Clinico-radiological phenotyping and diagnostic pathways in childhood neurometabolic disorders—a practical introductory guide

Abstract

Inborn errors of metabolism (IEM) although individually rare, together constitute a significant proportion of childhood neurological disorders. Majority of these disorders occur due to deficiency of an enzyme in a specific metabolic pathway, leading to damage by accumulation of a toxic substrate or deficiency of an essential metabolite. Early diagnosis is crucial in many of these conditions to prevent or minimise brain damage. Whilst many of the neuroimaging features are nonspecific, certain disorders demonstrate specific patterns due to selective vulnerability of different structures to different insults. Along with clinical and biochemical profile, neuroimaging thus plays a pivotal role in differentiating metabolic disorders from other causes, in providing a differential diagnosis or suggesting a metabolic pathway derangement, and on occasion also helps make a specific diagnosis. This allows initiation of targeted metabolic and genetic work up and treatment. Familiarity with the clinical features, relevant biochemical features and neuroimaging findings of common metabolic disorders to facilitate a prompt diagnosis cannot thus be overemphasized. In this article, we describe the latest classification scheme, the clinical and biochemical clues and common radiological patterns. The diagnostic algorithm followed in daily practice after clinico-radiological phenotyping is alluded to and illustrated by clinical vignettes. Focused sections on neonatal metabolic disorders and mitochondrial disorders are also provided. The purpose of this article is to provide a brief overview and serve as a practical primer to clinical and radiological phenotypes and diagnostic aspects of IEM.