Inborn Errors of Metabolism


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.



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