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AimsMitochondrial diseases form one of the largest groups of inborn errors of metabolism. The birth prevalence is approximately 1/5000 in well-studied populations, but little has been reported from Sub-Saharan Africa. The aim of this study was to describe the genetics underlying mitochondrial disease in South Africa.MethodsAn audit was performed on all mitochondrial disease genetic testing performed in Cape Town, South Africa.ResultsOf 1614 samples tested for mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) variants in South Africa between 1994 and 2019, there were 155 (9.6 %) positive results. Pathogenic mtDNA variants accounted for 113 (73%)/155, from 96 families. Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes, 37 (33%)/113, Leber’s hereditary optic neuropathy, 26 (23%)/113, and single large mtDNA deletions, 22 (20%)/113, accounted for 76%. Thirty eight of 42 nDNA-positive results were homozygous for the MPV17 pathogenic variant c.106C>T (p.[Gln36Ter, Ser25Profs*49]) causing infantile neurohepatopathy, one of the largest homozygous groups reported in the literature. The other nDNA variants were in TAZ1, CPT2, BOLA3 and SERAC1. None were identified in SURF1, POLG or PDHA1.ConclusionsFinding a large group with a homozygous nuclear pathogenic variant emphasises the importance of looking for possible founder effects. The absence of other widely described pathogenic nDNA variants in this cohort may be due to reduced prevalence or insufficient testing. As advances in therapeutics develop, it is critical to develop diagnostic platforms on the African subcontinent so that population-specific genetic variations can be identified.

MPV17-related mitochondrial DNA depletion syndrome is a rare, lethal, autosomal recessive primary mitochondrial disorder characterised by infantile onset liver disease and neurological features, including hypotonia, developmental delay, failure to thrive and neuropathy. The aim of this study was to describe the presentation and clinical course of infants diagnosed with MPV17 neurohepatopathy, comparing those who were HIV-exposed on antiretroviral therapy (ART), including zidovudine and nevirapine to prevent perinatal HIV transmission, to infants who were not HIV exposed, using data from a multicentre MPV17 natural history study in South Africa. Between 2013 and 2024, 25 infants were diagnosed with MPV17 neurohepatopathy, 8 (32%) of whom were HIV-exposed and received ART at birth (7 received zidovudine), none were HIV-infected. Median birth weight was lower at 2.45 kg (IQR 2.28-2.71) in infants who were HIV-exposed compared to 2.86 kg (IQR 2.54-3.13) in HIV-unexposed infants (p = 0.02). Symptom onset occurred much earlier at a median of 3 days of age (IQR 0-10 days) in HIV-exposed infants compared to 60 days (IQR 14-90) in HIV-unexposed (p = 0.006). Infants exposed to HIV were more likely to develop liver failure (p = 0.02). Perinatal therapy with the nucleoside reverse transcriptase inhibitor zidovudine, a known mitochondrial toxin, was associated with accelerated clinical presentation and clinical course of MPV17 neurohepatopathy. Our findings suggest that less toxic antiretroviral therapy should be considered for perinatal HIV prophylaxis in HIV-exposed infants, particularly in our setting where there is a high carrier frequency of a single pathogenic MPV17 variant.

In third-world countries many children with epilepsy also suffer from malnutrition, anemia, liver disease, and immunosuppression. Doctors might have reservations about the use of anticonvulsants that could aggravate these disorders. The purpose of this study was to establish the prevalence of abnormal blood and serum values in children receiving carbamazepine or sodium valproate as monotherapy who attended a child neurology clinic serving a third-world community in Cape Town, South Africa. Blood samples were taken at routine follow-up visits from 104 children who had been on carbamazepine or sodium valproate monotherapy for at least 6 months. Hematology, serum chemistry, immunoglobulins, and anticonvulsant levels were measured by standard laboratory procedures. Very few subjects had any values outside accepted normal ranges. When clinically indicated and available, carbamazepine and sodium valproate can be prescribed for children from a third-world environment. Frequent blood and serum testing is not necessary in asymptomatic individuals. (J Child Neurol 1999;14:751-753).

In third-world countries many children with epilepsy also suffer from malnutrition, anemia, liver disease, and immunosuppression. Doctors might have reservations about the use of anticonvulsants that could aggravate these disorders. The purpose of this study was to establish the prevalence of abnormal blood and serum values in children receiving carbamazepine or sodium valproate as monotherapy who attended a child neurology clinic serving a third-world community in Cape Town, South Africa Blood samples were taken at routine follow-up visits from 104 children who had been on carbamazepine or sodium valproate monotherapy for at least 6 months. Hematology, serum chemistry, immunoglobulins, and anticonvulsant levels were measured by standard laboratory procedures. Very few subjects had any values outside accepted normal ranges. When clinically indicated and available, carbamazepine and sodium valproate can be prescribed for children from a third-world environment. Frequent blood and serum testing is not necessary in asymptomatic individuals.

Virtual reality (VR) is potentially effective in raising awareness of testicular diseases, promoting self-examination and early help-seeking among men. This paper presents an early economic evaluation exploring the potential cost-effectiveness of Enhancing Men's Awareness of Testicular diseases (E-MAT) , a VR interactive experience compared with E-MAT , electronic information, among male athletes Results from this economic evaluation will inform and support the design of a future randomized controlled trial (RCT). Results from an Irish feasibility trial (ClinicalTrials.gov identifier: NCT05146466) with 74 participants conducted in 2022 were employed. Benefits were measured in monetary units whereby the contingent valuation method was used to elicit participants' preferences through willingness-to-pay measures. A micro-cost analysis estimated the costs of the intervention and comparator and subsequent resource use. The costs and benefits of E-MAT and E-MAT were compared to determine the net benefit. Sensitivity analyses were also conducted. Base case analysis suggests participants were willing to pay €21.88 for E-MAT and €11.16 for E-MAT . The total cost of E-MAT was €104.09 and of E-MAT was €22.75 per participant. These estimates include capital and delivery costs, of which delivery costs were €25.02 and €22.40 for E-MAT and E-MAT , respectively. A negative net benefit indicates E-MAT was not cost-beneficial as delivered in the feasibility trial. Scenario analyses demonstrated reducing costs via delivery modifications increased the probability of E-MAT being considered cost-effective. The cost-benefit analysis was feasible, response rates were acceptable, and willingness-to-pay estimates were stable. Economic evaluations alongside feasibility trials enable early economic evaluations, informing the design and conduct of a future RCT. E-MAT had higher expected benefits (WTP) and costs than E-MAT , yielding a negative net benefit. Given the high cost of digital health interventions, investigating their cost-effectiveness early is important to inform and optimize resource allocation decisions. We present a series of scenarios to demonstrate how delivery modifications to reduce costs could improve the likelihood of E-MAT being considered cost-effective.

Background Virtual reality (VR) is potentially effective in raising awareness of testicular diseases, promoting self-examination and early help-seeking among men. This paper presents an early economic evaluation exploring the potential cost-effectiveness of Enhancing Men’s Awareness of Testicular diseases (E-MAT) VR , a VR interactive experience compared with E-MAT E , electronic information, among male athletes Results from this economic evaluation will inform and support the design of a future randomized controlled trial (RCT). Methods Results from an Irish feasibility trial (ClinicalTrials.gov identifier: NCT05146466) with 74 participants conducted in 2022 were employed. Benefits were measured in monetary units whereby the contingent valuation method was used to elicit participants’ preferences through willingness-to-pay measures. A micro-cost analysis estimated the costs of the intervention and comparator and subsequent resource use. The costs and benefits of E-MAT VR and E-MAT E were compared to determine the net benefit. Sensitivity analyses were also conducted. Results Base case analysis suggests participants were willing to pay €21.88 for E-MAT VR and €11.16 for E-MAT E . The total cost of E-MAT VR was €104.09 and of E-MAT E was €22.75 per participant. These estimates include capital and delivery costs, of which delivery costs were €25.02 and €22.40 for E-MAT VR and E-MAT E , respectively. A negative net benefit indicates E-MAT VR was not cost-beneficial as delivered in the feasibility trial. Scenario analyses demonstrated reducing costs via delivery modifications increased the probability of E-MAT VR being considered cost-effective. The cost–benefit analysis was feasible, response rates were acceptable, and willingness-to-pay estimates were stable. Conclusions Economic evaluations alongside feasibility trials enable early economic evaluations, informing the design and conduct of a future RCT. E-MAT VR had higher expected benefits (WTP) and costs than E-MAT E , yielding a negative net benefit. Given the high cost of digital health interventions, investigating their cost-effectiveness early is important to inform and optimize resource allocation decisions. We present a series of scenarios to demonstrate how delivery modifications to reduce costs could improve the likelihood of E-MAT VR being considered cost-effective.