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Journal of Inherited Metabolic Disease

, Volume 29, Issue 2–3, pp 261–274 | Cite as

Clinical approach to treatable inborn metabolic diseases: An introduction

  • J.-M. Saudubray
  • F. Sedel
  • J. H. Walter
SSIEM SYMPOSIUM 2005

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.

Keywords

Fabrydisease Inborn Error Porphyria Homocystinurias Maple Syrup Urine Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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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Copyright information

© SSIEM and Springer 2006

Authors and Affiliations

  1. 1.Centre de Référence des Maladies Héréditaires du Métabolisme, Hôpital Necker Enfants-MaladesUniversité René DescartesParis Cedex 15France
  2. 2.Fédération des Maladies du Système NerveuxHôpital Pitié-SalpétrièreParisFrance
  3. 3.Willink Biochemical Genetics UnitRoyal Manchester Children's HospitalManchesterUK

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