Case Study

Maternally inherited diabetes and deafness with a variable presentation across three generations within a pedigree, South Africa

Herbert Makgopa, Tanja Kemp, Surita Meldau, Engela M. Honey, Bettina Chale-Matsau
African Journal of Laboratory Medicine | Vol 13, No 1 | a2384 | DOI: https://doi.org/10.4102/ajlm.v13i1.2384 | © 2024 Herbert Makgopa, Tanja Kemp, Surita Meldau, Engela M. Honey, Bettina Chale-Matsau | This work is licensed under CC Attribution 4.0
Submitted: 05 December 2023 | Published: 29 May 2024

About the author(s)

Herbert Makgopa, Department of Chemical Pathology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa; and, Department of Chemical Pathology, National Health Laboratory Service, Pretoria, South Africa
Tanja Kemp, Division of Endocrinology, Department of Internal Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
Surita Meldau, Division of Chemical Pathology, Department of Pathology, University of Cape Town, Cape Town, South Africa; and, Department of Chemical Pathology, National Health Laboratory Service, Cape Town, South Africa
Engela M. Honey, Division of Human Genetics, Department of Biochemistry, Genetics and Microbiology, University of Pretoria, Pretoria, South Africa
Bettina Chale-Matsau, Department of Chemical Pathology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa; and, Department of Chemical Pathology, National Health Laboratory Service, Pretoria, South Africa

Abstract

Introduction: Maternally inherited diabetes and deafness (MIDD) is caused by the m.3243A>G pathogenic variant in maternally inherited mitochondrial DNA. Diabetes is prevalent in our setting; however, MIDD is rarely diagnosed. This study, undertaken in Pretoria, South Africa, highlights the variable presentation of MIDD in different patients within the same family.

Case presentation: A 45-year-old man (proband) with hearing impairment was referred to the endocrine unit in July 2015 due to poor glycaemic control (HbA1c = 13%). His clinical and biochemical features were in keeping with MIDD. A genetic study of accessible maternal relatives was pursued. His mother had difficulty hearing and reportedly died from an unspecified cardiovascular cause. Two sisters with diabetes and deafness died of cardiac-related conditions. One nephew had diabetes (HbA1c = 7.7%), hearing loss and tested positive for m.3243A>G. A third sister tested positive for m3243A>G, but aside from bilateral mild hearing loss in higher frequencies, showed no other signs of target organ damage. Her daughter developed end-stage kidney failure necessitating a transplant, while her son had no biochemical abnormalities and was negative for m.3243A>G.

Management and outcome: A multidisciplinary team managed and screened for complications of the patient and his maternal relatives. Proband died prior to genetic testing.

Conclusion: Most MIDD patients initially present with symptoms of diabetes only, and it is probable that many cases remain undiagnosed. A high index of suspicion is necessary when encountering a family history of both diabetes and impaired hearing, and screening should be offered to the patient’s maternal relatives.

What the study adds: This study demonstrates the importance of proper assessment when evaluating a patient with diabetes and a family history of hearing loss.


Keywords

diabetes; mitochondrial DNA; maternally inherited diabetes and deafness; heteroplasmy; hearing loss.

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