Summary
In view of the major improvements in treatment, it has become increasingly important that in order for first-line physicians not to miss a treatable disorder they should be able initiate a simple method of clinical screening, particularly in the emergency room. We present a simplified classification of treatable inborn errors of metabolism in three groups. Group 1 includes inborn errors of intermediary metabolism that give rise to an acute or chronic intoxication. It encompasses aminoacidopathies, organic acidurias, urea cycle disorders, sugar intolerances, metal disorders and porphyrias. Clinical expression can be acute or systemic or can involve a specific organ, and can strike in the neonatal period or later and intermittently from infancy to late adulthood. Most of these disorders are treatable and require the emergency removal of the toxin by special diets, extracorporeal procedures, cleansing drugs or vitamins. Group 2 includes inborn errors of intermediary metabolism that affect the cytoplasmic and mitochondrial energetic processes. Cytoplasmic defects encompass those affecting glycolysis, glycogenosis, gluconeogenesis, hyperinsulinisms, and creatine and pentose phosphate pathways; the latter are untreatable. Mitochondrial defects include respiratory chain disorders, and Krebs cycle and pyruvate oxidation defects, mostly untreatable, and disorders of fatty acid oxidation and ketone bodies that are treatable. Group 3 involves cellular organelles and includes lysosomal, peroxisomal, glycosylation, and cholesterol synthesis defects. Among these, some lysosomal disorders can be efficiently treated by enzyme replacement or substrate reduction therapies. Physicians can be faced with the possibility of a treatable inborn error in an emergency, either in the neonatal period or late in infancy to adulthood, or as chronic and progressive symptoms – general (failure to thrive), neurological, or specific for various organs or systems. These symptoms are summarized in four tables. In addition, an extensive list of medications used in the treatment of inborn errors is presented.
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Abbreviations
- 3PGD:
-
3-phosphoglycerate dehydrogenase
- BCAA:
-
branched-chain amino acid
- BRBGD:
-
biotin-responsive basal ganglia disease
- Cbl:
-
cobalamin
- CDG:
-
congenital disorder of glycosylation
- CPT I:
-
carnitine palmitoyltransferase type I
- CPT II:
-
carnitine palmitoyltransferase type II
- CTX:
-
cerebrotendinous xanthomatosis
- FAO:
-
fatty acid oxidation
- GTP:
-
guanosine triphosphate
- HELLP:
-
haemolysis, elevated liver function, low platelets
- HFI:
-
hereditary fructose intolerance
- IE:
-
inborn error
- IEM:
-
inborn error of metabolism
- LPI:
-
lysinuric protein intolerance
- HMG CoA:
-
3-hydroxy-3-methylglutaryl coenzyme A
- IVA:
-
isovaleric acidaemia
- LCHADD:
-
long-chain 3-hydroxy-acyl-CoA dehydrogenase deficiency
- MCD:
-
multiple carboxylase deficiency
- MMA:
-
methylmalonic acidaemia
- MSUD:
-
maple syrup urine disease
- MTHFR:
-
methylene tetrahydrofolate reductase
- OA:
-
organic aciduria
- OTC:
-
ornithine transcarbamylase
- PA:
-
propionic acidaemia
- PC:
-
pyruvate carboxylase
- PDH:
-
pyruvate dehydrogenase
- PKU:
-
phenylketonuria
- PNPO:
-
pyridox(am)ine-5'-phosphate oxidase
- PTP:
-
6-pyruvoyltetrahydropterin synthase
- TFP:
-
trifunctional protein
- TH:
-
tyrosine hydroxylase
- TL:
-
carnitine acyltranslocase
- UCD:
-
urea cycle disorders
- VLCADD:
-
very long-chain acyl-CoA dehydrogenase deficiency
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Communicating editor: Jean-Marie Saudubray
Competing interests: None declared
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Saudubray, JM., Sedel, F. & Walter, J.H. Clinical approach to treatable inborn metabolic diseases: An introduction. J Inherit Metab Dis 29, 261–274 (2006). https://doi.org/10.1007/s10545-006-0358-0
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DOI: https://doi.org/10.1007/s10545-006-0358-0