto(s)
Adipatos/orina , Carnitina/deficiencia , Ácido Graso Desaturasas/deficiencia , Malonatos/orina , Errores Innatos del Metabolismo/metabolismo , Muerte Súbita del Lactante/etiología , Acil-CoA Deshidrogenasa , Humanos , Lactante , Recién Nacido , Errores Innatos del Metabolismo/complicaciones , Errores Innatos del Metabolismo/diagnóstico , RiesgoRESUMEN
Seven infants in one kindred died: one was stillborn; the others, who were floppy at birth and were breast-fed, developed a disorder with the odor of sweaty feet and died in early infancy. In two further pregnancies, 3-hydroxvisovaleric, glutaric, and C6-C10-dicarboxylic acids were demonstrated in the mother's urine during the seventh month. Riboflavin therapy in the last trimester of pregnancy and a riboflavin-rich diet given the infants prevented this syndrome. The presence of abnormal erythrocyte glutathione-reductase activity in the mother while she excreted normal amounts of riboflavin in her urine indicates a probable disorder of riboflavin metabolism resulting in multiple acyl-CoA dehydrogenase deficiency.
Asunto(s)
Acil-CoA Deshidrogenasas/deficiencia , Complicaciones del Embarazo/metabolismo , Riboflavina/metabolismo , Adulto , Lactancia Materna , Femenino , Humanos , Recién Nacido , Masculino , Enfermedades Metabólicas/tratamiento farmacológico , Enfermedades Metabólicas/genética , Enfermedades Metabólicas/orina , Errores Innatos del Metabolismo/prevención & control , Errores Innatos del Metabolismo/orina , Odorantes , Linaje , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Riboflavina/uso terapéutico , SíndromeRESUMEN
The variations in blood ketone bodies, blood glucose, and insulin were studied in 19 normal and 14 hypoglycemic children, 4 months to 13 years of age, during a 24-hour fast. Except in four patients (two with hyperinsulinism and two with congenital defect in ketogenesis), a significant increase in blood ketone bodies was observed in both controls and patients. A progressive decrease in glucose concentrations was observed up to but not after 20 hours. A highly negative correlation between blood ketone bodies and blood glucose was found, with a large dispersion of blood ketone bodies, especially for those corresponding to the blood glucose between 45 and 65 mg/dl. This dispersion was consistently reduced in a homogenous age group of 4 to 6 years with similar glucose values. There was a positive correlation between age and blood glucose from hour 21 on, and an inverse relationship between age and blood ketone bodies from hour 15 on. The same high inverse relationship between age and blood ketone bodies was again observed when the variable of glucose concentration was factored out, demonstrating that the variation in blood ketone bodies is indeed related to age. These findings need to be taken into account in the interpretation of fasting blood ketone bodies, especially when used as an aid in the diagnosis of the various forms of childhood hypoglycemia, and of hypoketotic states.