Maternally inherited diabetes and deafness (MIDD) syndrome with m.3243A > G mutation associated with renal failure — a case report
, 3, 4, 2, 4, 5
Abstract
Maternally-inherited diabetes with deafness (MIDD) is a rare form of monogenic diabetes that results, in most cases, from an A-to-G transition at position 3243 of mitochondrial DNA (m.3243A>G). The clinical presentation of m.3243A>G mutation is variable, ranging from mild to severe phenotypes. Diabetes is often accompanied by sensorineural deafness, cardiomyopathy, neuromuscular, psychiatric disorders, macular dystrophy and renal failure (kidney manifestations in adults presenting with this mutation remain poorly defined).
The study presents a case of a 40-years-old woman with a history of bilateral sensorineural deafness, renal failure and diabetes that was diagnosed due to increasing muscle weakness during exercise. MIDD was diagnosed based on the clinical picture and the results of laboratory studies including genetic testing. As far as we know, glomerulopathy with incomplete distal renal tubular acidosis has never been described before as a cause of renal failure in MIDD patients.
Keywords: mitochondrial diabetessensorineural deafnessm.3243A>G mutationrenal failureincomplete distal renal tubular acidosis
References
- Ballinger SW, Shoffner JM, Hedaya EV, et al. Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion. Nat Genet. 1992; 1(1): 11–15.
- Pavlakis SG, Phillips PC, DiMauro S, et al. Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome. Ann Neurol. 1984; 16(4): 481–488.
- Chinnery P. Molecular pathology of MELAS and MERRF. The relationship between mutation load and clinical phenotypes. Brain. 1997; 120(10): 1713–1721.
- Jansen JJ, Maassen JA, van der Woude FJ, et al. Mutation in mitochondrial tRNA(Leu(UUR)) gene associated with progressive kidney disease. J Am Soc Nephrol. 1997; 8(7): 1118–1124.
- Takeshima T, Nakashima K. MIDD and MELAS: a clinical spectrum. Intern Med. 2005; 44(4): 276–277.
- Guéry B, Choukroun G, Noël LH. The spectrum of systemic involvement in adults presenting with renal lesion and mitochondrial tRNA(Leu) gene mutation. J Am Soc Nephrol. 2003; 14(8): 2099.
- Małecki M, Skupień J. Problems in differential diagnosis of diabetes types. Polish Archives of Internal Medicine. 2008; 118(7-8): 435–440.
- Gerbitz KD, Ouweland Jv, Maassen J, et al. Mitochondrial diabetes mellitus: a review. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1995; 1271(1): 253–260.
- Sue CM, Lipsett LJ, Crimmins DS, et al. Cochlear origin of hearing loss in MELAS syndrome. Ann Neurol. 1998; 43(3): 350–359.
- Yoneda M, Chomyn A, Martinuzzi A, et al. Marked replicative advantage of human mtDNA carrying a point mutation that causes the MELAS encephalomyopathy. Proc Natl Acad Sci U S A. 1992; 89(23): 11164–11168.
- Dinour D, Mini S, Polak-Charcon S, et al. Progressive nephropathy associated with mitochondrial tRNA gene mutation. Clin Nephrol. 2004; 62(2): 149–154.
- Löwik MM, Hol FA, Steenbergen EJ, et al. Mitochondrial tRNALeu(UUR) mutation in a patient with steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis. Nephrol Dial Transplant. 2005; 20(2): 336–341.
- Hotta O, Inoue CN, Miyabayashi S, et al. Clinical and pathologic features of focal segmental glomerulosclerosis with mitochondrial tRNALeu(UUR) gene mutation. Kidney Int. 2001; 59(4): 1236–1243.
- Szabolcs MJ, Seigle R, Shanske S, et al. Mitochondrial DNA deletion: a cause of chronic tubulointerstitial nephropathy. Kidney Int. 1994; 45(5): 1388–1396.
- Iwanicka-Pronicka K, Pollak A, Skórka A, et al. Postlingual Hearing Loss as a Mitochondrial 3243A>G Mutation Phenotype. PLoS ONE. 2012; 7(10): e44054.