An overview of inborn errors of metabolism affecting the brain: from neurodevelopment to neurodegenerative disorders

Abstract

Inborn errors of metabolism (IEMs) are particularly frequent as diseases of the nervous system. In the pediatric neurologic presentations of IEMs neurodevelopment is constantly disturbed and in fact, as far as biochemistry is involved, any kind of monogenic disease can become an IEM. Clinical features are very diverse and may present as a neurodevelopmental disorder (antenatal or late-onset), as well as an intermittent, a fixed chronic, or a progressive and late-onset neurodegenerative disorder. This also occurs within the same disorder in which a continuum spectrum of severity is frequently observed. In general, the small molecule defects have screening metabolic markers and many are treatable. By contrast only a few complex molecules defects have metabolic markers and most of them are not treatable so far. Recent molecular techniques have considerably contributed in the description of many new diseases and unexpected phenotypes. This paper provides a comprehensive list of IEMs that affect neurodevelopment and may also present with neurodegeneration.

Proposal for a simplified classification of IMD based on a pathophysiological approach: A practical guide for clinicians

“…-This approach has been used for a long time in our clinical practice and has been partly exposed in classic pediatric 5 and metabolic textbooks [6][7][8] as well as recent review papers. 9,10 -This proposal is organized into categories in order to facilitate the diagnosis and treatment of patients with IMD. However, patients have disorders in complex, overlapping, non-categorical biologic systems.…”

Manganese Mapping Using a Fluorescent Mn2+ Sensor and Nanosynchrotron X-ray Fluorescence Reveals the Role of the Golgi Apparatus as a Manganese Storage Site

“…22 A set of Mn 2+ transporters which included SLC30A14, SLC39A14 and SLC39A8 were also identified. 19,[23][24][25][26] Further, between 2009 and 2016, multiple studies by Tuschl and co-workers showed that mutations in the transporters, SLC39A14 and SLC30A10, led to manganese induced Parkinsonism in young adults and children. 19,22,[27][28][29] The past two decades have been extremely prolific with studies on Mn,…”

Clinicopathological Relationships in an Aged Case of DOORS Syndrome With a p.Arg506X Mutation in the ATP6V1B2 Gene

“…There is an ongoing debate regarding whether neurodevelopmental alterations including intellectual disability and neurodegeneration, e.g., accompanied by cognitive decline, have a different pathological basis or share a common one that yields a continuum regarding symptom evolution ( 22 ). The latter hypothesis is strongly presumed in some lysosomal disorders, including NPC ( 22 ). This may also be the situation in the current case.…”