THESES
Mitochondriopathies: contribution to the study of mitochondrial DNA mutations (abstract)* * Tese de Doutorado, Faculdade de Medicina da Universidade de São Paulo (Área: Neurologia). Orientador: Milberto Scaff.
Mitocondriopatias: contribuição para o estudo de mutações do DNA mitocondrial (resumo)
Suely Kazue Nagahashi-Marie** ** Address: Estrada de Santa Cruz 1005, 06850-000 Itapecerica da Serra SP, Brasil.
Mitochondriopathies: contribution to the study of mitochondrial dna mutations (abstract). Thesis. São Paulo, 1996.
Studies were carried out on 28 patients with ophthalmoplegia and palpebral ptosis: 5 with Kearns-Sayre syndrome (KSS), 1 with incomplete KSS, and 22 with chronic progressive external ophthalmoplegia (CPEO). All were examined for presence of deletion/insertion in the mitochondrial DNA by the Southern blot method. The deletion was mapped by the PCR method in 3 cases of KSS. Supplementary exams, muscular biopsy, and neuroimage findings were analyzed in the light of results of research of mutation of the mitochondrial DNA.
All patients with KSS presented deletion of mitochondrial DNA. Besides deletion, insertion of 4.9 kb was observed in one case of KSS. Six of the 22 patients with CPEO (27%) presented mitochondrial DNA deletion.
Deletions of mitochondrial DNA were detected only in the DNA extracted from skeletal muscles, except in the case of incomplete KSS. In this case, the same deletion was detected in peripheral blood.
All cases of KSS were sporadic, and only one case among patients with CPEO with deletion of mitochondrial DNA was familial. Multiple deletions were not detected in this case.
SDH histochemical technique was the more sensitive method for demonstrating mitochondrial proliferation in skeletal muscle fibers in all cases with deletion in the mitochondrial DNA.
The percentage of fibers with COX deficiency was greater than that of positive SDH fibers in all cases with deletion of mitochondrial DNA, suggesting that enzymatic dysfunction preceded mitochondrial proliferation.
The extent of mitochondrial DNA deletion was not correlated to the number of COX fibers.
There was no correlation between the extent of deletion in mitochondrial DNA and the intensity of morphological alteration upon muscular biopsy, and the severity of clinical picture.
Similar extent of deletion in mitochondrial DNA was observed in KSS and CPEO, suggeting that the extent of the deletion was not a determinant factor in the tissue distribution of this mutation.
All patients with KSS studied by head magnetic resonance presented alterations. One patient with KSS had a cardiac pacemaker, and could not be submittted to this examination. None of the patients with CPEO presented similar alteration.
The lesions detected by head magnetic resonance were extremely stereotyped with distribution in bulbar, pontine, and mesencephalic tegmentum. There was compromise of the main viae of internuclear connection, of the structures of supranuclear regulation of the vertical conjugated movement, and of descending viae for control of the conjugated gaze, horizontal and vertical, and compromise of the nuclei of the III, IV, and VI cranial nerves. With this distribution, it can be said that alterations of the brainstem play a part in the genesis of ophthalmoplegia externa.
Key words: mitochondrial diseases, Kearns-Sayre syndrome, chronic progressive external ophthalmoplegia, mitochondrial mutations, head magnetic resonance image.
Publication Dates
-
Publication in this collection
10 Nov 2010 -
Date of issue
June 1997
