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Ann Indian Acad Neurol
Ann Indian Acad Neurol
AIAN
Ann Indian Acad Neurol
Annals of Indian Academy of Neurology
0972-2327
1998-3549
Wolters Kluwer - Medknow India

AIAN-27-452
10.4103/aian.aian_76_24
Letters to the Editor
The Phenotypic Range of Mitochondrial Myopathies and Disorders is More Diverse Than Expected
Finsterer Josef
Department of Neurology, Neurology and Neurophysiology Center, Vienna, Austria
Address for correspondence: Prof. Josef Finsterer, Postfach 20, 1180 Vienna, Austria. E-mail: fifigs1@yahoo.de
Jul-Aug 2024
10 6 2024
27 4 452453
27 1 2024
01 5 2024
07 5 2024
Copyright: © 2024 Annals of Indian Academy of Neurology
2024
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pmcDear Editor,

We read with interest Menon et al.’s[1] article on a retrospective analysis of the hospital charts of 16 patients with mitochondrial myopathy diagnosed by muscle biopsy between 2005 and 2015. Seven patients had chronic progressive external ophthalmoplegia (CPEO), four had overlapping CPEO/limb girdle muscle weakness (LGMW), and five had isolated LGMW.[1] Extramuscular manifestations included seizures, diabetes, cardiomyopathy, and hypoacusis.[1] It was concluded that there are three subtypes of mitochondrial myopathy, 30% of mitochondrial myopathy patients have isolated LGMW, and these patients represent the severe end of the spectrum.[1] The article is excellent, but some points need discussion.

The first point is the small number of patients, which may account for a phenotypic spectrum of mitochondrial myopathies that does not represent the full range of mitochondrial myopathies reported.[1] In addition to the extraocular and proximal limb muscles, the facial muscles, pharyngeal muscles, axial muscles, distal limb muscles, pelvic floor muscles, and respiratory muscles may be involved.[2] Consideration of the full spectrum of mitochondrial myopathy is critical for assessing whether there are actually only three[1] or more subtypes of mitochondrial myopathy and for therapeutic management, which can vary significantly between these subtypes.

The small group size could also be responsible for the phenotypic spectrum of extramuscular manifestations being smaller than reported. The impairment of organs caused by a mitochondrial defect not only affects the brain, muscles, eyes, and ears, but also affects other organs such as the intestines, liver, pancreas, kidneys, blood cells, immune cells, skin, bones, and cartilage. The degree of multisystem involvement is also critical to the outcome of mitochondrial myopathy.

Furthermore, a genetically confirmed diagnosis would be desirable. However, biopsy is still important, especially in resource-limited settings, but has the disadvantage that it is often nonspecific and difficult to assess whether histologic and immunohistologic changes indicating a mitochondrial defect are primary or secondary. As genetic testing becomes cheaper and more easily accessible, it is likely that it will largely replace biopsy.

Another point is that respiratory chain dysfunction has only been documented by histochemistry and not by biochemistry. To determine whether a single or multiple respiratory chain complexes are impaired, it is imperative to perform biochemical studies of the muscle homogenate.

It remains unclear why shortness of breath was attributed to myopathy.[1] Involvement of respiratory muscles was not described in any of the 16 patients. A restrictive pattern was described in only one patient, and cardiomyopathy was present in another patient.[1] Did the remaining 14 patients with respiratory dysfunction suffer from heart failure, pulmonary embolism, asthma, or orthopedic disease? Were there any indications of respiratory muscle weakness during pulmonary function tests?

It was surprising to note that only one of 16 patients had a positive family history.[1] Since mitochondrial disorders are inherited through the maternal line in 75% of cases,[3] it can be assumed that more than a single patient had a positive family history for the disease.

Cerebrospinal fluid (CSF) lactate values of 35.8 mmol/l (patient 8) and 81 mmol/l (patient 9) are quite unusual. What were the reference limits for CSF lactate? Assuming that 2.1 mmol/l was the upper limit, these two patients must have had cerebral dysfunction.

To sum up, the phenotypic spectrum of mitochondrial myopathies and mitochondrial disorders, in general, is broader than expected. Diagnosis of mitochondrial disorder requires genetic confirmation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.
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REFERENCES

1. Menon D Nair SS Radhakrishnan N Saraf UU Nair M Clinical Spectrum of biopsy proven mitochondrial myopathy Neurol India 2023 71 1192 6 38174457
2. Kim GW Kim SM Sunwoo IN Chi JG Two cases of mitochondrial myopathy with predominant respiratory dysfunction Yonsei Med J 1991 32 184 9 1949922
3. Poulton J Finsterer J Yu-Wai-Man P Genetic counselling for maternally inherited mitochondrial disorders Mol Diagn Ther 2017 21 419 29 28536827
