To the editor:

In a few cases, sideroblastic anemias seem to be associated with mitochondrial dysfunction.1  Indeed, mitochondrial dysfunction could result in apoptosis and ineffective hematopoeisis, and iron deposition within mitochondria of developing erythroblasts with ringed sideroblasts.1  We report here a patient with sideroblastic anemia and mitochondrial myopathy in whom long-term red blood cell transfusion therapy was stopped and improvement of muscle strength was observed under coenzyme Q10 therapy (CoQ10).

A 38-year-old man with no family medical history was diagnosed at 6 years of age with a presumptive diagnosis of aplastic anemia, refractory to corticosteroids, intravenous immunoglobulins, erythropoietin, and cyclosporine. Diagnosis of sideroblastic anemia was finally established at 16 years of age, and the patient required red blood cell transfusions every 3 weeks. When he was 29 years old, he complained of progressive development of cramps upon exertion and loss of strength. Hypogonadism was found, probably related to iron overload. Treatment with norethandrolone was given during one year, then danazol, with poor effectiveness. One year later, a bilateral ptosis, gracile aspect of muscle masses, and proximal muscle weakness were noted. Serum creatine phosphokinase level was within normal range, but aldolase level was increased at 12.4 U/L (normal, 0.0-7.6 U/L). Venous lactate level was 4.97mM (normal, 0.60-1.4mM). Serum ferritin level was 2642 μg/L (normal, < 350 μg/L) despite infusion of desferrioxamine. Electromyogram study was typical with a myogenic process. Muscle biopsy showed a typical pattern of mitochondrial myopathy with many ragged red fibers and total diffuse negative staining for cytochrome oxidase activity. Study of the respiratory chains showed a deficiency in complex I, III, and IV on both muscle and lymphocytes studies. Study of lymphocytes, muscle, and fibroblast mitochondrial DNA (mtDNA) was performed. No mtDNA point mutations could be identified using the Surveyor nuclease2  and large rearrangements and quantitative mtDNA anomalies have been excluded by long-range PCR (using a fragment of 15.5 kb) and quantitative PCR, respectively. However, the patient showed multiple mtDNA deletions in muscle by long-range PCR using a fragment of 8.3 kb.3  Measurement of CoQ10 concentration in muscle was not possible. Cardiac failure developed at the age of 31 years with an ejection fraction of left ventricule at 17%, requiring treatment with ramipril and carvedilol. At this time, CoQ10 was given at a daily dose of 400 mg after obtaining his informed consent. No more transfusions were required; within 3 months, hemoglobin concentration was greater than 10 g/dL, and for the past 7 years, the patient has been maintained on CoQ10. Gain of muscle volume, improvement of muscle strength, and normalization of cardiac function were also observed within 1 year.

The association of mitochondrial myopathy, lactic acidosis, and sideroblastic anemia has been reported rarely in relation with different mutations.4,5  Muscle and erythroid cells are affected, with progressive intolerance to exertion in childhood, then onset of sideroblastic anemia in adolescence with basal lactic acidemia and mitochondrial myopathy. In these studies, only supportive treatment is considered. Interestingly in our patient, dramatic reduction of red cell transfusion and improvement of muscle strength was observed after CoQ10 supplementation was given. Indeed, CoQ10 is a key component of the mitochondrial chain with antioxidant properties.6,7  It plays a main role in transporting electrons from complexes I and II to complex III in the mitochondrial respiratory chain. The efficacy of CoQ10 has been described in patients with neurodegenerative and neuromuscular disorders,7  but also in cardiac failure associated with iron overload,8  and in one patient with Pearson syndrome associating sideroblastic anemia and mitochondrial myopathy with a mitochondrial DNA deletion.9 

Authorship

Acknowledgments: We thank Nora Brahimi (Département de Génétique, Hôpital Necker, Paris, France) and Norma Beatriz Romero (Inserm UMR S974, Institut de Myologie, Hôpital Pitié-Salpétrière, Paris, France) for their technical help.

Contribution: All authors analyzed the data and contributed to writing the final version of the letter.

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Correspondence: Claude Bachmeyer, Service de Médecine Interne, CHU Tenon (AP-HP), 4 rue de la Chine, 75020 Paris, France; e-mail: claude.bachmeyer@tnn.aphp.fr.

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