Inborn Errors of Metabolism

Abstract

The inborn errors of metabolism are a heterogeneous group of conditions that result from the defective activity of an enzyme or enzymes important to the functioning of a cell. Such enzymes have roles in the synthesis, conversion or degradation of essential chemicals in the body's cells, tissues and fluids.

Keywords: intermediary metabolism; heterogeneity; metabolic complementation; lysosomal enzymes

Figure 1.

Effect of (a) a common subunit and (b) a common protector protein (PP). N, neuraminidase; B, β‐galactosidase.

Figure 2.

The biotin cycle, CoA, coenzyme A.

Figure 3.

Deranged tyrosine metabolism in hepatorenal tyrosinaemia. With deficiency of fumarylacetoacetate hydrolase, fumarylacetoacetic acid is converted to highly reactive succinylacetoacetic acid. During treatment with 2‐(nitro‐4‐trifluoromethylbenzoyl)‐1,3‐cyclohexanedione (NTBC), formation of fumarylacetoacetic acid is blocked. Tyrosine and p‐hydroxyphenylpyruvic acid accumulate behind the block and the toxic compounds are not formed.

Figure 4.

Cross‐correction of lysosomal enzymes in vitro.

(a) Coculture of cells from a patient with mucopolysaccharidosis (MPS) I (iduronidase deficiency) and cells from a patient with MPS II (iduronate sulfatase deficiency). Each cell has a single enzymatic defect and is able to transfer enzyme from an intact step in the hydrolysis pathway to neighbouring cells. The result is that both cells experience complementation in the hydrolysis pathway and lysosomal engorgement decreases.

(b) When cells from two different patients with MPS I are cultured together, iduronidase activity is missing in both cell lines. Iduronate sulfatase is produced and transferred, as in (a), but no complementation takes place.

close

References

Endres W (1998) Diet in phenylketonuria: how long? Policies under discussion. Annals of Nutrition and Metabolism 42: 63–67.

Garrod AE (1902) The incidence of alkaptonuria: a study in chemical individuality. Lancet ii: 1616–1620. [www.esp.org/foundations/genetics/classical/ag‐02.pdf].

Grabowski GA and Leslie ND (1999) Lysosomal storage disease. In: Hoffman R, Benz EJ, Shattil SJ et al. (eds) Hematology: Basic Principles and Practice, 3rd edn. Philadelphia: WB Saunders.

Holme E and Lindstedt S (1995) Diagnosis and management of tyrosinemia type I. Current Opinion in Pediatrics 7: 726–732.

Hymes J and Wolf B (1996) Biotinidase and its roles in biotin metabolism. Clinica Chimica Acta 255: 1–11.

Kelley RI (1998) Smith–Lemli–Opitz syndrome: mutations and metabolic morphogenesis. American Journal of Human Genetics 63: 322–326.

Rouse B, Azen C, Koch R et al. (1997) Maternal Phenylketonuria Collaborative Study (MPKUCS) offspring: facial anomalies, malformations, and early neurological sequelae. American Journal of Medical Genetics 69: 89–95.

Scriver CR (1998) Seminal Articles with Commentaries: A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants, by Robert Guthrie and Ada Susi. Pediatrics 1963; 32: 318–343. Pediatrics 102: 235–237.

Scriver CR, Beaudet AL, Sly WS and Valle D (eds) (1995) The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw‐Hill.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Leslie, Nancy D, and Grabowski, Gregory A(Apr 2001) Inborn Errors of Metabolism. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0002276]