Myoclonus in Pediatric Metabolic Diseases: Clinical Spectrum, Mechanisms, and Treatable Causes—A Systematic Review

TL;DR

This paper reviews how myoclonus, a sudden involuntary movement, is a symptom of metabolic diseases in children and highlights treatable causes.

Contribution

The paper systematically summarizes the clinical spectrum, mechanisms, and treatable causes of metabolic myoclonus in pediatric patients.

Findings

Myoclonus is associated with six categories of inherited metabolic disorders.

Conditions like GLUT1 deficiency and folate receptor α deficiency are treatable with dietary or pharmacological interventions.

Metabolic screening is recommended for unexplained myoclonus, especially with developmental delay or systemic issues.

Abstract

Background: Myoclonus, a sudden brief shock-like involuntary movement, represents a common yet under-recognized manifestation across many inherited metabolic disorders. Although its occurrence has been reported in case series and small cohorts, the overall spectrum, pathophysiological mechanisms, and therapeutic relevance of metabolic myoclonus have not been systematically summarized. Methods: A systematic search of PubMed was conducted for English-language publications from 2014 to 2025 using predefined MeSH terms related to myoclonus, movement disorders, and inborn errors of metabolism. Titles and abstracts were screened independently by three reviewers. After removal of duplicates, 27 articles were included, complemented by 65 additional references addressing individual disorders. Data were organized according to the International Classification of Inherited Metabolic Disorders (ICIMD). Results: Myoclonus was documented across six ICIMD categories, including intermediary metabolism, mitochondrial energy metabolism, lipid metabolism, disorders of complex molecules and organelles, cofactor and mineral metabolism, and metabolic cell signaling disorders. Clinical presentation ranged from isolated jerks to progressive myoclonic epilepsies. Several conditions—such as GLUT1 deficiency, cerebrotendinous xanthomatosis, and folate receptor α deficiency—are treatable through dietary or pharmacological interventions. Conclusions: Recognition of myoclonus as a presenting feature of inherited errors of metabolism (IEMs) is critical for timely diagnosis and treatment. Metabolic screening should be considered in all unexplained cases of myoclonus, particularly when accompanied by developmental delay or systemic abnormalities.

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