Genotype-Phenotype-Relationships in Inborn Errors of Metabolism

More than a century has passed since Archibald Garrod connected the excretion of homogentisic acid in normal and alkaptonuric members of families with an alternative course of metabolism and entitled his report specifically as a study in chemical individuality.1 This concept was later generalized in his book on “Inborn Factors of isease”.2 The tremendous work on the knowledgebase in human genetic disorders in “Mendelian Inheritance in Man” (MIM) by Victor A. McCusick published first in book form in twelve printed editions and various translations and subsequently in its online version OMIM, which is updated daily, is a great resource for the relationships between phenotype and genotype in teaching, research, applications and the clinic.3,4  

From the early days of the analysis of inborn errors of metabolism up to the present we are offering an ever increasing range of diagnostic metabolites for research and applications in order to support the establishment of genotype-phenotype relationships and to decrease the gap between the known and the available metabolites.

Selected Diagnostic Metabolites for Genotype-Phenotype-Relationships in Inborn Errors in Metabolism

Genotypes Phenotypes Metabolites
Chromosome Gene/Locus MIM No. Phenotype MIM No. Product No. Description
17q21.31 G6PC 613742  
Glycogen storage
disease
(von Gierke Disease)
232200 G7250 D-Glucose 6-
phosphate disodium
salt hydrate
13q32.3 PCCA 606054     Propionic
acidemia
232000         59464 Trisodium (2RS,3RS)-
2-methylcitrate
3q22.3 PCCB 606054       Propionic
acidemia
232050 59464 Trisodium (2RS,3RS)-
2-methylcitrate
21q22.3 CBS 613381 Homocystinuria
(CBS deficiency)
236200 H6010
69453
L-Homocystine
L-Homocysteine
2q37.3 D2HGDH 609186 D-2-Hydroxyglutaric
aciduria 1
600721 H8378 D-α-Hydroxyglutaric
acid disodium salt
15q26.1 IDH2 147650 D-2-Hydroxyglutaric
aciduria 1
613657 H8378 D-α-Hydroxyglutaric
acid disodium salt
14q21.3 L2HGDH 609584 L-2-Hydroxyglutaric
aciduria
236792 90790 L-α-Hydroxyglutaric
acid disodium salt

 

References

  1. A.E.Garrod, The incidence of alkaptonuria: a study in chemical individuality, Lancet 2,1616-1620 (1902).
  2. A.E.Garrod, The inborn factors in disease: an essay, Clarendon Press, Oxford, United Kingdom (1931).
  3. V.A.McKusick, A 60-year tale of spots, maps, and genes, Annual Review Genomics Human Genetics 7, 1–27 (2006).
  4. V.A.McKusick, Mendelian Inheritance in Man and Its Online Version OMIM, The American Journal of Human Genetics, 80, 588-604 (2007).

 

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