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Investigación metabólica

Congenital metabolic diseases are a large group of genetic diseases. Most occur as a result of replacing a single nucleotide (SNP) of one gene. This gene encodes an enzyme, which facilitates (stimulates) the conversion of a particular substance (substrate) in another product (intermediate). Most disorders occur as a result of accumulation of substances that are toxic or interfere with the normal function. The complaints also can occur as a result of the inability to synthesize one essential connections. Inborn errors of metabolism are now often referred to as congenital metabolic diseases or simply metabolic diseases (inborn error of metabolism).

Read more about metabolic diseases

Traditionally the inherited metabolic diseases were classified as disorders of carbohydrate metabolism, amino acid metabolism, organic acid metabolism and leading to diseases. The relevant tests such as amino acid analysis or organic acids analysis have a corresponding name. In recent decades, hundreds of new inherited disorders of metabolism and discovered and the categories are therefore extended (see below).

Because of the huge number of these diseases and the wide range of metabolic pathways that may be affected, almost any persistent complaint can have congenital metabolic disease as a possible cause, especially in childhood. Primary lactic acidosis, galactosemia and urea cycle-diseases occur with a frequency of 24 on the 10,000 births. This most other diseases are with one to three out of 100,000 births, less frequent.

To the complaints include lack of growth and development, weight loss, lack of development of genitalia, delayed or strong early puberty, seizures, encephalopathy, abnormal skin pigmentation, hair growth, dental defects, recurrent vomiting, diarrhea, abdominal pain, excessive urination, renal failure, dehydration, enlarged heart, hypertension, unusual facial features, hyperventilation, abnormal behavior and cramps.

This are the most important classes of congenital metabolic diseases, with some examples per class.

  • carbohydrate metabolism such as Pompe disease or glycogen storage disease.
  • Amino acid metabolism for example, Hartnup disease, phenylketonuria, maple syrup disease.
  • ureumcyclus defect (UCD) for example carbamoyl phosphate synthetase deficiency (CPS1D)
  • organic acid metabolism (OZS), for example, alkaptonuria, 2-hydroxyglutaric aciduria
  • disorders of oxidation of the fatty acids (covers many areas that overlap with)
  • Mitochondrial metabolism for example acylcoenzym-A dehydrogenase deficiency (ADD)
  • Porphyrin metabolism for example, acute intermittent porphyria, HPU


There are many possibilities for therapies for these diseases. Vitamins may in some cases affect a metabolic pathway such as thiamine supplementation in milk acid acidosis. In many metabolic diseases may also be sufficient to offer a diet where the corresponding amino acid is only in very low concentration present, or where another sugar is offered, such as mannose.

One can give intermediate metabolites whereby a certain substance is not produced, such as alpha-ketoglutaric acid in ammonia metabolism disturbances. In this case glutamine is produced and not urea or uric acid which causes gout.

One can block biosynthesis pathways with certain medicines or can give certain enzymes via a tablet in retard-shaping like acid-alpha-glucosidase in Pompe disease or DPP IV-enzyme  in gluten sensitivity.