High-Throughout Techniques Assessing the Molecular Diagnosis for Neurometabolic Disorders: A Comprehensive Review

Neurometabolic diseases associated with neurological manifestations are a group of heterogeneous genetic disorders that share the alteration in specific aspects of cellular metabolism, ultimately leading to the disease. Often first described by pediatricians, the more recently reported adult-onset forms have phenotypes considerably different, sometimes, from the pediatric ones and might mimic other more common adults neurological disorders. Adult-onset neurometabolic diseases are individually rare, heterogeneous and frequently show complex clinical presentations. These reasons, in addition to the myriad of specialized biochemical diagnostic tools available, account for a significant diagnostic delay and under-diagnosis. However, unlike many other neurogenetic diseases, a substantial part of neurometabolic diseases can be successfully treated, with both conservative and more recently approved innovative therapeutics. Early recognition and diagnosis of a treatable neurometabolic disease should have major impacts, supports the stabilization of the disease or even the regression of some signs and symptoms, halting unnecessary diagnostic investigations, and allowing for family screening and treatment of pre-symptomatic carriers. An overview of adult-onset neurometabolic diseases will be outlined, starting from important general considerations to phenotypical descriptions focusing on treatable diseases. A diagnostic approach for the adult neurologist will be developed to help decision making when suspecting a neurometabolic disease. Neurometabolic Syndromes (NMS) are rare, heterogeneous genetic disorders that primarily affect the central nervous system (CNS) due to defects in specific metabolic pathways. Accurate, early diagnosis is critically important for initiating disease-modifying therapies, such as enzyme replacement or gene therapy, before irreversible neurological damage occurs