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

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

JOURNAL=Frontiers in Neurology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1277944

DOI=10.3389/fneur.2023.1277944

ISSN=1664-2295

ABSTRACT=<sec id="sec1"><title>Introduction</title><p>Spinal muscular atrophy, Jokela type (SMAJ) is a rare autosomal dominantly hereditary form of spinal muscular atrophy caused by a point mutation c.197G&gt;T in <italic>CHCHD10</italic>. <italic>CHCHD10</italic> 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.</p></sec><sec id="sec2"><title>Methods</title><p>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.</p></sec><sec id="sec3"><title>Results</title><p>Adjusted for sex, age, and BMI, the SMAJ group had lower power output (<italic>p</italic> &lt; 0.001), maximal oxygen consumption (VO<sub>2</sub> max) (<italic>p</italic> &lt; 0.001), and mechanical efficiency (<italic>p</italic> &lt; 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 (<italic>p</italic> ≤ 0.001–0.030) and otherwise lactate in SMAJ was lower than controls and MM, in longitudinal analysis <italic>p</italic> = 0.018. In MM, the ventilatory equivalent for oxygen was higher (<italic>p</italic> = 0.040), and the fraction of end-tidal CO<sub>2</sub> lower in maximal exercise compared to healthy controls (<italic>p</italic> = 0.023) and subjects with SMAJ.</p></sec><sec id="sec4"><title>Conclusion</title><p>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.</p></sec>