Inborn Errors of Metabolism

Inborn Errors of Metabolism

Introduction

The term inborn errors of metabolism was coined by Garrod in 1908 for four rare hereditary diseases; albinism, alkaptonuria, cysteinuria and pentosuria. Such diseases occur even during birth and thus are inherited. Inherited errors of metabolism lead to inherited diseases.

The metabolism of our body comprises two major balanced activities: anabolism (synthesis) and catabolism (degradation). Whether the metabolic changes are exergonic or endergonic, most of them have to be catalysed by enzymes. If one particular enzyme is deficient or absent then that leads to a block in the pathway of biochemical reactions leading to metabolic abnormalities which are present throughout the life and handed over to the progeny.

The absence or deficiency of an enzyme will cause an abnormal accumulation of the intermediate products of metabolism in the body and increased excretion in urine as such or their degradation products. Some of the intermediates could even be toxic.

For example, in the following reaction

R is the reactant, B, C and D are intermediates and P is the product and a, b, c and d are enzymes catalyzing various steps of the reactions. In this reaction pathway, if any one of the enzyme is deficient or absent, the previous intermediate accumulates and produces toxicity. It also affects the amount of product (P) formation which may be essential biologically and there by leads to pathological diseases.

An enzyme usually controls one step in a sequence of reactions. Beadle and Tatum put forth their theory of one gene one enzyme hypothesis which states that one gene controls the synthesis of a single enzyme. It is also known that enzymes are being proteins, whose synthesis is governed by the DNA and aberrations of the enzyme protein will be definitely brought about by mutations in the DNA. Thus, diseases due to absence or deficiency of enzymes are due to defective genes in DNA. Hence, these hereditary or congenital diseases cannot be cured. The defective gene may be present in the autosomal chromosomes or in the sex chromosomes.

Galactosemia, Von-Gierke’s disease, hemophilia, albinism, alkaptonuria and Tay-Sach’s disease are some of the important diseases due to inborn errors of metabolism.