Inherited Metabolic Disorders Overview

Overview

Inherited metabolic disorders (IMD) are very difficult to diagnose. Affected patients can present at any age; symptoms vary depending on age of onset and severity of the biochemical defect. Completely different parts of the brain may be involved in less severely affected patients compared with more severely affected patients. The same enzyme may perform different functions, in different parts of the brain, as the person matures from infancy to childhood to adulthood. Clearly, patients will have different symptoms if different parts of the brain are involved.

Adding to the confusion, IMDs have been classified in many different ways: Biochemical characteristics, the biochemical pathway that is affected, the cellular organelle in which the affected protein or affected biochemical pathway is located, characteristics of clinical presentation, and the gene that is affected. None of these classifications have been very successful, and it is likely that classification by the biochemical pathways affected will, ultimately, be the most useful.

The imaging features of inherited metabolic disorders can be equally confusing, particularly if not approached methodically. The imaging appearances of many disorders overlap and often vary with the stage and the variant of the disease. Imaging is most helpful early in the course of the disease, when it can help to narrow the differential diagnosis and reduce the amount of testing needed. From a neuroimaging perspective, it is most useful to classify disorders based on the pattern of brain involvement on MR early in the course of the disease . This pattern can be supplemented by the use of metabolic data (obtained from proton MR spectroscopy), diffusion data (obtained from diffusion-weighted imaging), and, occasionally, magnetization transfer.