Glutaric aciduria type 1 in South Africa-high incidence of glutaryl-CoA dehydrogenase deficiency in black South Africans.

Glutaric Aciduria type 1 (GA 1) is an inherited disorder of lysine and tryptophan catabolism that typically manifests in infants with acute cerebral injury associated with intercurrent illness. We investigated the clinical, biochemical and molecular features in 14 known GA 1 patients in South Africa, most of whom were recently confirmed following the implementation of sensitive urine organic acid screening at our laboratory. Age at diagnosis ranged from 3days to 5years and poor clinical outcome reflected the delay in diagnosis in all but one patient. Twelve patients were unrelated black South Africans of whom all those tested (n=11) were found homozygous for the same A293T mutation in the glutaryl-CoA dehydrogenase (GCDH) gene. Excretion of 3-hydroxyglutarate (3-OHGA) was >30.1µmol/mmol creatinine (reference range <2.5) in all cases but glutarate excretion varied with 5 patients considered low excretors (glutarate <50µmol/mmol creatinine). Fibroblast GCDH activity was very low or absent in all of five cases tested. Heterozygosity for the A293T mutation was found 1 in 36 (95% CI; 1/54 - 1/24) unrelated black South African newborns (n=750) giving a predicted prevalence rate for GA 1 of 1 in 5184 (95% CI; 1/11664 - 1/2304) in this population. GA 1 is a treatable but often missed inherited disorder with a previously unrecognised high carrier frequency of a single mutation in the South African black population.

Association between the 4 bp proinsulin gene insertion polymorphism (IVS-69) and body composition in black South African women.

The objective of the study was to examine the association between a functional 4 bp proinsulin gene insertion polymorphism (IVS-69), fasting insulin concentrations, and body composition in black South African women. Body composition, body fat distribution, fasting glucose and insulin concentrations, and IVS-69 genotype were measured in 115 normal-weight (BMI<25 kg/m2) and 138 obese (BMI>or=30 kg/m2) premenopausal women. The frequency of the insertion allele was significantly higher in the class 2 obese (BMI>or=35 kg/m2) compared with the normal-weight group (P=0.029). Obese subjects with the insertion allele had greater fat mass (42.3+/-0.9 vs. 38.9+/-0.9 kg, P=0.034) and fat-free soft tissue mass (47.4+/-0.6 vs. 45.1+/-0.6 kg, P=0.014), and more abdominal subcutaneous adipose tissue (SAT, 595+/-17 vs. 531+/-17 cm2, P=0.025) but not visceral fat (P=0.739), than obese homozygotes for the wild-type allele. Only SAT was greater in normal-weight subjects with the insertion allele (P=0.048). There were no differences in fasting insulin or glucose levels between subjects with the insertion allele or homozygotes for the wild-type allele in the normal-weight or obese groups. In conclusion, the 4 bp proinsulin gene insertion allele is associated with extreme obesity, reflected by greater fat-free soft tissue mass and fat mass, particularly SAT, in obese black South African women.

Genetic variation and population structure in remnant populations of black rhinoceros, Diceros bicornis, in Africa.

Black rhinoceros (Diceros bicornis) are one of the most endangered mammal species in Africa, with a population decline of more than 96% by the end of the last century. Habitat destruction and encroachment has resulted in fragmentation of the remaining populations. To assist in conservation management, baseline information is provided here on relative genetic diversity and population differentiation among the four remaining recognized subspecies. Using microsatellite data from nine loci and 121 black rhinoceros individuals, and comparing the results with those of other African species affected in similar ways, Diceros bicornis michaeli retained the most genetic diversity (heterozygosity 0.675) compared with Diceros bicornis minor (0.459) and Diceros bicornis bicornis (0.505), suggesting that the duration of the known bottlenecks in these populations has only had a limited impact on diversity. Comparable and moderate degrees of population differentiation were found between D. b. minor, D. b. bicornis and D. b. michaeli. Results from the single sample available of the most endangered subspecies, Diceros bicornis longipes, showed the least diversity of all individuals examined. This information should assist conservation management decisions, especially those affecting population viability assessments and selection of individuals for translocations, and will also facilitate subspecies identification for ex situ individuals of uncertain origin.