Inborn errors of metabolism as a cause of neurological disease in adults: an approach to investigation

In 1927 Archibald Garrod presented the Huxley Lecture at Charing Cross Hospital1 Out of this lecture emerged the concept of an “inborn error of metabolism” whereby an inherited defect may lead to the accumulation in cells or body fluids of a metabolite which in itself may predispose to disease. The disorders cited as examples were all adult onset disorders.

Today there are over 200 known inborn errors of metabolism; however, the vast majority of cases reported are of childhood onset (<16 years of age). In part this may reflect the fact that the paediatric forms of the disease are more severe and hence more easily recognisable. However, in some cases it may be due to a lack of awareness by physicians treating adults of the possibility of inborn errors of metabolism being a cause of disease. Certainly, current experience of inborn errors of metabolism leads us to think that, potentially, every disorder has a milder form with a later onset.

In an attempt to increase awareness of adult onset inborn errors of metabolism this article reviews the disorders which can present at or older than 16 years of age with CNS or neuromuscular disease. We have included disorders in which the patient may present with mild or “soft” signs before that age, which are likely to be overlooked or mistaken for other disorders. This is not intended to be an in depth review of each disorder but rather to be a practical guide to the initial diagnosis of these disorders for neurologists outside specialist centres for the investigation of inborn errors of metabolism.