Hypoparathyroidism in Mitochondrial Disorders

  • Daniele Orsucci
  • Gabriele Siciliano
  • Michelangelo MancusoEmail author


Mitochondrial diseases are a group of disorders caused by impairment of the mitochondrial respiratory chain. The genetic defect can be located on mitochondrial or nuclear DNA. Phenotypes are polymorphous and may range from pure myopathy to multisystem disorders, with variable age at onset, severity, and progression.

Many physicians, including many general endocrinologists and pediatricians with no specific interest in metabolic disorders, do not have in-depth knowledge of these diseases because of their rarity and complexity. However, in fact they are one of the most common groups of genetic metabolic disorders. In consideration of the frequent multisystem involvement, a wide range of medical specialists (including endocrinologists, pediatricians, neurologists, internists, general practitioners, cardiologists, audiologists, ophthalmologists, etc.) may first encounter these patients. An acute “clinical awareness” about this diagnosis is needed in order to initiate the correct diagnostic workup.

Possible metabolic/endocrine disturbances in patients with mitochondrial disorders include (but are not limited to) diabetes mellitus, hypothyroidism, hypogonadism, short stature, lactic acidosis, and multiple lipomatosis. Rarely, mitochondrial diseases may present with hypoparathyroidism. In this chapter, after a general overview on the basic concepts of the “mitochondrial medicine,” we review mitochondrial hypoparathyroidism, which in most cases is due to sporadic large-scale rearrangements of mitochondrial DNA.


Hypoparathyroidism Mitochondrial diseases mtDNA Parathyroid Single deletion 


  1. 1.
    DiMauro S, Schon EA (2003) Mitochondrial respiratory-chain diseases. N Engl J Med 348(26):2656–2668. doi: 10.1056/NEJMra022567348/26/2656 [pii]CrossRefPubMedGoogle Scholar
  2. 2.
    Filosto M, Mancuso M (2007) Mitochondrial diseases: a nosological update. Acta Neurol Scand 115(4):211–221. doi: 10.1111/j.1600-0404.2006.00777.x, ANE777 [pii]CrossRefPubMedGoogle Scholar
  3. 3.
    Schaefer AM, McFarland R, Blakely EL, He L, Whittaker RG, Taylor RW, Chinnery PF, Turnbull DM (2008) Prevalence of mitochondrial DNA disease in adults. Ann Neurol 63(1):35–39. doi: 10.1002/ana.21217 CrossRefPubMedGoogle Scholar
  4. 4.
    Mancuso M, Orsucci D, Coppede F, Nesti C, Choub A, Siciliano G (2009) Diagnostic approach to mitochondrial disorders: the need for a reliable biomarker. Curr Mol Med 9(9):1095–1107. doi:CMM#03 [pii]CrossRefPubMedGoogle Scholar
  5. 5.
    Mancuso M, Orsucci D, Filosto M, Simoncini C, Siciliano G (2012) Drugs and mitochondrial diseases: 40 queries and answers. Expert Opin Pharmacother. doi: 10.1517/14656566.2012.657177 PubMedGoogle Scholar
  6. 6.
    DiMauro S, Tay S, Mancuso M (2004) Mitochondrial encephalomyopathies: diagnostic approach. Ann N Y Acad Sci 1011:217–231CrossRefPubMedGoogle Scholar
  7. 7.
    Kitano A, Nishiyama S, Miike T, Hattori S, Ohtani Y, Matsuda I (1986) Mitochondrial cytopathy with lactic acidosis, carnitine deficiency and DeToni-Fanconi-Debre syndrome. Brain Dev 8(3):289–295CrossRefPubMedGoogle Scholar
  8. 8.
    Zupanc ML, Moraes CT, Shanske S, Langman CB, Ciafaloni E, DiMauro S (1991) Deletion of mitochondrial DNA in patients with combined features of Kearns-Sayre and MELAS syndromes. Ann Neurol 29(6):680–683. doi: 10.1002/ana.410290619 CrossRefPubMedGoogle Scholar
  9. 9.
    Tulinius MH, Oldfors A, Holme E, Larsson NG, Houshmand M, Fahleson P, Sigstrom L, Kristiansson B (1995) Atypical presentation of multisystem disorders in two girls with mitochondrial DNA deletions. Eur J Pediatr 154(1):35–42CrossRefPubMedGoogle Scholar
  10. 10.
    Isotani H, Fukumoto Y, Kawamura H, Furukawa K, Ohsawa N, Goto Y, Nishino I, Nonaka I (1996) Hypoparathyroidism and insulin-dependent diabetes mellitus in a patient with Kearns-Sayre syndrome harbouring a mitochondrial DNA deletion. Clin Endocrinol (Oxf) 45(5):637–641CrossRefGoogle Scholar
  11. 11.
    Wilichowski E, Gruters A, Kruse K, Rating D, Beetz R, Korenke GC, Ernst BP, Christen HJ, Hanefeld F (1997) Hypoparathyroidism and deafness associated with pleioplasmic large scale rearrangements of the mitochondrial DNA: a clinical and molecular genetic study of four children with Kearns-Sayre syndrome. Pediatr Res 41(2):193–200. doi: 10.1203/00006450-199704001-01165 CrossRefPubMedGoogle Scholar
  12. 12.
    Shankar RR, Haider A, Garvey WT, Freidenberg GR (1997) Multiple endocrinopathies in an infant with fatal neurodegenerative disease. Am J Med Genet 69(3):271–279. doi: 10.1002/(SICI)1096-8628(19970331)69:3<271::AID-AJMG11>3.0.CO;2-O [pii]CrossRefPubMedGoogle Scholar
  13. 13.
    Seneca S, De Meirleir L, De Schepper J, Balduck N, Jochmans K, Liebaers I, Lissens W (1997) Pearson marrow pancreas syndrome: a molecular study and clinical management. Clin Genet 51(5):338–342CrossRefPubMedGoogle Scholar
  14. 14.
    Tengan CH, Kiyomoto BH, Rocha MS, Tavares VL, Gabbai AA, Moraes CT (1998) Mitochondrial encephalomyopathy and hypoparathyroidism associated with a duplication and a deletion of mitochondrial deoxyribonucleic acid. J Clin Endocrinol Metab 83(1):125–129. doi: 10.1210/jcem.83.1.4497 PubMedGoogle Scholar
  15. 15.
    Katsanos KH, Elisaf M, Bairaktari E, Tsianos EV (2001) Severe hypomagnesemia and hypoparathyroidism in Kearns-Sayre syndrome. Am J Nephrol 21(2):150–153. doi:46239 [pii] 46239CrossRefPubMedGoogle Scholar
  16. 16.
    Lee YS, Yap HK, Barshop BA, Rajalingam S, Loke KY (2001) Mitochondrial tubulopathy: the many faces of mitochondrial disorders. Pediatr Nephrol 16(9):710–712. doi: 10.1007/s0046710160710 CrossRefPubMedGoogle Scholar
  17. 17.
    Labarthe F, Benoist JF, Brivet M, Vianey-Saban C, Despert F, de Baulny HO (2006) Partial hypoparathyroidism associated with mitochondrial trifunctional protein deficiency. Eur J Pediatr 165(6):389–391. doi: 10.1007/s00431-005-0052-5 CrossRefPubMedGoogle Scholar
  18. 18.
    Cassandrini D, Savasta S, Bozzola M, Tessa A, Pedemonte M, Assereto S, Stringara S, Minetti C, Santorelli FM, Bruno C (2006) Mitochondrial DNA deletion in a child with mitochondrial encephalomyopathy, growth hormone deficiency, and hypoparathyroidism. J Child Neurol 21(11):983–985CrossRefPubMedGoogle Scholar
  19. 19.
    Mihai CM, Catrinoiu D, Toringhibel M, Stoicescu RM, Hancu A (2009) De Toni-Debre-Fanconi syndrome in a patient with Kearns-Sayre syndrome: a case report. J Med Case Rep 3:101. doi: 10.1186/1752-1947-3-101 CrossRefPubMedCentralPubMedGoogle Scholar
  20. 20.
    Chae JH, Lim BC, Cheong HI, Hwang YS, Kim KJ, Hwang H (2010) A single large-scale deletion of mtDNA in a child with recurrent encephalopathy and tubulopathy. J Neurol Sci 292(1–2):104–106. doi: 10.1016/j.jns.2010.02.006, S0022-510X(10)00063-8 [pii]CrossRefPubMedGoogle Scholar
  21. 21.
    Tzoufi M, Makis A, Chaliasos N, Nakou I, Siomou E, Tsatsoulis A, Zikou A, Argyropoulou M, Bonnefont JP, Siamopoulou A (2013) A rare case report of simultaneous presentation of myopathy, Addison’s disease, primary hypoparathyroidism, and Fanconi syndrome in a child diagnosed with Kearns-Sayre syndrome. Eur J Pediatr 172(4):557–561. doi: 10.1007/s00431-012-1798-1 CrossRefPubMedGoogle Scholar
  22. 22.
    Abramowicz MJ, Cochaux P, Cohen LH, Vamos E (1996) Pernicious anaemia and hypoparathyroidism in a patient with Kearns-Sayre syndrome with mitochondrial DNA duplication. J Inherit Metab Dis 19(2):109–111CrossRefPubMedGoogle Scholar
  23. 23.
    Papadimitriou A, Hadjigeorgiou GM, Divari R, Papagalanis N, Comi G, Bresolin N (1996) The influence of Coenzyme Q10 on total serum calcium concentration in two patients with Kearns-Sayre Syndrome and hypoparathyroidism. Neuromuscul Disord 6(1):49–53CrossRefPubMedGoogle Scholar
  24. 24.
    Hameed R, Raafat F, Ramani P, Gray G, Roper HP, Milford DV (2001) Mitochondrial cytopathy presenting with focal segmental glomerulosclerosis, hypoparathyroidism, sensorineural deafness, and progressive neurological disease. Postgrad Med J 77(910):523–526CrossRefPubMedCentralPubMedGoogle Scholar
  25. 25.
    Morten KJ, Cooper JM, Brown GK, Lake BD, Pike D, Poulton J (1993) A new point mutation associated with mitochondrial encephalomyopathy. Hum Mol Genet 2(12):2081–2087CrossRefPubMedGoogle Scholar
  26. 26.
    Shigemoto M, Yoshimasa Y, Yamamoto Y, Hayashi T, Suga J, Inoue G, Okamoto M, Jingami H, Tsuda K, Yamamoto T, Yagura T, Oishi M, Tsujii S, Kuzuya H, Nakao K (1998) Clinical manifestations due to a point mutation of the mitochondrial tRNAleu(UUR) gene in five families with diabetes mellitus. Intern Med 37(3):265–272CrossRefPubMedGoogle Scholar
  27. 27.
    Tanaka K, Takada Y, Matsunaka T, Yuyama S, Fujino S, Maguchi M, Yamashita S, Yuba I (2000) Diabetes mellitus, deafness, muscle weakness and hypocalcemia in a patient with an A3243G mutation of the mitochondrial DNA. Intern Med 39(3):249–252CrossRefPubMedGoogle Scholar
  28. 28.
    Dionisi-Vici C, Garavaglia B, Burlina AB, Bertini E, Saponara I, Sabetta G, Taroni F (1996) Hypoparathyroidism in mitochondrial trifunctional protein deficiency. J Pediatr 129(1):159–162. doi:S0022-3476(96)70206-8 [pii]CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2015

Authors and Affiliations

  • Daniele Orsucci
    • 1
  • Gabriele Siciliano
    • 1
  • Michelangelo Mancuso
    • 1
    Email author
  1. 1.Neurological ClinicUniversity of PisaPisaItaly

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