Arnold L. Christianson

Folate status, homocysteine metabolism, and methylene tetrahydrofolate reductase genotype in rural South African blacks with a history of pregnancy complicated by neural tube defects.

The birth incidence of neural tube defects (NTDs) in South Africa is threefold to sixfold higher in rural compared with urban blacks. We investigated whether folate deficiency and aberrant homocysteine metabolism could explain the high NTD incidence in rural black populations. Plasma folate and total homocyst(e)ine (tHcy) concentrations were determined in apparently healthy rural black women (n = 107), rural black women with a history of pregnancy complicated by NTDs (n = 54), and urban blacks (n = 101). Methionine load tests were performed on the 54 women with a history of NTD-affected pregnancy and 54 controls matched for age and body mass. The presence of the 677C --> T mutation in the methylene tetrahydrofolate reductase (MTHFR) gene was investigated in both groups by a polymerase chain reaction (PCR) of genomic DNA and HinfI digestion of the PCR product. Apparently healthy urban black women (n = 101) had a lower (P < .001) plasma folate concentration compared with rural black women (n = 107). Women with a history of NTD-affected pregnancy did not differ significantly from controls with respect to plasma folate, fasting homocyst(e)ine, methionine, and the post-methionine load increase in plasma homocyst(e)ine. More than 50% of both of the latter groups had a post-methionine load increase in plasma tHcy less than the fifth percentile as observed in a healthy white control group. No homozygotes for the 677C --> T mutation in the MTHFR gene were found in black mothers with NTD-affected offspring or controls. It is concluded that black urbanization is characterized by a diminished folate status that is paradoxically associated with a lower NTD birth incidence. Homozygosity for the 677C --> T mutation in the gene coding for MTHFR does not constitute a genetic risk factor for NTDs in blacks. No aberrant homocysteine metabolism could be demonstrated in black women with NTD-affected pregnancies.

Services for the Prevention and Management of Genetic Disorders and Birth Defects in Developing Countries

The benefits of the enormous progress in medical genetics during the past two decades in industrialized nations have had limited impact in developing countries, where more than 80% of the world’s population lives. To assess the status of genetic services in developing countries, the World Health Organization (WHO) and the World Alliance of Organizations for the Prevention of Birth Defects (WAOPD) convened a group of experts in medical genetics who either work in, or are familiar with, the social, economic and health problems of developing countries (see Appendix) in The Hague from 5 to 7 January 1999. The purpose of the meeting was to review the current status of genetic services in the developing world and to make recommendations to further the implementation of programs for the management and prevention of genetic disorders and birth defects at the primary health care and community levels in those countries.

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.

Development of a Primary Health Care Clinical Genetic Service in Rural South Africa – The Northern Province Experience, 1990–1996

The development of medical genetic services is not considered a priority in developing nations. However, many such countries are presently undergoing an epidemiological transition resulting in genetic disorders and birth defects becoming conditions that are attaining public health significance. South Africa is one such country. This paper documents the development, patient profile and experience gained in trying to establish a primary health care genetic/disability service in the country’s rural Northern Province.

From DNA to the Community

Accessible online at: www.karger.com/journals/cmg Daniel Gaudet, MD, PhD Organizing Committee Chairman, CORAMH Chairman of the Board The Corporation for Research and Action on Hereditary Diseases Jonquière, Québec (Canada) Tel. +1 418 541 1077, Fax +1 418 541 1116, E-Mail dgaudet@saglac.qc.ca Conference hosted by The Corporation for Research and Action on Hereditary Diseases (CORAMH) and Health Canada

Community Genetics in South Africa

The development of medical genetics in South Africa paralleled in many respects that of the industrialized nations. In the early 1990s the concept of community genetic services to cater for the needs of the majority and mainly rural population of South Africa was conceived. Subsequently, through clinical genetic outreach programs, significant developments in the principles, practice and policy for the initiation and development of a national medical genetic service based on primary health care has been achieved.

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.