Lowered oxidative capacity in spinal muscular atrophy, Jokela type; comparison with mitochondrial muscle disease

Nadja Ratia; Edouard Palu; Hanna Lantto; Emil Ylikallio; Ritva Luukkonen; Anu Suomalainen; Mari Auranen; Päivi Piirilä

doi:10.3389/fneur.2023.1277944

Lowered oxidative capacity in spinal muscular atrophy, Jokela type; comparison with mitochondrial muscle disease

Front Neurol. 2023 Nov 8:14:1277944. doi: 10.3389/fneur.2023.1277944. eCollection 2023.

Authors

Nadja Ratia^#¹, Edouard Palu², Hanna Lantto^#¹, Emil Ylikallio^#^{3

4}, Ritva Luukkonen⁵, Anu Suomalainen^#^{3

6

7}, Mari Auranen^#³, Päivi Piirilä^#¹

Affiliations

¹ Unit of Clinical Physiology, HUS Medical Diagnosis Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
² Unit of Neurophysiology, HUS Medical Diagnosis Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
³ Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁴ Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁵ Finnish Institute of Occupational Health, Helsinki, Finland.
⁶ Research Program of Stem Cells and Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁷ Neuroscience Center, HiLife, University of Helsinki, Helsinki, Finland.

^# Contributed equally.

Abstract

Introduction: Spinal muscular atrophy, Jokela type (SMAJ) is a rare autosomal dominantly hereditary form of spinal muscular atrophy caused by a point mutation c.197G>T in CHCHD10. CHCHD10 is known to be involved in the regulation of mitochondrial function even though patients with SMAJ do not present with multiorgan symptoms of mitochondrial disease. We aimed to characterize the cardiopulmonary oxidative capacity of subjects with SMAJ compared to healthy controls and patients with mitochondrial myopathy.

Methods: Eleven patients with genetically verified SMAJ, 26 subjects with mitochondrial myopathy (MM), and 28 healthy volunteers underwent a cardiopulmonary exercise test with lactate and ammonia sampling. The effect of the diagnosis group on the test results was analysed using a linear model.

Results: Adjusted for sex, age, and BMI, the SMAJ group had lower power output (p < 0.001), maximal oxygen consumption (VO₂ max) (p < 0.001), and mechanical efficiency (p < 0.001) compared to the healthy controls but like that in MM. In the SMAJ group and healthy controls, plasma lactate was lower than in MM measured at rest, light exercise, and 30 min after exercise (p ≤ 0.001-0.030) and otherwise lactate in SMAJ was lower than controls and MM, in longitudinal analysis p = 0.018. In MM, the ventilatory equivalent for oxygen was higher (p = 0.040), and the fraction of end-tidal CO₂ lower in maximal exercise compared to healthy controls (p = 0.023) and subjects with SMAJ.

Conclusion: In cardiopulmonary exercise test, subjects with SMAJ showed a similar decrease in power output and oxidative capacity as subjects with mitochondrial myopathy but did not exhibit findings typical of mitochondrial disease.

Keywords: cardiopulmonary exercise testing; lactate; mitochondrial myopathy; motoneuron disease; spinal muscular atrophy Jokela type (SMAJ).

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Helsinki University Central Hospital governmental subsidy for health sciences Y780021092, Y780020130, Y780022062, Y780022062, and Y780023040.