Hereditary angio-oedema in the Western Cape Province, South Africa

Background. Hereditary angio-oedema (HAE) is an autosomal dominant condition caused by a deficiency in the C1-esterase inhibitor protein, resulting in increased bradykinin release. It presents clinically with recurrent attacks of angio-oedema, commonly affecting the limbs, face, upper airway and gastrointestinal tract. Little is known about this condition in sub-Saharan Africa.Objectives. To analyse and report on the clinical presentation and treatment of patients with HAE in the Western Cape Province, South Africa.Methods. A retrospective analysis was conducted on a series of 60 cases of HAE seen between 2010 and 2015 at the Allergy Diagnostic and Clinical Research Unit, University of Cape Town Lung Institute, and the Allergy Clinic at Groote Schuur Hospital, Cape Town. The findings in 43 cases of type 1 HAE are described.Parameters assessed included age, gender, age of diagnosis, duration of illness, family history, identifiable triggers, average duration of attack, number of attacks per year and type of attack.Results. A total of 43 patients were included in this study. Of these, 65.1% (28/43) were female. The median age at diagnosis was 20 years (interquartile range (IQR) 10 - 27) and the median duration of illness 10.5 years (IQR 6 - 22). Of the patients, 62.8% (27/43), 32.6% (14/43) and 4.7% (2/43) were of mixed ancestry, white and black African, respectively; 51.2% (22/43) were index cases, with the remaining 48.8% (21/43) diagnoses via family member screening, 12 families making up the majority of the cohort. The mean (standard deviation) duration of an acute attack was 49 (25.8) hours, and 64.3% (27/42), 71.4% (30/42), 14.3% (6/42) and 88.1% (37/42) of patients experienced facial or upper airway, abdominal, external genitalia and limb attacks, respectively.Danazol for long-term prophylaxis was used in 21 patients, while C1-inhibitor concentrate (Berinert) was accessed for short-term prophylaxis in only four patients. Acute life-threating attacks were treated with fresh frozen plasma in 11 patients, and only four accessed icatibant. The mortality rate for the period 2010 - 2015 was 4.5% (2/43). The prevalence of HAE in the Western Cape was estimated to be 1:140 000.Conclusions.HAE occurs in South Africans of all ethnicities, and life-threatening attacks occur in almost two-thirds of patients. Despite limited therapeutic options and very limited access to gold-standard therapies available in the developed world, our mortality rate is very low, with both the deaths related to inability to access emergency treatment rapidly

Déterminisme génétique de l'anosmie : Cas des populations Hadjaraï au Tchad

Introduction :L'anosmie a des causes diverses. Cette affection a été observée chez les «Hadjaraï», originaires de la région du Guéra au centre du Tchad. Le but de cette étude est de montrer l'origine génétique de l'anosmie et de déterminer son mode de transmission chez ces populations.Patients et Méthodes : C'était une étude prospective et descriptive menée dans la ville de N'Djaménaau Tchad. L'étude a concerné 146 personnes anosmiques, toutes des Hadjaraï d'au moins 15 ans. Pour chaque patient, un pedigree a été réalisé. Nous avons tiré au hasard 30 pedigrees pour l'étude.Résultats : L'ensemble de 30 pedigrees était composé de 485 personnes dont 161 anosmiques (93 hommes et 68 femmes).Dans tous les pedigrees, une personne anosmique de la deuxième ou troisième génération avait toujours un des parents anosmique excepté deux individus. La transmission de l'anosmie était verticale dans presque tous les pedigrees. Trois cas probables d'anosmie à pénétrance incomplète avaient été notés, donnant la pénétrance de la maladie à 0,98. La quasi-totalité des enfants issus des couples sains étaient indemnes. Dans trois quart des cas, les hommes malades mariés à des femmes sainesle transmettaient à leurs fils. Dans tous les pedigrees, une transmission de la maladie de père à enfants avait été notée.Conclusion : L'anosmie observée chez les « Hadjaraï » est d'origine génétique et se transmettrait selon le mode autosomique dominant, à pénétrance presque complète et à expressivité peu variable

Formes familiales du syndrome de Gougerot-Sjögren : étude de 22 familles multiplex

Introduction : Les facteurs génétiques du SGS, outre les modèles animaux, sont déterminés par le biais de leurs formes familiales. L'objectif de ce travail était d'étudier les aspects phénotypiques des formes familiales du SGS. Patients et méthodes : Etude réalisée dans le service de Rhumatologie du CHU Aristide Le Dantec de Dakar entre Janvier 2013 et Mars 2016, où nous avons colligé les observations de familles multiplex de SGS répondant aux critères de consensus de 2002.Résultats : Vingt-deux familles ont été colligées à partir de 22 propositus (17 femmes et 5 hommes), d'âge moyen de 31,5 ans au début apparent de la maladie. Le SGS chez ces propositus était primitif dans 8 cas et secondaire à une PR dans 14 cas. Les familles totalisaient 921 membres. Soixante- quinze (54 femmes et 21 hommes), y compris les cas index présentaient un SGS (54 primitifs et 21 secondaires), soit une prévalence de 8,14 %. Les apparentés de premiers degré atteints étaient au nombre de 46 (85%). Les autres maladies auto- immunes associées étaient une PR (16 cas), un lupus systémique (1 cas), une polymyosite (1 cas), une sclérodermie systémique (1 cas), un vitiligo (1 cas) et une maladie de Basedow (1 cas). Les autres affections répertoriées étaient : lymphome oculaire (1 cas), cancer du col de l'utérus (1 cas). L'évolution sous traitement fut favorable, sauf chez 1 cas décédé. Conclusion : Le caractère familial du SGS chez nos malades plaide en faveur de l'implication de facteurs génétiques dans le déterminisme de la maladie

Rheological variations among Nigerians with different hemoglobin genotypes

A total of one hundred and Forty-five (145) subjects comprising of 50 homozygous Hemoglobin A subjects (HbAA); 50 heterozygous hemoglobin AS (HbAS) subjects and 45 homozygous hemoglobin S (HbSS) subjects were recruited for this study with a view to ascertain variations in the Hemorheological values possibly associated with the inherited hemoglobin genotype. Some Hemorheological determinants such as whole blood viscosity (WBV) and plasma viscosity (PV) and Plasma Fibrinogen Concentration (PFC) were measured with standard methods. We recorded a relatively unchanged whole blood viscosities in subjects with various hemoglobin genotypes (AA; AS and SS; P0.05; respectively). Also; there were no significant differences in PV values of HbAA and HbAS while there were significant increases in PV and PFC of HbSS compared with others (P0.05; respectively). However; relative erythrocyte viscosity (REV) of HbSS became significantly reduced when repeated with saline after replacing plasma with saline (P0.05; respectively); to ascertain the erythrocytic cellular viscosity. We conclude that increased plasma viscosity coupled with that of PFC in HBSS could be due to plasmatic components and that cellular rheologic properties of the erythrocytes may be dependent on its content of hemoglobin while whole blood viscosities are stable in native blood irrespective of haemoglobin genotypes

Constitutional; Legal and Regulatory Imperatives for the Renewed Care and Prevention of Congenital Disorders in South Africa

Medical genetic services for the care and prevention of congenital disorders have declined significantly in recent years due to competing health priorities; with previously developed services becoming compromised. With an infant mortality rate of 28/1 000 live births; South Africa (SA) has passed the threshold of 40/1 000 when such services should be implemented. This article outlines the international background and SA legislative framework for medical genetic services and their implementation. International; regional and national conventions; legislation; and policy were studied for relevance to genetic services and their implementation was evaluated; including a comparison of sector capacity between 2001 and 2015. A comprehensive legislative and regulatory framework exists in SA for the provision of medical genetic services; but implementation has been fragmented and unsustained. Congenital disorders and genetic services are not prominent in national strategies and excluded from interventions aimed at combating child mortality and non-communicable diseases. Capacity today is at a lower level than in 2001. The failure to recognise the burden of disease represented by congenital disorders is the underlying reason for the implementation and service shortfall. Child mortality rates have stagnated since 2011 and can be significantly further reduced by prioritising healthcare issues other than HIV/AIDS; including congenital disorders. It is now an imperative that SA responds to World Health Assembly Resolution 63.17 and prioritises congenital disorders as a healthcare issue; providing services to uphold the dignity and human rights of the most vulnerable members of society

Clinical Findings and Genetic Screening for Copy Number Variation Mutations in a Cohort of South African Patients with Parkinson's Disease

BACKGROUND:Parkinson's disease (PD); with a prevalence of up to 4% in Western countries; appears to be less common in Africa; possibly in part because of genetic factors. African studies investigating the genetic causation of PD are limited. OBJECTIVE:To describe the clinical and genetic findings in a group of black South African patients with PD.METHODS:All black African patients with PD from a tertiary hospital neurology clinic were examined. Symptoms were scored according to the Unified Parkinson's Disease Rating Scale (UPDRS); and patients were classified according to motor features. Genomic DNA was extracted and multiplex ligation-dependent probe amplification was used for detection of copy number variation (CNV) mutations in the known PD-causing genes.RESULTS:Sixteen patients were identified (ages 56 - 82 years). Three had a family history of PD. Classification into motor subtypes showed 44% mixed; 31% akinetic-rigid; and 25% tremor-dominant subtypes. UPDRS scores ranged from 7 to 88; with dementia in 20%. No patient had G2019S LRRK2 and A30P SNCA mutations; and all except one had no CNV mutations in the known PD-causing genes. A female patient (age of onset 50 years; no family history) had a parkin gene heterozygous deletion of exon 4. She had hyperreflexia; bilateral Hoffmann's reflexes; normal plantar responses and no dystonia.CONCLUSION:This group of black African patients showed similar characteristics to patients in Western studies; possibly with a higher proportion having tremor-dominant disease. Genetic analysis showed one parkin gene mutation. The limited knowledge on PD-causing genes and mutations in black populations warrants further studies involving next-generation sequencing approaches

Family history as a risk for early-onset type 2 diabetes in Kenyan patients

Early-onset type 2 diabetes is regarded as disease occurring before the age of 40 years. It is well described, and increasing in prevalence, but there is little information from Africa. We therefore assessed the prevalence of early-onset type 2 diabetes in Nairobi, Kenya; and investigated its association with family history. Of 140 patients with type 2 diabetes, 33 (24%) had an early onset. There was a positive family history of diabetes in 85% of those with early onset, compared with 56% of those with usual onset (p=0.009). This suggests that relatives of those with early-onset type 2 diabetes should have regular diabetes screening

Epidemiological African Day for Evaluation of Patients at Risk of Venous Thrombosis in Acute Hospital Care Settings : Cardiovascular Topic

Introduction : This study aimed to identify patients at risk for venous thromboembolism (VTE) among all patients hospitalised; and to determine the proportion of at-risk hospital patients who received effective types of VTE prophylaxis in sub-Saharan Africa (SSA). Methods: A multinational; observational; cross-sectional survey was carried out on 1 583 at-risk patients throughout five SSA countries. Results: The prevalence of VTE risk was 50.4 overall; 62.3 in medical and 43.8 in surgical patients. The proportion of at-risk patients receiving prophylaxis was 51.5 overall; 36.2 in medical and 64 in surgical patients. Low-molecular weight heparin was the most frequently used prophylactic method in 40.2 overall; 23.1 in medical and 49.9 in surgical patients. Discussion: This study showed a high prevalence of VTE risk among hospitalised patients and that less than half of all at-risk patients received an American College of Clinical Pharmacy-recommended method of prophylaxis. Conclusion: Recommended VTE prophylaxis is underused in SSA

Clinical and Genetic Diagnosis of Multiple Osteochondromas in Rwandan Patients

Multiple Osteochondromas (MO) or hereditary multiple exostoses (HME) is an autosomal dominant skeletal disorder mainly characterized by multiple osteochondromas predominantly located at the growth plates of long bones. MO is a genetically heterogeneous disorder and results from mutations in EXT1 and EXT2 genes located on chromosome 8q23-q24 and 11p11-p12. We hereby report a case of a 23-year-old girl who presented characteristic clinical and radiological features of MO. The same clinical signs were observed in her relatives. The p.Arg340Cys mutation in the EXT1 gene was found in the proband confirming the clinical diagnosis. A surgical management was carried out in all affected bones which consisted of excision of the bigger and pain full osteochondromas. The patient was informed of her problem and genetic counseling was offered to the family's members

Uptake of Genetic Counselling Services by Patients with Cystic Fibrosis and Their Families

Background: Although cystic fibrosis (CF) is a common genetic condition; genetic counselling services appear to be underutilised by affected families. The aim of this study was to determine the uptake of genetic counselling and mutation testing for CF by relatives of affected individuals; and the impact of introducing hospital-based genetic counselling services.Method: The files of 153 families seen for genetic counselling for CF by staff of the Division of Human Genetics; School of Pathology; University of the Witwatersrand; and the National Health Laboratory Service (NHLS) in Johannesburg; were retrospectively reviewed from 1990 to 2006; the year when hospital-based genetic counselling services were introduced.Results: Parents of CF probands were the largest single group (35) of counsellees. Most individuals (66) attended genetic counselling to gather information. Most had been referred by medical specialists (56). Only 10 of referrals originated from general practitioners. On average; from 1990-2005; six families received genetic counselling annually; whereas in 2006; 58 families were seen. In 140 unrelated families; 1 991 relatives with carrier risks of ? 25 were identified. Only 11of these relatives underwent mutation testing; and eight per cent received genetic counselling through our division over the review period.Conclusion: Overall; referrals of family members (of affected CF individuals) to genetic counselling; by general practitioners; are poor. Uptake of genetic counselling services is greater when such services are integrated into hospital-based CF management clinics; than when offered elsewhere. The low uptake of mutation testing and genetic counselling by at-risk relatives is a concern; since these relatives are at high risk of having affected children; if their partners are CF carriers. Education of affected individuals; their close relatives; and medical practitioners; should be prioritised. This will ensure referral to genetic counselling for discussion about the risks of and available testing for CF; and other genetic conditions

Plasmodium falciparum : taxonomie et genetique; apercu des questions actuelles

La structure genetique des populations naturelles de plasmodium falciparum est actuellement mal connue; et la nouvelle hypothese generale concernant l'importance de la reproduction clonale chez les protozoaires parasites qui est maintenant proposee pour ce plasmodium par certains protozoologistes; peut apporter une nouvelle vision des structures de populations de cet hematozoaire. Si elle se confirme; cette hypothese aura obligatoirement de grandes consequences taxonomiques et medicales

Quelques donnees cytogeniques sur le complexe anopheles gambiae au Sud-Cameroun

Les auteurs presentent des resultats originaux sur l'appartenance specifique de membres endophiles du complexe anopheles gambiae; recoltes au Cameroun dans les regions du Centre et de l'Ouest. Dans tous les cas; il s'agit d'anopheles gambiae sensu stricto. La reforme chromosomique foret predomine dans tous les prelevements realises. Dans la region de l'Ouest la reforme savane; tres minoritaire; est observee. L'absence d'anopheles arabiensis et d'anopheles melas est discutee

Interet de l'epidemiologie appliquee aux maladies parasitaires

De nombreuses maladies transmissibles; dont les maladies parasitaires; sont distribuees de maniere heterogene dans les populations exposees; on constate en particulier des concentrations familiales que les facteurs de milieu n'expliquent qu'en partie comme dans l'exemple du paludisme; particulierement etudie a l'OCEAC; des modeles experimentaux animaux peuvent egalement avoir mis en evidence des facteurs genetiques intervenant dans la susceptibilite a la maladie

Independent divergences in the CD4 binding site and V3 loop encoded in two seroprevalent Ugandan HIV-1 clinical isolates

"Two major epitopes expressed in HIV-1 have been recently shown to play a central role in virus neutralization. One of these important specificities is a type-specific or group-specific; principal neutralizing determinant (PND) located in the V3 loop of gp120. The other is a more broadly neutralizing determinant associated with the CD4 binding site. Structural and serological studies of the variation in these epitopes have become important in vaccine research. This report describes the analysis of the DNA clones encoding a region of gp120 that overlaps the V3 loop and the putative CD4 recognition site in two new African isolates; UG06c and UG23c. Phylogenetic analyses of the DNA sequences showed that the new African isolates clustered with two very distinct subtypes of HIV-1. UG06c was grouped with U455; D687; and Z321; previously classified as ""HIV-1 subtype A"" in the AIDS and human retroviruses database; and UG23c was grouped with MAL; JY1; NDK; ELI; and Z2Z6 classified as ""HIV-1 subtype D."" Considerable variation was apparent in the V3 loop. The divergence included the presence of the hexapeptides GP-GRSF and GLGQAL at the cap of the loop in UG06c and UG23c; respectively. The GPGR tetrapeptide in UG06c formed a beta-turn configuration similar to that of MN or IIIB. The beta-turn was not found to be a likely conformation for GLGQ. The amino acids previously implicated in CD4 binding and the associated neutralizing activity were relatively conserved. To assess a possible impact of the sequence and conformational variations on serological reactivity; UG06c and UG23c were subjected to neutralization assay.(ABSTRACT TRUNCATED AT 250 WORDS)"