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Neurology India
Medknow Publications on behalf of the Neurological Society of India
ISSN: 0028-3886 EISSN: 1998-4022
Vol. 52, Num. 4, 2004, pp. 512-513

Neurology India, Vol. 52, No. 4, October-December, 2004, pp. 512-513

Letter To Editor

Diagnosis of mitochondrial diseases: Clinical and histological study of sixty patients with ragged red fibers: Authors’ Reply

Nizam’s Institute of Medical Sciences, Hyderabad
Correspondence Address:Nizam’s Institute of Medical Sciences, Hyderabad,

Code Number: ni04174


We thank Dr. Finsterer for his interest in our study. The aim of our study was to find the usefulness of the diagnostic criteria proposed by Bernie et al[1] to diagnose mitochondrial diseases when the patients present to the clinician. The clinical characteristics present at the initial visit were considered while categorizing the patients into various clinical syndromes. We have taken the presence of ragged-red fibers (RRFs), > 2% in the skeletal muscle as one of the important criteria for the diagnosis as we have no facilities for studying defects in respiratory chain (RC) complex expression and molecular studies to identify nuclear or mtDNA mutation of probable pathogenicity. The following is the clarifications to the concerns raised by Dr Finsterer.

Presenting phenotypic syndromes was the indication for muscle biopsy in 26 (43%) patients. In the remaining 34 patients we considered the possibility of mitochondrial disease clinically as they had two of the three clinical criteria proposed by Bernie et al.[1]

We categorized the patients into various clinical syndromes based on the presenting clinical characteristics at the initial visit. In mitochondrial diseases RRFs can be demonstrated in the clinically uninvolved muscles. Like in many center we do EMG in the right vastus lateralis and use left vastus lateralis biopsy.

We agree that multisystem involvement is a feature in a significant proportion of patients. As mentioned above we considered the presenting clinical characteristics at the first visit for the analysis. This may probably be one limitation for the low frequency of some of the systemic manifestations. It is quite possible that the patients would have developed some of these features in the course of the illness.

Particular abnormality in mitochondrial DNA may cause characteristic cardiac change in mitochondrial diseases and clinical features of cardiac involvement vary according to the different subgroups of mitochondrial disease: Kearns-Sayre syndrome - AV conduction disturbances in Kearns-Sayre syndrome, asymmetrical septal hypertrophy progressing to dilated cardiac myopathy in MERRF, and symmetrical ventricular hypertrophy with or without abnormal wall motion in MELAS. Cardiac involvement is atypical in ocular myopathy.[2] This may explain the low frequency of cardiac involvement in our series. In our series of the 60 patients studied progressive external ophthalmoplegia was the presenting clinical syndrome in 26 (43%) patients. Lack of comprehensive cardiac workup might have also been a factor. ECG showed evidence of complete block in 3 patients and one of them had dilated cardiomyopathy. All the three patients had permanent pace maker implantation.

In mitochondrial myopathies the serum CK is almost always normal or only mildly elevated (less than 3 times the upper limit of normal.[3],[4] Rather normal serum CK in patients with significant weakness raises the possibility of mitochondrial dysfunction.[3],[4],[5] Electromyography (EMG) may be normal.[3],[4],[5]

The discrepancy between the mean age at onset, mean age at diagnosis and mean disease duration is probably related to wide age range. Of the 60 patients, 10 were in the pediatric age groups (one month to 15 years).


1.Bernier FP, Bonesh A, Dennett X, Chow CW, Cleary MA, Thorburn DR. Diagnostic criteria for respiratory chain disorders in adults and children. Neurology 2002;59:1406-11.  Back to cited text no. 1    
2.Anan R, Nakagawa M, Miyata M, Higuchi I, Nakao S, Suehara M, et al. Cardiac involvement in mitochondrial diseases: A study on 17 patients with documented mitrochondrial DNA defects. Circulation 1995;91:955-61.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Dimauro S, Moraes CT. Mitochondrial encephalomyopathyies. Arch Neurol 1993;50:1197-208.  Back to cited text no. 3  [PUBMED]  
4.Jackson MJ, Schaefer JA, Johnson MA, Morris AA, Turnbull DM, Bindoff LA. Presentation and clinical investigation of mitochondrial respiratory chain disease: A study of 51 patients. Brain 1995;118:339-57.  Back to cited text no. 4  [PUBMED]  
5.Nardin RA, Johns DR. Mitochondrial dysfunction and neuromuscular disease. Muscle Nerve 2001:24:170-91.  Back to cited text no. 5    

Copyright 2004 - Neurology India

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