Refining the phenotype of inborn errors of metabolism

Excerpt

In the early twentieth century, knowledge of metabolic disorders was confined to a handful of ‘orphan’ diseases. Phenylketonuria was the first of these inborn errors of metabolism to be unravelled and identified as being caused by an enzyme deficit, which then could be managed with a low protein diet. Since that time many of these conditions have subsequently been recognised as having a single-gene origin. However, as is common for conditions initially defined on the basis of a rigid clinical phenotype, ‘forme frustes’ are identified when definitive genetic testing becomes more widely available. As a result there is often a later expansion of the initial phenotype, underlining the importance of careful clinical description and directed ancillary investigations in the diagnosis of these disorders. …