Galactosemia: evidence for a structural gene mutation.

Identical immunoprecipitin reactions appeared in double immunodiffusion between rabbit anltibodies to human galactose-1-phosphate uridyl transferase and red cell preparations from both normal and galactosemic individuals. The galactosemic erythrocyte preparations quantitatively absorbed the antiboy that immunoprecipitates enzymatically active galactose-1-phosphate uridyl transferase.

Galactokinase: evidence for a new racial polymorphism.

Activities of galactokinase and galactose-1-phosphate uridyltransferase in red cells were assayed in a mixed racial population of 645 pregnant women. The distribution of individual transferase activities for black subjects was the same as that for whites. In contrast, the distributions of individual galactokinase activities differed significantly in blacks and whites, the mean for the black population being 30 percent lower than the mean for the white population. The same racial difference was found when red cell galactokinase activity was examined in males and in newborns. Because low-, intermediate-, and high-galactokinase activities appear to segregate within several black families, this observed difference suggests a new, racially determined enzyme polymorphism.

Mucopolysaccharidosis in a cat with arylsulfatase B deficiency: a model of Maroteaux-Lamy syndrome.

A Siamese cat that presented clinical signs similar to those seen in humans with mucopolysaccharidoses was studied. The animal excreted increased amounts of polymeric glycosaminoglycans in the urine, consisting almost entirely of dermatan sulfate. Electron microscopy of circulating polymorphonuclear leukocytes revealed the presence of many membrane-bound lamellar inclusion bodies. Sulfate incorporation studies with cultured skin fibroblasts indicated defective glycosaminoglycan degradation. These cells showed a deficiency in arylsulfatase B activity. The disorder appears similar or identical to the Maroteaux-Lamy syndrome described in humans.

Galactose-1-phosphate uridyltransferase and galactokinase activity in cultured human diploid fibroblasts and peripheral blood leukocytes. I. Analysis of transferase genotypes by the ratio of the activities of the two enzymes.

The specific activities of galactokinase and galactose-1-phosphate uridyltransferase were determined in peripheral blood leukocytes directly after separation from whole blood, and in cultured skin fibroblasts at various times during the subculture growth period. Growth curves were obtained for fibroblasts based on three different parameters: direct cell counts, total protein, and total deoxyribonucleic acid (DNA) content. At the time in culture when the specific activity of both enzymes was maximal and least variable, the ratio of transferase to galactokinase correlated well with the transferase genotypes of the original tissue donors. Leukocyte transferase: galactokinase ratios gave a similar distribution pattern. Whereas transferase activity in both fibroblasts and leukocytes was similar, galactokinase was approximately three times as active in fibroblasts as in leukocytes. All fibrobast cell strains tested had similar galactokinase activity regardless of transferase genotype.The kinetic properties of fibroblast galactokinase were examined. Galactose-1-phosphate inhibits galactokinase activity in both normal and galactosemic cell strains, whereas other glycolytic intermediates have no effect. There was no detectable transferase activity in eight galactosemic (Gt(G)/Gt(G)) cell strains when transferase activity was maximal in cell strains of other transferase genotypes. Inhibitors responsible for the absence of transferase activity could not be demonstrated. In addition, transferase activity in galactosemic cell lysates was not observed in cells during logarithmic growth; measurable uridine diphosphate galactose (UDPgal) pyrophosphorylase activity was found in human diploid fibroblast cultures, as well as significant levels of endogenous uridine triphosphate (UTP) in lysates of fibroblast cultures.

Familial partial trisomy of the long arm of chromosome 10 (q24-26).

Two fourth cousins with a strikingly similar pattern of malformation and who have an unbalanced translocation (46, XY, -17, +t (17p; 10q) are described. From an analysis of the phenotypes of these patients and others reported with 10q trisomy, we propose that the trisomy 10q 24-26 syndrome includes: growth and mental retardation, a characteristic facies (microcephaly, flat face with spacious forehead, small nose, depressed nasal bridge, arched wide-spaced eyebrows, blepharophimosis, microphthalmia, low-set ears, bow-shaped mouth with prominent upper lip, micrognathia), palate anomalies (high-arched cleft or agenesis), congenital heart disease, and anomalies of the hands and feet. Anomalies common to the cousins, but not described in other patients with trisomy 10q, are believed to be expressions of a partial monosomy of 17p.

Deletion mapping: further evidence for the location of acid phosphatase (ACP1) within 2p23.

The human red cell acid phosphatase (ACP1) locus was assigned to region 2p23 leads to 2pter by Ferguson-Smith et al [3], more specifically to 2p23 by Hamerton et al [5]. We describe two unrelated patients with deletion of chromosome 2, with similar breakpoints in the distal portion of band p23 (del(2) (p23)). ACP1 typing in both patients revealed heterozygous BA phenotypes. Thus, we assign the locus for ACP1 to the distal portion of 2p23.

Fetal renal malformation following treatment of Hodgkin's disease during pregnancy.

A case of human fetal renal maldevelopment following the administration of nitrogen mustard, vincristine, procarbazine, and prednisone in early pregnancy for therapy of Hodgkin's disease is reported. While these agents have been shown to be teratogenic in animal experiments, adverse fetal effects following their use during early human pregnancy have not been described. In spite of this previous experience, it has generally been recommended that these agents be withheld during the first trimester of pregnancy because of their presumed teratogenic potential. This case would seem to reinforce this recommendation.

An evaluation of cytogenetic analysis as a primary tool in the assessment of recurrent pregnancy wastage.

Cytogenetic evaluation of couples with recurrent pregnancy wastage is frequently performed only after other possible etiologic factors have been excluded. Previous reports of studies using conventional and G-banding chromosome techniques in these couples have shown a higher frequency of translocations than that found in the general population. In the study reported here, both conventional and G-banded chromosome analyses were performed as a primary method of evaluation in 34 couples with recurrent fetal loss not ascertained by the birth of a child with a diagnosed chromosome disorder. Balanced translocations were found in 5 partners of the 34 couples studied. In only 2 of these cases was the translocation detected by conventional chromosome analysis. These results suggest that G-banded chromosome analysis should be a useful tool in the initial evaluation of couples with recurrent fetal wastage, rather than being recommended only after extensive investigation of other factors is unrewarding. The reproductive counseling of couples with a translocation detected on this basis is discussed.

Amniography for the early detection of neural tube defects.

Among the methods available for the midtrimester diagnosis of neural tube defects, it has been suggested that amniography be used to determine the presence of meningomyelocele. Twelve studies are reported in which the procedure was utilized. In 3 cases, a neural tube defect was present but was not detected by this method. The experience reported here challenges the value of this procedure and suggests that it should be evaluated further by utilizing it in cases where a positive diagnosis has been made by other methods and pregnancy termination is to be performed.

Glk: a locus controlling galactokinase activity in the mouse.

Inbred strains of mice exhibited significant variation in whole blood galactokinase (GALK) activity. Activities tend to cluster into two classes, one class having approximately twice the activity of the other. Hybrids (F1) between "high" and "low" strains have activity intermediate between the parental activities. Two sets of recombinant inbred (RI) lines were developed by brother-sister mating, beginning with F2 generations of crosses between different pairs of high and low GALK activity strains. The RI lines segregated in terms of GALK activity, indicating single gene inheritance; this galactokinase locus has been designated Glk. The strain distribution patterns of both RI series agreed closely with esterase-3 (Es-3) alleles of the respective parental strains (31/34 independently derived strains were concordant for Es-3 and Glk genotypes), a finding consistent with a map distance between loci of 2.5 cM. Es-3 has been located on the distal end of chromosome 11. Glk, with its alleles Glka (lower activity) and Glkb (higher activity), is therefore assigned to the same region.

Characterization of normal and abnormal variants of galactose-1-phosphate uridylyltransferase (EC 2.7.7.12) by isoelectric focusing.

Isoelectric focusing (IEF) in polyacrylamide gels has been used to study the isozymes of human galactose-1-phosphate uridylyltransferase (GALT) in erythrocytes and fibroblasts. In addition to the usefulness of IEF in differentiating normal, Duarte variant, and galactosemic homozygotes and heterozygotes, the ability of IEF to distinguish the residual GALT activity in two different galactosemic fibroblast lines and in revertants from them is demonstrated.