Liver Transplantation for Severe Alcoholic Hepatitis: Report of a Single Center Pilot Program.

BACKGROUND: Liver transplantation (LT) can significantly improve mortality for severe alcoholic hepatitis (AH). However, this practice remains controversial. Our aim is to report the findings from our institution regarding outcomes for LT in severe AH and to discuss the results of a pilot program for discharging selected patients with close follow-up, in order to demonstrate sustained outpatient sobriety before listing. METHODS: Patient records were reviewed retrospectively from January 1, 2015 to January 17, 2018. The primary outcomes were patient and graft survival after LT. Secondary outcomes included relapse rates after LT, survival for those not transplanted, and reasons for denial among those not approved for transplant listing. RESULTS: A total of 18 patients with severe AH were considered for LT, of which 10 were transplanted and 8 were either denied transplantation or died before completing the evaluation. Patient and graft survival rates were 100% among those transplanted, and only 1 of the 10 patients (10%) returned to harmful drinking. In comparison, 6 of 8 (75%) of patients not transplanted died. Among the 10 patients transplanted, 4 were initially not approved for listing and were discharged with close follow-up, to demonstrate outpatient sobriety. All 4 of those patients demonstrated short-term abstinence and ultimately underwent transplantation, with no instances of relapse post-LT. CONCLUSIONS: Liver transplantation for AH can achieve excellent outcomes with low rates of relapse. Carefully selected patients can be discharged with close monitoring to demonstrate commitment to outpatient sobriety prior to transplant listing.

Ultrastructural investigation of Zimmermann-Laband syndrome.

Zimmermann-Laband syndrome (ZLS) is a very rare autosomal dominant inherited condition characterized by 3 major clinical findings of which gingival hyperplasia are always present. The great heterogenicity of the syndrome is illustrated by the numerous variable clinical findings described in the literature. The purpose of the study was to examine a patient diagnosed with ZLS and to describe possible new characteristics of this rare syndrome, including the ultrastructural morphology using a transmission electron microscope (TEM) of the gingival and dermal fibroblasts. The ultrastrucutral morphology as has not previously been described in the literature. Tissue was collected from the alveolar ridge and skin of the forearm for TEM. TEM studies indicated the presence of prominent fibroblasts situated among numerous regular dense connective tissue bundles. Genetic analysis showed a new chromosomal insertion, ins(12;8)(p11.2;q11.2q24.3), suggesting that the gene responsible for the syndrome lies on chromosome 8.

Children with intellectual disability in rural South Africa: prevalence and associated disability.

The objective of the present study was to determine the prevalence of intellectual disability (ID) and its associated disabilities in rural South African children aged 2-9 years. It was undertaken in eight villages in the district of Bushbuckridge, Northern Province, South Africa. A two-phase design was utilized. The first phase involved screening children on a house-to-house basis by interviewing mothers or caregivers using an internationally validated questionnaire for detecting childhood disability in developing countries. The second phase consisted of a paediatric/neurodevelopmental assessment of the children who screened positive. A total of 6692 children were screened; 722 (10.8%) had a paediatric evaluation and 238 children were diagnosed with ID, giving a minimum observed prevalence of 35.6 per 1000 children in this population. The prevalence of severe and mild ID was 0.64 per 1000 and 29.1 per 1000 children, respectively. The male:female ratio of children with ID was 3:2. In the affected children, a congenital aetiology for the ID was determined in 49 subjects (20.6%), an acquired aetiology in 15 (6.3%) and the aetiology was undetermined in 174 children (73.1%). Epilepsy (15.5%) and cerebral palsy (8.4%) were the commonest associated disabilities. The present study represents the first data on the prevalence of ID and associated disabilities in rural South African children. The prevalence of ID was comparable with results from a study performed in one other African country (Zambia) as well as those from other developing countries. The data provide an initial factual insight into ID and its associated disabilities for healthcare, social service and educational policy planners. This study provides a basis for the initiation and development of appropriate and integrated services for the best possible care of individuals affected with these disabilities, and for their possible prevention.

Clouston hidrotic ectodermal dysplasia (HED): genetic homogeneity, presence of a founder effect in the French Canadian population and fine genetic mapping.

HED is an autosomal dominant skin disorder that is particularly common in the French Canadian population of south-west Quebec. We previously mapped the HED gene to the pericentromeric region of chromosome 13q using linkage analysis in eight French Canadian families. In this study, we extend our genetic analysis to include a multiethnic group of 29 families with 10 polymorphic markers spanning 5.1 cM in the candidate region. Two-point linkage analysis strongly suggests absence of genetic heterogeneity in HED in four families of French, Spanish, African and Malaysian origins. Multipoint linkage analysis in all 29 families generated a peak lod score of 53.5 at D13S1835 with a 1 lod unit support interval spanning 1.8 cM. Recombination mapping placed the HED gene in a 2.4 cM region flanked by D13S1828 proximally and D13S1830 distally. We next show evidence for a strong founder effect in families of French Canadian origin thereby representing the first example of a founder disease in the south-west part of the province of Quebec. Significant association was found between HED in these families and all markers analysed (Fisher's exact test, P < 0.001). Complete allelic association was detected at D13S1828, D13S1827, D13S1835, D13S141 and D13S175 (P(excess) = 1) spanning 1.3 cM. A major haplotype including all 10 associated alleles was present on 65% of affected chromosomes. This haplotype most likely represents the founder haplotype that introduced the HED mutation into the French Canadian population. Luria-Delbrück equations and multipoint likelihood linkage disequilibrium analysis positioned the gene at the D13S1828 locus (likely range estimate: 1.75 cM) and 0.58 cM telomeric to this marker (support interval: 3.27 cM) respectively.

Epilepsy in rural South African children--prevalence, associated disability and management.

OBJECTIVE: To determine the prevalence of epilepsy and its associated disabilities in rural South African children aged 2-9 years. SETTING: Eight villages in the district of Bushbuckridge, Northern Province, South Africa. DESIGN: A two-phase design was used. The first phase involved screening children on a house-to-house basis by interviewing mothers or caregivers using an internationally validated questionnaire for detecting childhood disability in developing countries. The second phase consisted of a paediatric/neurodevelopmental assessment of the children who screened positive. RESULTS: A total of 6,692 children were screened; 722 (10.8%) had a paediatric evaluation and 49 (0.73%) had epilepsy. The lifetime and active prevalences of epilepsy in these children were 7.3/1,000 and 6.7/1,000 respectively. Associated developmental disability was recorded in 35 affected children (71.4%), including 8 (16.3%) in whom this was moderate to severe. More than a half of the children with epilepsy (57.1%) did not receive anticonvulsant medication. CONCLUSION: The prevalence of epilepsy in the rural childhood population investigated is higher than that recorded in most similar studies from sub-Saharan Africa, and the poor utilisation of appropriate anticonvulsant treatment is cause for concern. This study highlights the paucity of relevant information on the epidemiology of epilepsy in South Africa and that the system available for its management, especially in rural areas, appears to have functional deficiencies. Appropriate research is needed to identify the problems in service delivery and to enable the planning and implementation of an appropriate primary health care-based system for the diagnosis and management of epilepsy in children.

Medical genetics in primary health care.

Medical genetics has been at the forefront of developments in medicine for the last 50 years. This progress has mainly benefited industrialized countries. Due to continuing improvements in the socio-economic and health indices in developing nations more than half of them have now reached a stage where it has become relevant for them to initiate and develop medical genetic services. The WHO foresaw this eventuality in 1985 and further recognised the need to develop community based medical genetic services that are relevant to and can be incorporated into primary health care. The need for primary health care based medical genetic services has subsequently also been accepted in industrialized nations. This paper summarises those primary health care based interventions that can be undertaken to ensure the control of genetic disorders and birth defects.

X linked severe mental retardation, craniofacial dysmorphology, epilepsy, ophthalmoplegia, and cerebellar atrophy in a large South African kindred is localised to Xq24-q27.

To date over 150 X linked mental retardation (XLMR) conditions have been documented. We describe a five generation South African family with XLMR, comprising 16 affected males and 10 carrier females. The clinical features common to the 16 males included profound mental retardation (100%), mutism despite apparently normal hearing (100%), grand mal epilepsy (87.5%), and limited life expectancy (68.8%). Of the four affected males examined, all had mild craniofacial dysmorphology and three were noted to have bilateral ophthalmoplegia and truncal ataxia. Three of 10 obligate female carriers had mild mental retardation. Cerebellar and brain stem atrophy was shown by cranial imaging and postmortem examination. Linkage analysis shows the gene to be located between markers DXS424 (Xq24) and DXS548 (Xq27.3), with a maximum two point lod score of 3.10.

Acromelic frontonasal dysostosis.

We report on 3 male and 2 female infants with acromelic frontonasal dysostosis. All 5 had a frontonasal malformation of the face and nasal clefting associated with striking symmetrical preaxial polysyndactyly of the feet and variable tibial hypoplasia. In contrast, the upper limbs were normal. This rare variant of frontonasal dysplasia may represent a distinct autosomal-recessive disorder. We suggest that the molecular basis of this condition may be a perturbation of the Sonic Hedgehog (SHH) signalling pathway, which plays an important part in the development of the midline central nervous system/craniofacial region and the limbs.

Prader-Willi syndrome in South African patients--clinical and molecular diagnosis.

STUDY OBJECTIVE: To assess clinically South African patients with the putative diagnosis of Prader-Willi syndrome (PWS) and confirm this diagnosis by DNA/molecular analysis. DESIGN: Prospective, nationally based, combined clinical and laboratory study. MAIN RESULTS: Thirty-seven patients with a putative diagnosis of PWS were examined by clinical geneticists. Only 13 (35.1%) of these patients had the diagnosis of PWS confirmed by molecular analysis, and all 13 PWS patients had positive scores using the PWS consensus diagnostic criteria of Holm et al. The clinical features of the remaining 24 (64.9%) non-PWS patients were analysed and 23 did not have the neonatal, infantile and childhood features necessary to warrant consideration of a diagnosis of PWS; neither did they obtain a positive score according to Holm et al.'s criteria. CONCLUSION: PWS was confirmed in only 35% of South African patients with a putative PWS diagnosis, confirming that this condition is overdiagnosed and that the clinical diagnosis is difficult. Clinically, the diagnostic criteria of Holm et al. are of great assistance in making the diagnosis, but it remains essential to confirm the diagnosis by molecular analysis.

Down syndrome in black South African infants and children--clinical features and delayed diagnosis.

STUDY OBJECTIVE: Down syndrome (DS), the commonest cause of congenital developmental disability in developed countries, has only recently been shown to have an incidence in black South African neonates as high, and in some studies higher, than currently seen in First-World nations. It has also been reported that the mothers of black African DS newborns and medical and nursing staff have difficulty recognising and diagnosing DS in black neonates. The aims of this study were to document the clinical features of black DS infants and children, compare these to the features of previously documented DS infants and children from other ethnic groups, and finally to ascertain if and for how long the difficulties recorded in diagnosing DS in blacks extended into infancy or childhood. DESIGN: This was a prospective, genetic clinic-based study, entailing clinical evaluation of black DS infants and children 3 months of age and older, and the administration of a questionnaire to the mothers of these patients. SETTING: Genetics clinics at Kalafong and Ga-Rankuwa hospitals, Pretoria, and at Mankweng, Siloam, Groothoek, Nkhensani and Elim hospitals in the Northern Province. MAIN RESULTS: Fifty-five DS infants and children were assessed. Their clinical features were comparable to those of children from other ethnic groups. Congenital heart disease (CHD) was recorded in a significantly higher percentage of infants under 12 months of age (51.9%) than children 13 months of age or older (25%). Only 9 (16.4%) of these DS patients were clinically diagnosed in the neonatal period, and a further 18 (32.7%) at between 1 and 6 months of age. More than half (28 or 50.9%) were 7 months of age or older when initially clinically diagnosed. Maternal self-initiated awareness of a problem with their infant or child preceded clinical diagnosis in 32 (58.2%) patients. CONCLUSIONS: The difficulties experienced by medical and nursing staff in diagnosing DS in black neonates extends into infancy and childhood, despite the fact that the clinical features of black DS infants and children do not differ from those seen in DS patients in other ethnic groups. The prevalences of CHD in black DS infants and children suggest that CHD is a significant cause of mortality in black DS patients.

Sutural exostoses, rib hyperostoses, craniosynostosis, mental retardation with focal fat deposition: Proteus syndrome?

We report on a 3-year-old boy with cartilaginous exostoses of the cranial sutures, rib hyperostosis, macrocephaly, metopic craniostenosis, epibulbar dermoid, hyperpigmented macules on the neck, focal fat deposition, and mild mental retardation with marked speech delay. Several of these manifestations were reported previously as an "unknown" by Thanos et al. [1977], with additional clinical information and a diagnosis of Proteus syndrome [Cohen, 1993].

Family with autosomal dominant hidrotic ectodermal dysplasia: a previously unrecognised syndrome?

We describe a three-generation family with an autosomal dominant hidrotic ectodermal dysplasia consisting mainly of tricho- and onychodysplasia. One of the patients had supraventricular tachycardia, another had palpitations, and two others had sinus brachycardia. We consider that the clinical manifestations in this family differ significantly from those of the Clouston syndrome (their previous diagnosis) and places them in Group A, subgroup 1-3 (tricho-onychic) of the ectodermal dysplasia classification proposed by Freire-Maia and Pinheiro [1988, "Ectodermal Dysplasias"].

South African geneticists' attitudes to the present Abortion and Sterilisation Act of 1975.

STUDY OBJECTIVE: To ascertain the attitudes of clinical geneticists and genetic counsellors practising in South Africa to the current Abortion and Sterilisation Act of 1975 (the Act). DESIGN: Postal questionnaire. MAIN RESULTS: Ninety-two per cent of the questionnaires were returned, and the responses were comparable to those of the South African Society of Obstetricians and Gynaecologists in 1990 and the Society of Psychiatrists of South Africa in 1992. No respondent felt that the Act should be more restrictive, and only 4 (17.4%) felt that it was acceptable in its present form. Section 3(1)(c) of the Act, which relates to termination of pregnancy (TOP) on genetic grounds, was acceptable in its present form to 13 respondents (56.5%), but 16 (69.7%) considered that TOP on genetic grounds should not be curtailed in future legislation. CONCLUSION: The geneticists' attitudes to the present Act concurred with those of the obstetricians and psychiatrists previously documented, and confirmed the need for review of the Act. All three specialist groups appeared to support an increase in the indications for legal TOP rather than the introduction of TOP on request up to a specified post-conceptual age. With regard to Section 3(1)(c), the geneticists' responses indicated an acceptance of the limitations of the present Act, coupled with concern about the implications of future changes to this section of the Act.

Maternal non-recognition of Down syndrome in black South African infants.

Down syndrome (DS), one of the commonest causes of mental retardation in Caucasoids, has only rarely been described in Africa. In previous studies it was suggested that there may be clinical difficulties in making the diagnosis in African neonates. In the present study data were collected by means of a questionnaire administered partly before and partly after a genetic counselling session, to 35 mothers of African infants with DS. The results show that 83% of these mothers did not recognise any facial difference between their affected infant and other normal infants and 57% did not observe any other physical differences. After counselling, 40% of the sample still did not accept that their infant was different from other newborns. Only one mother was aware of infants with similar characteristics. These findings suggest that if mothers themselves cannot see the differences between their DS children and normal children, clinical diagnosis based on physical stigmata may be difficult. Furthermore, acceptance of the diagnosis may be retarded until delayed mile-stones can be observed in the affected infants.