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Mitochondrial disorders: a potentially under-recognized etiology of infantile spasms
Namrata S Shah1, Wendy G Mitchell, Richard G Boles
1Division of Neurology, Childrens Hospital Los Angeles, CA, USA.
Insights
Mitochondrial disorders are increasingly recognized as a cause of infantile spasms, particularly in cases with unclear origins. Metabolic testing in infants with infantile spasms often reveals signs of defective energy metabolism.
Area of Science:
- Pediatric Neurology
- Neurogenetics
- Metabolic Disorders
Background:
- Infantile spasms (IS) are a severe epilepsy syndrome in infants, often linked to underlying brain insults.
- The etiology of IS is diverse, ranging from identifiable causes to cryptogenic cases where the origin is unknown.
- Metabolic derangements are suspected contributors to IS, but their prevalence requires further investigation.
Purpose of the Study:
- To investigate the etiology of infantile spasms in an unselected group of infants.
- To assess the role of metabolic work-up, including mitochondrial DNA testing and body fluid metabolite analysis, in cryptogenic cases.
- To determine the prevalence of defective energy metabolism in infants with infantile spasms.
Main Methods:
- Retrospective review of 56 infants diagnosed with infantile spasms.
- Etiological assessment including history, examination, and metabolic investigations (plasma lactate/pyruvate, urine organic acids).
- Mitochondrial DNA testing for A3243G mutation in specific cases.
Main Results:
- Of 56 infants, 34 had a symptomatic etiology, 1 was idiopathic, and 21 were cryptogenic.
- Mitochondrial DNA testing identified the A3243G mutation in two monozygotic twins.
- Metabolic testing suggested defective energy metabolism in the affected twins and 11 of 15 other cryptogenic cases.
Conclusions:
- Mitochondrial disorders should be considered in the differential diagnosis of infantile spasms.
- Abnormal energy metabolism appears prevalent in cryptogenic infantile spasms, indicating it may be a common cause or consequence.
- Comprehensive metabolic work-up is crucial for identifying treatable metabolic causes of infantile spasms.
Abstract:
Infantile spasms represent an age-dependent response of the immature brain to a wide variety of insults. An unselected group of children with infantile spasms were reviewed to determine etiology; a metabolic work-up was undertaken if the etiology was unclear from history and examination (cryptogenic). Of the 56 infants, 34 had a recognizable etiology (symptomatic), 1 had normal development (idiopathic), and 21 had cryptogenic infantile spasms. Among the latter, results of plasma lactate and pyruvate or urine organic acids were available in 17. In 2 infants (monozygotic twins), mitochondrial DNA testing revealed the relatively common A3243G mitochondrial mutation. In these twins and 11 of the remaining 15, body fluid metabolite testing suggested possible defective energy metabolism. Our twins and previous reports suggest that mitochondrial disorders should be considered in the differential diagnosis of infantile spasms. Among our cases remaining cryptogenic, signs of abnormal energy metabolism were prevalent, suggesting that metabolic derangements may be common causes or secondary consequences of infantile spasms.