Mitochondrial encephalomyopathies: clinical and neuroradiological spectrum

Mitochondrial encephalomyopathies are the most common neurometabolic disorders in childhood and are caused by disturbances of the oxidative phosphorylation pathway (Pyruvate Dehydrogenase, respiratory chain complexes I-V). Gene defects involve both, nuclear (nDNA) and mitochondrial (mtDNA) genes. According to the ubiquitous importance of ATP mitochondrial disorders show frequently a multisystem involvement. Organs with a high energy demand are predominantly affected: central and peripheral nervous system, muscle, heart, eye, inner ear, kidney, endocrinal glands. Elevated levels of lactate and alanine in any body fluid can be frequently detected.

In childhood, neurological symptoms are predominant. Mitochondrial syndromes (Kearns-Sayre syndrome, MELAS, MERRF) can be easily diagnosed by the typical clinical presentation and identification of mtDNA mutations. The majority of patients with mitochondrial encephalomyopathies, however, present with uncharacteristic features like psychomotor retardation, seizures, dementia, ataxia and pyramidal/extrapyramidal movement disorders, often precipitated by febrile infections. Diagnosis of a mitochondrial disorder in these cases is based on accumulated lactate and alanine in body fluids (esp. in CSF) and on the identification of biochemical deficiencies of one or more enzymes of the oxidative phosphorylation pathway in muscle tissue. MR tomography of the brain is an important diagnostic tool since characteristic findings are detectable in a substantial number of patients like symmetric alterations in basal ganglia and brain stem (Leigh syndrome) or in the white matter (leukodystrophy).

Therefore, diagnosis of mitochondrial encephalomyopathies in childhood is complex and comprise detailed clinical analysis, determination of organic and amino acids, neuroradiological studies and biochemical analysis of the energy metabolism in muscle biopsy specimens. Currently, only 15–20% of all childhood mitochondriopathies can be verified by the identification of a gene defect.