Identification of a single MPV17 nonsense-associated altered splice variant in 24 South African infants with mitochondrial neurohepatopathy.

MPV17-related mitochondrial neurohepatopathy is a rare genetic disorder worldwide. We report on a novel pathogenic variant in the MPV17 gene in 24 unrelated neurohepatopathic infants of non-consanguineous Black South African heritage. Exome sequencing identified homozygosity for a c.106C>T nonsense variant in exon 3 of the human MPV17 gene in 2 unrelated index patients. mRNA analysis revealed transcripts both with and without exon 3, indicating both reduced splice efficiency and premature termination as mechanisms for disease. Carrier frequency in this population was found to be 1 in 68 (95% CI; 1/122-1/38) with an estimated newborn incidence of 1 in 18 496 (95% CI; 1/59 536-1/5776). Affected infants all presented with infantile onset neurohepatopathy with none surviving beyond infancy. This description of a relatively common pathogenic variant underlying a previously uncharacterized severe neurohepatopathy in South Africa will engender increased awareness, earlier diagnosis and possibly improve outcome if preventative or specific therapeutic options can be found.

Fulminant hepatitis B virus (HBV) infection in an infant following mother-to-child transmission of an e-minus HBV mutant: Time to relook at HBV prophylaxis in South African infants.

The prevalence of hepatitis B virus (HBV) infection in pregnant women is high in South Africa (SA), yet prophylaxis to prevent mother-to-child transmission (MTCT) falls short of international recommendations. We describe a 10-week-old infant who developed fulminant hepatic failure following MTCT. The mother was hepatitis e-antibody positive and had a viral load of only 760 IU/mL. Genetic analysis of virus from mother and infant showed that both had the G1896A mutation in the preC/C gene, which truncates hepatitis e antigen (HBeAg) during translation, causing an HBeAg-negative phenotype. HBeAg attenuates antiviral immune responses, and its absence was probably responsible for the infant's fulminant hepatitis, due to an uncontrolled immune attack on infected liver cells. Pregnant women are not tested for HBV infection in SA and MTCT rates are unknown. Addition of a birth dose of vaccine, HBV screening of pregnant women and antiviral prophylaxis to positive mothers should be prioritised.

Relations of intimal-medial thickness among sites within the carotid artery as evaluated by B-mode ultrasound. ARIC Investigators. Atherosclerosis Risk in Communities.

BACKGROUND AND PURPOSE: B-mode ultrasound is a widely used technique for the clinical and epidemiological assessment of carotid atherosclerosis. This article describes the relation between arterial intimal-medial thickness (IMT) at different sites within the extracranial carotid artery. METHODS: IMT was measured by B-mode real-time ultrasound as an index of atherosclerotic involvement in the extracranial carotid arteries as part of the population-based Atherosclerosis Risk in Communities (ARIC) study. The relation between IMT at different sites was described by correlation coefficients and percentile regression techniques based on between 4034 and 9386 pairs of measurements (variation in sample size depending on the paired sites). RESULTS: Increased IMT at one site was associated with increased IMT at other sites. The correlation between right and left IMT at the same anatomic location in the carotid artery ranged from .34 to .49; the correlation at different anatomic locations in the carotid artery on the same side ranged from .25 to .43. The distribution of IMT, described by the percentiles of IMT at the inference site as a function of IMT at the index site, showed constricted percentiles of IMT at the inference site for small IMT at the index site and an increase in the spread of percentiles with increasing IMT. CONCLUSIONS: Although increased carotid IMT at one site is positively associated with thickened walls at other carotid sites, the ability to accurately predict wall thickness at a site given the wall thickness at other sites is modest. The general association between sites supports the systemic nature of atherosclerosis, while the lack of tight agreement between sites supports the focal nature of the atherosclerotic process.