[Inborn errors of metabolism as rare diseases with a specific global situation]. / Los errores congénitos del metabolismo como enfermedades raras con un planteamiento global específico.

So-called congenital metabolic diseases (CMD) are a consequence of biochemical alterations originating in the genes that result in the alteration of a protein. Depending on this protein's function - whether as an enzyme, a hormone, a receiver-transporter of a cellular membrane or forming part of a cellular organelle (lysosome, peroxysome) - different groups of diseases emerge, which cause the most outstanding characteristic of inborn errors of metabolism (IEM): their clinical heterogeneity. The majority of these diseases are autosomal recessive, with a limited number of asymptomatic carriers, but there are also those ruled by an autonomous, dominant character inheritance or linked to the X chromosome. Taken individually, CMDs are highly infrequent, but taken as a whole CMDs (of which over 500 have been described to date) can affect 1/500 of the newborn. A common characteristic of many CMDs is the possibility of dietary treatment and treatment with enzymatic replacement. For essentially didactic purposes the following groups should be considered: CMDs of the intermediary metabolism (whose types are intoxication and energy deficit), CMDs of cellular organelles, complex CMDs due to cycle alterations and others. A summary is presented of the clinical, diagnostic and therapeutic aspects of one disease of each type of those previously described: hyperphenylalaninemias, deficiencies of the mitochondrial oxidative phosphorilation (OXPHOS) and lysosomal storage diseases.

Los errores congénitos del metabolismo como enfermedades raras con un planteamiento global específico / Inborn errors of metabolism as rare diseases with a specific global situation

Las llamadas enfermedades congénitas del metabolismo(ECM) son consecuencia de alteraciones bioquímicasde origen génico que tienen como consecuencia la alteraciónde una proteína. Dependiendo de la función de estaproteína, ya sea como un enzima; como una hormona; comoun receptor-transportador de membrana celular; o formandoparte de una organela celular (lisosoma, peroxisoma)surgen diferentes grupos de enfermedades, lo cual originala característica más destacada de los errores innatos delmetabolismo (EIM) que es su gran heterogeneidad clínica.La mayoría de estas enfermedades son autosómico-recesivas,con un número limitado de portadores asintomáticos,pero también las hay regidas por una herencia de carácterautonómica dominante o ligada al cromosoma X. Uno a uno,realmente los ECM son muy poco frecuentes pero en suconjunto los ECM (de los cuales hay descritos en el momentoactual más de 500) pueden afectar al 1/500 recién nacidos.Una característica común a muchos ECM es la posibilidadde tratamiento dietético y el tratamiento con sustituciónenzimática.Desde el punto de vista práctico es útil considerar suclasificacion atendiendo al momento de inicio de los síntomasy a la forma de presentación de las manifestaciones clínicas.Desde esta perspectiva y con fines fundamentalmentedidácticos se deben considerar los siguientes grupos:ECM del metabolismo intermediario, (tipo intoxicación, ytipo déficit energético). Errores congénitos del metabolismode las organelas celulares, y EMCM complejos por alteraciónde ciclos y otros. Se presentan de forma resumidalos aspectos clínicos, diagnósticos y terapéuticos de unaenfermedad de cada tipo de las descritas anteriormente:hiperfenilalaninemias, deficiencias de la fosforilación oxidativamitocondrial (OXPHOS) y enfermedades lisosomales

So-called congenital metabolic diseases (CMD) are aconsequence of biochemical alterations originating in thegenes that result in the alteration of a protein. Dependingon this protein’s function - whether as an enzyme, a hormone,a receiver-transporter of a cellular membrane orforming part of a cellular organelle (lysosome, peroxysome)– different groups of diseases emerge, which cause the mostoutstanding characteristic of inborn errors of metabolism(IEM): their clinical heterogeneity. The majority of these diseasesare autosomal recessive, with a limited number ofasymptomatic carriers, but there are also those ruled by anautonomous, dominant character inheritance or linked tothe X chromosome. Taken individually, CMDs are highlyinfrequent, but taken as a whole CMDs (of which over 500have been described to date) can affect 1/500 of the newborn.A common characteristic of many CMDs is the possibilityof dietary treatment and treatment with enzymaticreplacement.For essentially didactic purposes the following groupsshould be considered: CMDs of the intermediary metabolism(whose types are intoxication and energy deficit),CMDs of cellular organelles, complex CMDs due to cyclealterations and others. A summary is presented of the clinical,diagnostic and therapeutic aspects of one disease ofeach type of those previously described: hyperphenylalaninemias,deficiencies of the mitochondrial oxidative phosphorilation(OXPHOS) and lysosomal storage diseases

Molecular analysis of hereditary hyperferritinemia-cataract syndrome in a large Basque family.

Hereditary hyperferritinemia-cataract syndrome is a genetic condition characterized by constitutively increased serum ferritin values in the absence of iron overload and by bilateral cataract. It has been demonstrated that mutations in the stem loop structure of the iron regulatory element (IRE) located in the 5'-untranslated region of the ferritin L-subunit gene (19q13.1) are responsible for the anomalous expression of this protein. Although not clearly explained, cataract formation seems secondary to the increased levels of ferritin in the lens. We analyzed a large Basque family in order to identify possible germline alterations of the iron regulatory element of the ferritin-L gene in affected individuals and first-degree relatives. All members of the family presented hyperferritinemia and cataract except a young child who had hyperferritinemia but did not present cataract. Sequence analysis permitted the identification of an A40-->G mutation in all members, including this child. This could demonstrate that cataract formation is a consequence of ferritin accumulation in the lens.