Rabbit Anti-Human PGM1 Polyclonal Antibody Knockout Validated

As part of the Cornell-Bahia project on leishmaniasis, the people of Jacobina in the state of Bahia in northeastern Brazil were studied for five genetic polymorphisms: ABO blood groups, hemoglobin variants, PGM1, 6PGD, and adenylate kinase. A maximum likelihood method of calculation of frequency of genes for these traits indicates that the ancestry of the people is 45% African, 43% Portuguese, and 12% Brazilian Indian. This estimate is similar to previous estimates of admixture in the people of northeastern Brazil, except for more African and less Caucasian ancestry. Previous distance relationships, based upon physical traits only, showed the population of Jacobina to be similar to Seminole Indians of Florida and equally distant from Whites and Blacks. While not strictly comparable, the genetic and morphologic pictures of relationships are compatible and show concordance with surnames. The presence of Hemoglobin C and the frequencies of alleles of PGM1 and 6PGD in the Jacobina population are consistent with the greater importation of Africans into Brazil from Costa de Mina on the Guinea Coast than from Angola. (C) 1996 Wiley-Liss, Inc.

Purpose: Phosphoglucomutase-1 deficiency is a subtype of congenital disorders of glycosylation (PGM1-CDG). Previous case reports in PGM1-CDG patients receiving oral D-galactose (D-gal) showed clinical improvement. So far no systematic in vitro and clinical studies have assessed safety and benefits of D-gal supplementation. In a prospective pilot study, we evaluated the effects of oral D-gal in nine patients. Methods: D-gal supplementation was increased to 1.5 g/kg/day (maximum 50 g/day) in three increments over 18 weeks. Laboratory studies were performed before and during treatment to monitor safety and effect on serum transferrin-glycosylation, coagulation, and liver and endocrine function. Additionally, the effect of D-gal on cellular glycosylation was characterized in vitro. Results: Eight patients were compliant with D-gal supplementation. No adverse effects were reported. Abnormal baseline results (alanine transaminase, aspartate transaminase, activated partial thromboplastin time) improved or normalized already using 1 g/kg/day D-gal. Antithrombin-III levels and transferrin-glycosylation showed significant improvement, and increase in galactosylation and whole glycan content. In vitro studies before treatment showed N-glycan hyposialylation, altered O-linked glycans, abnormal lipid-linked oligosaccharide profile, and abnormal nucleotide sugars in patient fibroblasts. Most cellular abnormalities improved or normalized following D-gal treatment. D-gal increased both UDP-Glc and UDP-Gal levels and improved lipid-linked oligosaccharide fractions in concert with improved glycosylation in PGM1-CDG. Conclusion: Oral D-gal supplementation is a safe and effective treatment for PGM1-CDG in this pilot study. Transferrin glycosylation and ATIII levels were useful trial end points. Larger, longer-duration trials are ongoing.