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

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.

A Scoping Review Evaluating the Current State of Gut Microbiota Research in Africa.

The gut microbiota has emerged as a key human health and disease determinant. However, there is a significant knowledge gap regarding the composition, diversity, and function of the gut microbiota, specifically in the African population. This scoping review aims to examine the existing literature on gut microbiota research conducted in Africa, providing an overview of the current knowledge and identifying research gaps. A comprehensive search strategy was employed to identify relevant studies. Databases including MEDLINE (PubMed), African Index Medicus (AIM), CINAHL (EBSCOhost), Science Citation index (Web of Science), Embase (Ovid), Scopus (Elsevier), WHO International Clinical Trials Registry Platform (ICTRP), and Google Scholar were searched for relevant articles. Studies investigating the gut microbiota in African populations of all age groups were included. The initial screening included a total of 2136 articles, of which 154 were included in this scoping review. The current scoping review revealed a limited number of studies investigating diseases of public health significance in relation to the gut microbiota. Among these studies, HIV (14.3%), colorectal cancer (5.2%), and diabetes mellitus (3.9%) received the most attention. The top five countries that contributed to gut microbiota research were South Africa (16.2%), Malawi (10.4%), Egypt (9.7%), Kenya (7.1%), and Nigeria (6.5%). The high number (n = 66) of studies that did not study any specific disease in relation to the gut microbiota remains a gap that needs to be filled. This scoping review brings attention to the prevalent utilization of observational study types (38.3%) in the studies analysed and emphasizes the importance of conducting more experimental studies. Furthermore, the findings reflect the need for more disease-focused, comprehensive, and population-specific gut microbiota studies across diverse African regions and ethnic groups to better understand the factors shaping gut microbiota composition and its implications for health and disease. Such knowledge has the potential to inform targeted interventions and personalized approaches for improving health outcomes in African populations.

Neonatal presentation of a patient with Liddle syndrome, South Africa.

Introduction: Liddle syndrome is an autosomal dominantly inherited disorder usually arising from single mutations of the genes that encode for the alpha, beta and gamma epithelial sodium channel (ENaC) subunits. This leads to refractory hypertension, hypokalaemia, metabolic alkalosis, hyporeninaemia and hypoaldosteronism, through over-activation of the ENaC. Case presentation: We describe a 5-day old neonate who presented with severe hypernatraemic dehydration requiring admission to Steve Biko Academic Hospital in South Africa in 2012. Further evaluation revealed features in keeping with Liddle syndrome. Two compound heterozygous mutations located at different subunits encoding the ENaC were detected following genetic sequencing done in 2020. The severe clinical phenotype observed here could be attributed to the synergistic effect of these known pathological mutations, but may also indicate that one of the other variants detected has hitherto undocumented pathological effects. Management and outcome: This child's treatment course was complicated by poor adherence to therapy, requiring numerous admissions over the years. Adequate blood pressure control was achieved only after the addition of amiloride at the end of 2018, which raised the suspicion of an ENaC abnormality. Conclusion: To our knowledge, this is the first Liddle syndrome case where a combined effect from mutations resulted in severe disease. This highlights the importance of early recognition and management of this highly treatable genetic disease to prevent the grave sequelae associated with long-standing hypertension. Whole exome sequencing may assist in the detection of known mutations, but may also unveil new potentially pathological variants. What this study adds: This study highlights the importance of developing a high index of suspicion of tubulopathy such as Liddle syndrome for any child presenting with persistent hypertension associated with hypokalaemic metabolic alkalosis.

Impact of potassium test sample rejections on routine laboratory service, South Africa.

Background: Accurate potassium measurements are necessary for effective clinical management of hyperkalaemia. Pre-analytical factors may affect laboratory measurements, leading to erroneous results and inappropriate patient management and negatively impact the efficiency and finances of laboratories and hospitals. Objective: This study evaluated the impact of rejected potassium test requests on laboratory service. Methods: We conducted a retrospective descriptive study to assess potassium test data at a public laboratory in Pretoria, Gauteng, South Africa, using samples collected from an academic hospital, peripheral hospitals, and outpatient clinics between January 2018 to December 2018. We assessed the relationship between reasons for rejection and health facility type, as well as financial implications for the laboratory. Results: The potassium result rejection rate was 15.1% (29 806 samples), out of the 197 405 requests received. The most common reasons for rejection were old sample (> 1 day old) (41.4%; 12 348 rejections) and haemolysis (38.2%; 11 398 rejections). The most frequent reason for rejections at the central, academic hospital was haemolysis (42.0%), while old sample was the most common reason for rejection at peripheral hospitals (43.4%; 4119/9493 requests) and outpatient health facilities (57.2%; 7208/12 605 requests) (p = 0.022). The total cost of potassium sample rejection over the study period was substantial, given the resource constraints in this setting. Conclusion: Peripheral hospitals and outpatient departments accounted for the majority of rejected potassium testing results, possibly resulting from delays in transportation; causing substantial financial impact on the laboratory. Improved sample collection, handling, and expedited transportation are recommended. What this study adds: This study highlights the importance of appropriate sample collection and handling and the undesirable consequences of non-adherence to these pre-analytical considerations.

Hyperthyroidism in molar pregnancy: ß-HCG levels do not always reflect severity.

BACKGROUND: Molar pregnancy is a complication characterised by abnormal benign or malignant proliferation of trophoblastic cells resulting in markedly elevated ß-hCG (human chorionic gonadotrophin) levels, an established marker for the presence of the disease. Owing to the structural homology between ß-hCG and TSH, the raised ß-hCG can result in secondary hyperthyroidism. METHODS: Two patients aged 20 (Case 1) and 31 years (Case 2) presented to the emergency department within a few days of each other complaining of vaginal bleeding associated with abdominal pain. Ultrasound evaluation, ß-hCG and thyroid function tests were performed on both patients. RESULTS: Both had elevated ß-hCG levels and ultrasound evidence of molar pregnancy and were diagnosed with gestational trophoblastic disease (GTD) associated with hyperthyroidism based on thyroid function test results. Case 1 had lower ß-hCG levels and free T4 levels compared with Case 2 but clinical assessment of the former revealed severe illness and more complicated course with the development of a thyroid storm. Case 2 had ß-hCG levels almost double those of Case 1, yet was stable and her levels decreased much faster, reaching and maintaining undetectable levels. CONCLUSIONS: These cases demonstrate that the ß-hCG levels do not always correlate with disease severity and prognosis in patients with GTD.