CLINICAL AND LABORATORY PROFILE OF CHILDREN WITH MITOCHONDRIAL DISORDERS

Abstract

Introduction: Mitochondrial disorders are a diverse group of inborn errors of metabolism caused by dysfunction of mitochondrial oxidative phosphorylation. They commonly present in children with non-specific neurological and systemic features, making early diagnosis challenging. This study aimed to characterize the clinical, biochemical, radiological, histopathological, and molecular profiles of pediatric mitochondrial disorders to improve early recognition and management.

Materials and Methods: A prospective observational study was conducted over one year at Indira Gandhi Institute of Child Health, Bengaluru, enrolling 67 children aged 1 month to 18 years with probable or definite mitochondrial disorders. Diagnosis was based on a composite scoring system integrating clinical, biochemical, radiological, and histopathological parameters. Investigations included blood tests, CSF analysis, tandem mass spectrometry, neuroimaging, muscle biopsy, and next-generation genetic sequencing where feasible.

Results: Leigh syndrome was the predominant phenotype (n=58). Neurological features such as seizures (78.2%), hypotonia (85.5%), dystonia (72.7%), and neuroregression (81.8%) were significantly more common in Leigh syndrome compared to other mitochondrial disorders. Elevated serum lactate was observed in 94.5% of Leigh syndrome cases. MRI revealed classic Leigh pattern lesions in 80% of affected patients. Genetic mutations were identified in all 17 cases where sequencing was performed, with a predominance of nuclear gene mutations. A high consanguinity rate (55.2%) was noted, correlating with the autosomal recessive inheritance pattern.

Conclusion: Pediatric mitochondrial disorders exhibit broad clinical heterogeneity, with Leigh syndrome being the most frequent presentation. A multimodal diagnostic approach combining clinical evaluation, biochemical testing, imaging, histopathology, and genetic analysis enhances diagnostic yield. Early suspicion, particularly in consanguineous populations, coupled with comprehensive evaluation, is crucial for timely intervention and genetic counseling.