(MDS) Mitochondrial Depletion Syndromes

They include approximately 15 different conditions, autosomal recessive mitochondrial disorders that might also be sporadic. 

Signs and symptoms usually are present since infancy with hypotonic infants and lactic acidosis and metabolic dysfunction.  

Symptoms include muscle weakness, chronic fatigue, exercise intolerance, gastrointestinal defects, and imbalance problems, sleep dysfunction, optic and/or hearing problems, learning problems, headaches, peripheral neuropathy and more severe but rare symptoms and disorders such as liver and kidney dysfunction. Encephalopathy and seizures are the most usual complications of neonatal age. In children or adults sings include muscular, endocrine, cardiac and neurologic manifestations such as migraines, cardiomyopathy, retinopathy, dementia, ataxia, diabetes, optic atrophy and ophthalmoplegia. 

Diagnosis could take place clinic examination, MRI, blood tests, molecular tests, and muscle biopsy. Unfortunately the prognosis is poor. 

There is no cure yet, as well as there is not for any other mitochondrial disorders. But symptoms are managed appropriately for each organ. Multidisciplinary team of doctors, physiotherapist, occupational therapist, psychologist and others should work together and must assess the patients every 3-6 months. Amino acids, antioxidants, vitamins are suggested and when problems involve only the liver, transplantation is successful. 

Useful links

  1. https://www.omim.org/entry/615471
  2. https://www.chop.edu/conditions-diseases/mitochondrial-depletion-syndrome#
  3. https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=35698

Support Groups 

  1. https://www.mitoaction.org/
  2. https://www.umdf.org/

References  

  1. Basel D. Mitochondrial DNA Depletion Syndromes. Clin Perinatol. 2020; 47 (1): 123-141.
  2. Goldstein A. The elusive magic pill: finding effective therapies for mitochondrial

disorders. Neurotherapeutics 2013; 10 (2): 320–8.

  1. Chinnery PF. Mitochondrial disease in adults: what’s old and what’s new? EMBO

Mol Med 2015; 7 (12): 1503–12.

  1.  El-Hattab AW, Scaglia F. Mitochondrial DNA depletion syndromes: review and updates

of genetic basis, manifestations, and therapeutic options. Neurotherapeutics. 2013; 10: 186–98.

  1. Tarnopolsky MA. The mitochondrial cocktail: rationale for combined nutraceutical

herapy in mitochondrial cytopathies. Adv Drug Deliv Rev 2008; 60 (13–14):

1561–7.

  1. Rahman J, Rahman S. Mitochondrial medicine in the omics era. Lancet 2018;

391 (10139): 2560–74.

  1. Kamatani N, Kushiyama A, Toyo-Oka L, et al. Treatment of two mitochondrial disease

patients with a combination of febuxostat and inosine that enhances cellular

ATP. J Hum Genet 2019; 64 (4): 351–3.

  1.  Bulst S, Holinski-Feder E, Payne B, et al. In vitro supplementation with deoxynucleoside

monophosphates rescues mitochondrial DNA depletion. Mol Genet

Metab 2012;1 07 (0): 95–103.

  1. Abadi A, Crane JD, Ogborn D, et al. Supplementation with a-lipoic acid, CoQ10,

and vitamin E augments running performance and mitochondrial function in female

mice. PLoS One 2013; 8 (4): e60722.

  1. Saito K, Kimura N, Oda N, et al. Pyruvate therapy for mitochondrial DNA depletion

syndrome. Biochim Biophys Acta 2012; 1820 (5): 632–6.

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