Neurometabolic disorders

Excerpt

Isolated mental retardation (MR), or intellectual disability of apparently unknown cause, has become one of the most important concerns in public health, affecting up to 3% of the paediatric population. Despite the numerous advances accomplished in brain investigations, mainly in neurophysiology, brain imaging, classical and molecular karyotyping and molecular testing, many patients with MR remain undiagnosed. The hope of getting a specific treatment or at least a prognosis and genetic counselling motivates the strong demands of patients and their families for a specific diagnosis to be reached as early as possible. In this context, inborn errors of metabolism (IEMs), a group of genetic disorders expanding rapidly, appear very attractive since many of them are easy to diagnose by plasma or urine investigations, have a well-understood pathophysiology, are amenable to treatment, and can be recognized early in pregnancy. However, in countries where phenylketonuria is detected by newborn screening, IEMs are rare causes of isolated MR. There is no international agreement about what type of metabolic tests should be applied to patients with unspecific MR and there are two opposite practices: physicians not familiar with IEMs risk missing a diagnosis and a life-saving treatment; and those too naive or too systematic in performing metabolic investigations in inappropriate situations. …