Mitochondrial encephalomyopathies in childhood. I. Biochemical and morphologic investigations
M H Tulinius1, E Holme, B Kristiansson
1Department of Pediatrics, University of Göteborg, Ostra Hospital, Sweden.
Insights
Mitochondrial disorders are a key cause of pediatric central nervous system and neuromuscular diseases. Investigations involving muscle biopsies identified these conditions in children with hyperlactatemia.
Area of Science:
- Biochemistry
- Neurology
- Genetics
Background:
- Mitochondrial disorders present with diverse neurological and neuromuscular symptoms.
- Hyperlactatemia is a common indicator of mitochondrial dysfunction in children.
Purpose of the Study:
- To identify and characterize mitochondrial disorders in children with neurological or neuromuscular disease and hyperlactatemia.
- To establish diagnostic criteria for pediatric mitochondrial diseases.
Main Methods:
- Biochemical and morphological analysis of quadriceps muscle biopsies.
- Oximetric and spectrophotometric assessment of respiratory chain function.
- Mitochondrial DNA analysis for mutations and deletions.
Main Results:
- Twenty out of 50 children were diagnosed with mitochondrial disorders.
- Diagnostic criteria included abnormal respiratory chain function, enzyme deficiencies, and mitochondrial DNA abnormalities.
- Ten children had inconclusive results, neither confirming nor excluding mitochondrial disease.
Conclusions:
- Mitochondrial disorders are a significant cause of central nervous system and neuromuscular disease in children presenting with hyperlactatemia.
- Combined biochemical and morphological investigations are crucial for accurate diagnosis.
Abstract:
During a 4-year period (1984 to 1988), 50 children referred with manifestations of central nervous system or neuromuscular disease combined with hyperlactatemia were subjected to investigations that aimed to identify and characterize children with mitochondrial disorders. Biochemical and morphologic investigations of quadriceps muscle biopsy tissue were done, including oximetric and spectrophotometric analysis of the respiratory chain function, enzyme histochemistry, electron microscopy, and analysis of mitochondrial DNA. A diagnosis of mitochondrial disease was based on the presence of at least two of five criteria: (1) abnormal results of oximetry, (2) abnormal results of spectrophotometry, (3) enzyme histochemical evidence of cytochrome x oxidase deficiency, (4) deletions or point mutations of mitochondrial DNA, and (5) abundant ultrastructurally abnormal mitochondria. With the combined biochemical and morphologic investigation, 20 of the children were found to have mitochondrial disorders. In an additional 10 children a mitochondrial disorder was neither excluded nor verified. Mitochondrial disorders are thus an important cause of central nervous system and neuromuscular disease in children with hyperlactatemia.
