Ataxia in Neurometabolic Disorders

Abstract

Ataxia is a movement disorder that manifests during the execution of purposeful movements. It results from damage to the structures of the cerebellum and its connections or the posterior cords of the spinal cord. It should be noted that, in addition to occurring as part of many diseases, pediatric ataxia is a common symptom in neurometabolic diseases. To date, there are more than 150 inherited metabolic disorders that can manifest as ataxia in children. Neuroimaging studies (magnetic resonance imaging of the head and spinal cord) are essential in the diagnosis of ataxia, and genetic studies are performed when metabolic diseases are suspected. It is important to remember that most of these disorders are progressive if left untreated. Therefore, it is crucial to include neurometabolic disorders in the differential diagnosis of ataxia, so that an early diagnosis can be made. Initiating prompt treatment influences positive neurodevelopmental outcomes.

PNPT1 Spectrum Disorders: An Underrecognized and Complex Group of Neurometabolic Disorders

“…Instead, they usually result from missense variants and a lack evidence of genetic anticipation. Considering that it is a protein that is structurally and functionally related to the mitochondria, similar to other mitochondrial contexts, such as variants in nuclear genome genes, like MFN2, OPA1, OPA2, OPA10, and mitochondrial genomes, such as some forms of Leber Hereditary Optic Neuropathy [10][11][12]32], heterozygous forms of PNPT1 should be strongly considered during the investigation of patients with cerebellar ataxia or spastic ataxia associated with optic atrophy. It is highly recommended to conduct comprehensive genetic testing with NGS-based panels or Whole-Exome Sequencing (WES), especially in cases without an identifiable family history and a higher association with de novo variants.…”

“…Additionally, there is the rare group of spastic ataxias (SPAXs), mostly of autosomal recessive inheritance, with clinical manifestations appearing early in infancy or childhood onset and an association with different neuroradiological, systemic, and neuro-ophthalmic findings [7,8]. In addition, it is important to consider inherited neurometabolic disorders and primary mitochondrial diseases, especially those related to pathogenic variants in the nuclear genome [9][10][11][12].…”