[Advances in the diagnosis and treatment of maple syrup urine disease: experience in Galicia (Spain)]. / Avances en el diagnóstico y tratamiento de la enfermedad de jarabe de arce, experiencia en Galicia.

INTRODUCTION: Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder caused by an inherited deficiency of branched chain alpha-ketoacid dehydrogenase activity. Accumulation of the amino acids leucine, isoleucine, valine and alloisoleucine and their metabolic products in cells and biological fluids results in severe brain dysfunction. PATIENTS AND METHODS: We present three cases of MSUD diagnosed in Galicia since 2000, the year in which the Extended Newborn Screening Program by tandem mass spectrometry was started in this region. One of the patients was diagnosed on the basis of early clinical presentation and the others by neonatal screening. Enzymatic and molecular studies confirmed two classic cases of MSUD and an intermediate variant. We describe the clinical and biochemical details at confirmation of diagnosis and the long-term outcome of the three patients. Throughout follow-up, all the patients maintained adequate leucine levels, which were near the normal range (mean levels: 220, 177 and 252 micromol/L, respectively). Several moderate metabolic decompensations were observed but leucine levels only occasionally exceeded 1000 micromol/L (one day in two patients). IQ tests were performed in all patients and scores were within the normal range. In view of our results, we believe the following measures are essential to improve the prognosis of MSUD: inclusion of this disease in Expanded Neonatal Screening Programs with early samples (at 2-3 days of life); aggressive treatment in the initial phase and during acute decompensations; strict metabolic control to prevent crises, monitoring of branched-chain amino acids (dried blood spot sample), and maintenance of long term plasma leucine levels below 300 micromol/L.

Avances en el diagnóstico y terapéutica de los niños con tirosinemia tipo I / Advances in the diagnosis and treatment of children with tyrosinemia type I

La tirosinemia Tipo I es un error genético del metabolismode la tirosina producido por un déficit deFumarilacetoacetato Hidrosilasa (FAH), último enzimaen la vía de degradación de la tirosina, que dalugar al acúmulo de metabolitos intermediarios maleily fumaril-acetoacetato produciendo toxicidad hepáticay renal, y el metabolito secundario succinilacetona,produciendo efectos sistémicos y locales.Se suele presentar como hepatopatía aguda o crónicay/o carcinoma hepatocelular, disfunción tubularrenal o manifestaciones neurológicas. Como alternativasterapéuticas en el momento actual destacarel tratamiento dietético, la terapia con NTBC (2-(2-Nitro-4-trifluorometilbenzoil) 1-3-ciclohexanodiona) yel trasplante hepático. Este último se reserva básicamentepara pacientes con mala respuesta alNTBC, riesgo de malignidad y/o mala calidad de vidacon las otras alternativas terapéuticas. Presentamos3 casos de pacientes que han recibido NTBCde forma precoz con muy buena respuesta clínica ybioquímica, como muestra del importante cambioque se ha producido en los últimos años en esta enfermedad,lo que conlleva a grandes mejoras tantoen la calidad de vida como en su pronóstico

Tyrosinemia type I is a inborn error of tyrosinemetabolism caused by a deficiency of fumarylacetoacetase(FAH), the last enzyme in the tyrosine catabolicpathway; as a result, the reactive compoundsmaleylacetoacetate and fumarylacetoacetate are formed,which are thought to be responsable for the liverand kidney injury, and the secondary metabolitesuccunylacetone, with regional and general injurys.Clinically the disorder is characterised by progressiveacute or chronic liver damage and/or hepatocellularcarcinoma, renal tubular dysfunction or neurologicalcrises. The current therapy includes dietaryrestriction, NTBC (2-(2-nitro-4-trifluoromethyl benzoyl)-1-3-cyclohexanedione) therapy and liver transplantation.The indications for liver transplantationinclude non-response to NTBC, risk of malignancyand poor quality of live related to the other therapies.Here we report 3 patients early managed with NTBCresulting in clinical and biochemical improvement, toshow the important changes in the managenent ofthe disease in the last years, with better quality of lifeand pronostic as a result