Effect of three low-dose fish oil supplements, administered during pregnancy, on neonatal long-chain polyunsaturated fatty acid status at birth.

Adequate long-chain polyunsaturated fatty acid (LCP) status during pregnancy is important. We studied the effect of three low-dose fish oil supplements, administered during uncomplicated pregnancy, on neonatal LCP status at term delivery. Supplements were administered from the second trimester to delivery, either as fish oil capsules ("fish-1": 336 mg LCPomega3, n=15; and "fish-3": 1,008 mg LCPomega3, n=20) or milk-based supplement ("Mum": 528 mg LCPomega3, n=24). Fifty-seven untreated women served as controls. Fatty acids of umbilical veins (UV) and arteries (UA) were measured. The fish-1 group showed no differences, compared to controls. The Mum group had higher 20:5omega3, 22:5omega3, 22:6omega3, LCPomega3 and 22:6omega3/22:5omega6 in UV and UA. The fish-3 group had higher 22:5omega3 and 22:6omega3 (UA), LCPomega3 and 22:6omega3/22:5omega6 (UV and UA) and 20:3omega6 (UV). A 500-1000 mg daily LCPomega3 supplement, taken either as a milk-based supplement or fish oil capsules, effectively increases fetal LCPomega3 status, without affecting LCPomega6 status.

Persistent iron and folate deficiency in a patient with deletional hereditary persistence of fetal hemoglobin; the effect on the relative levels of Hb F and G gamma chains and the corresponding mRNAs.

We describe a Black female who has suffered for many years from an (often) severe anemia (Hb 5-9 g/dl) with iron deficiency (serum Fe 8 microg/dl; TIBC 462 microg/dl; ferritin 7 ng/ml or less) and folate deficiency. The patient had hypermenorrhea which was appropriately treated resulting in an increase in hemoglobin level but not affecting the Fe deficiency. Splenomegaly was present, perhaps resulting from a clay-eating habit, although this was consistently denied. The patient had an alpha-thalassemia-2 (-3.7 kb) trait and a deletional hereditary persistence of fetal hemoglobin (HPFH) (type II) which were inherited from her father. Over the last six years the level of Hb F varied between 8.5 and 16% (25-29% in the father), while the G gamma value was also low (15-22% versus 32-34% in the father). Comparable reductions were seen in the relative levels of gamma-mRNA and G gamma-mRNA. These data support results published by Adams et al who showed a severe reduction in Hb F level in another HPFH heterozygote with Fe deficiency; these investigations suggested that a reduction in alpha-globin synthesis resulted in preferential formation of alpha beta dimers rather than alpha gamma dimers. Our data suggest that the decrease of Hb F and G gamma levels is due to a reduction in gamma-mRNA formation, mainly of the G gamma type, rather than through a posttranslational mechanism alone.

Screening cord blood for hemoglobinopathies and thalassemia by HPLC.

We evaluated the use of an HPLC method for screening hemoglobins in cord blood. We studied the genotype frequencies of the structural hemoglobin variants HbS and HbC and the synthesis variants alpha- and beta(+)-thalassemia in babies born on Curaçao. During three months, 67.2% of all (748) newborns were screened: 122 (24.3%) had an abnormal hemoglobin pattern, of which 53 (43.4%) had a hemoglobinopathy (HbS or HbC), 64 (52.2%) had alpha-thalassemia (HbBarts greater than 0.5%, corresponding to heterozygous or homozygous alpha-thalassemia-2), and 5 (4.1%) had a hemoglobinopathy plus alpha-thalassemia. None of the newborns with heterozygous HbS and HbC had concomitant beta(+)-thalassemia. The population genotype frequency of heterozygous alpha-thalassemia-2 was calculated to be 30.7%. The data are in excellent agreement with those previously established for the adult population and those available from the black population in the United States and Jamaica. Based on the HPLC results, we estimate that 67.1% of newborns with heterozygous alpha-thalassemia-2 remain undetected. A coincidental finding was a relation between demonstrable alpha-thalassemia and short gestation. Because of its superior separating power and high sensitivity for quantifying relatively low percentages of hemoglobins in the presence of HbF0, the HPLC method was preeminently suitable for screening cord-blood samples.

Screening of cord blood for haemoglobinopathies and thalassaemia by high-performance liquid chromatography - abstract

A high-performance liquid chromatography (HPLC) method for the screening of haemoglobins in cord blood was evaluated and the gene frequencies of the structural haemoglobin variants HbS and HbC and the synthesis variants O- and á+ -thalassaemia were studied in babies born on the Caribbean island of Curacao, the Netherlands Antilles. In 3 months, 67.2 percent of all (748) newborns were screened and 122 (24.3 percent) had an abnormal haemoglobin pattern, of which 53 (43.4 percent) had a haemoglobinopathy (HbS or HbC), 64(52.2 percent) O-thalassaemia (Hb Barts > 0.5 percent, corresponding with heterozygous or homozygous O-thalassaemia-2) and 5 (4.1 percent) a haemoglobinopathy plus O-thalassaemia. None of the newborns with heterozygous HbS and HbC had concomitant á+-thalassaemia. The population genotype frequency of heterozygous O-thalassaemia -2 remain undetected. The data are in excellent agreement with comparable published results. The HPLC method proved pre-eminently suitable for the screening of cord blood samples. (AU)

The DNA deletion in an Indian delta beta-thalassaemia begins one kilobase from the A gamma globin gene and ends in an L1 repetitive sequence.

High fetal haemoglobin levels of 5-15% are present in adult heterozygotes for delta beta-thalassaemia as the result of large deletions of DNA. We have cloned DNA spanning the deletion breakpoint for a new Indian delta beta-thalassaemia associated with mild anaemia. The 5' breakpoint is at 42151 of GenBank file HUMHBB, which is about 1 kb 3' of the A gamma globin gene poly A site at 41003. On the 3' side of the breakpoint, the sequence is homologous to L1 (KpnI) repetitive DNA located 3.6-10 kb 3' of the beta-globin gene: Indian delta beta-thalassaemia DNA is 74% homologous to the inverted complement of HUMHBB from 69849 to 70020, followed by a region 78% homologous to the direct sequence of HUMHBB from 70534 to 71010. The precise location of the 3' endpoint of this deletion has not been determined, but it is within L1 sequences located more than 10 kb 3' of the beta-globin gene.

[Homozygote beta-thalassemia in 2 Dutch families]. / Homozygote beta-thalassemie in twee Nederlandse families.

beta-thalassaemia is a haematological disorder which is rare in The Netherlands although the influx of carriers from Mediterranean, West Indian, and South American countries has increased its frequency. Only a few homozygotes have been found among the original Dutch population. In this article, we describe the molecular abnormality observed in two such homozygotes. Both patients were mildly affected and had the same C-G mutation in the beta-globin gene promoter at position -87 relative to the Cap site of the beta gene. This mutation is known to cause a mild beta +-thalassaemia. Additional studies of the epsilon-gamma-delta-beta-globin gene complex on chromosome II, i.e. haplotype analyses, identified three different haplotypes in the two patients. However, crossovers might have been responsible for these differences because the 3' haplotype, which involves restriction sites within and 3' to the beta-globin gene, was the same for all four chromosomes in the two homozygotes.

Two different quadruplicated alpha globin gene arrangements.

The discovery of two different types of alpha globin gene quadruplication is reported. One with the alpha alpha alpha alpha (anti 3.7)/haplotype was present in four members of a Black family from Georgia, while a second with the alpha alpha alpha alpha (anti 4.2)/haplotype was observed in two members of an Indonesian family. Consistent clinical and haematological manifestations could be observed in these heterozygotes.

An elongated segment of DNA observed between two human alpha globin genes.

Detailed restriction enzyme analysis of the DNA from a Chinese female showed that one of her chromosomes had a greater than 17.5 kb deletion of DNA, including the psi alpha, alpha 2, and alpha 1 globin genes, which is present in many Southeast Asians with an alpha-thalassemia-1 chromosome. Her "normal" chromosome had the expected cluster of alpha-like globin genes (5'-zeta-psi zeta-psi alpha-alpha 2-alpha 1-3'), but the segment of DNA between the two alpha globin genes was elongated by some 0.5-0.7 kb. Analyses of various restriction sites suggested that this normal variant of the human alpha globin gene complex is due to a crossover between a normal chromosome with (alpha alpha) and a chromosome with an alpha-thalassemia-2 (-alpha 3.7) and an -alpha 2 alpha 1-hybrid gene.