Intravenous glucose tolerance and plasma insulin response in children with homozygous β-thalassaemia

ABSTRACT. Glucose tolerance and insulin secretion were studied after intravenous glucose load in 10 normal and 27 children with homozygous β-thalassaemia of whom 11 received 5–20 units of blood (1.25–5g total iron) and 16 received 50–60 blood units (12.5–40g total iron). Fasting blood glucose and insulin levels were similar in normal and thalassaemic children. Differences were found at 10 and 20 minutes of intravenous glucose administration both in glucose blood levels. (which were considerably higher) and insulin levels (which were significantly lower), in thalassaemic patients compared to normal children. Evidence of depression of pancreatic function was found in three out of 11 patients, with low and in three out of 16 patients with severe iron load. These findings suggest that in thalassaemia pancreatic impairment is not always directly related to the degree of iron overload.     

Successful pregnancy in β-thalassaemia major

ABSTRACT. Successful pregnancy is described in a patient with β-thalassaemia major, transfusion-dependent from four months of age and treated with desferrioxamine from 13 years of age. The pregnancy was concealed. No antenatal care was given nor any planned alteration in management of her thalassaemic state.     

Prenatal diagnosis of homozygous α°-thalassaemia by direct DNA analysis of chorionic villi in Singapore

Abstract First-trimester prenatal diagnosis by DNA analysis was carried out for seven pregnancies at risk for homozygous α°-thalassaemia. Transabdominal placental biopsy was carried out at 10–12 weeks'gestation. The presence of α-globin genes in the fetal DNA was determined by restriction endonuclease mapping and hybridization with cloned α-globin probe. Homozygous α°-thalassaemia was detected in two fetuses and the pregnancies were interrupted. α°-thalassaemiat in both cases was confirmed by electrophoresis of the umbilical cord blood where only haemoglobin Bart's was detected. The remaining five fetuses were diagnosed as normal or as possessing α°-thalassaemia-1 trait and the pregnancies are being carried to term. The use of DNA analysis in prenatal diagnosis of fetuses at risk for homozygous α°-thalassaemia enables detection of the haemoglobinopathy at 10 weeks'gestation.     

Vitamin D metabolites (25-hydroxyvitamin D, 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D) and osteocalcin in β-thalassaemia

Serum levels of the vitamin D metabolites 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D. and of osteocalcin. C-tenninal parathyroid hormone and other biochemical indices related to bone metabolism, were determined in two groups of patients with β-thalassaemia aged 5–10 years (summer 7.8 ± 0.4 years, mean ± SEM. and winter 7.7 ± 0.4 years, group A, n= 15) and 11–23 years (16.6 ± 0.9 and 15.7 ± 0.9 years in summer and winter, respectively, group B, n= 22). Emphasis was given to populations of school and adolescent ages and to the seasons of summer and winter when vitamin D status demonstrates the widest extremes. The mean serum levels of 25-hydroxyvitamin D in patients aged 5–10 years did not differ from those of controls during both seasons studied. In contrast, in the age group 11–23 years these levels were found to be lower in patients than in controls both in winter (10.6 ± 0.9ng/ml vs 15.0 ± 2.0ng/ml, p < 0.05) and summer (20.2 ± 2.1 ng/ml vs 27.1 ± 2.0ng/ml, p < 0.05). The serum concentrations of 24,25-dihydroxyvitamin D were lower in the thalassaemic patients than in controls in both age groups and both seasons. In the patients under 10 years of age the mean values of this metabolite in winter were 1.06 ± 0.17 ng/ml vs 1.68 ± 0.20 ng/ml in the respective controls (p < 0.05), and in summer 1.44 ± 0.11 ng/ml vs 2.35 ± 0.36 ng/ml in controls (p < 0.05). In the group of patients aged 11–23 years, the mean levels of 24,25-dihydroxyvitamin D were in winter 0.65 ± 0.12 ng/ml vs 1.12 ± 0.19 ng/ml (p < 0.05) in controls and in summer 1.34 ± 0.12 ng/ml vs 1.84 ± 0.20 ng/ml (p < 0.05). The 1,25-dihydroxyvitamin D concentrations in both thalassaemic patient groups were significantly no different from those in the respective control groups. Serum osteocalcin, C-terminal parathyroid hormone, calcium, inorganic phosphate and alkaline phosphatase levels in the patients studied were not significantly different from those in controls, except for calcium and phosphate in the older group. In the older group of thalassaemic patients, serum calcium was lower than in the controls (2.26 ± 0.03 vs 2.37 ± 0.03 mmol/1, p < 0.05) in summer and serum phosphate higher than in the controls in winter (1.47 ± 0.05 mmol/1 vs 1.27 ± 0.06 mmol/1. p < 0.05).     

Body proportions in individuals with Turner syndrome

The body proportions in 191 individuals with Turner syndrome (TS) were investigated. At 3 years of age the mean sitting height in TS was normal, thereafter trunk growth was impaired, resulting in a standard deviation score (SDS) of –2.4 in the adult. From 3 to 12 years of age the mean SDS of leg length increased from –2.7 to –3.6; and then fell to –2.5. At 3 years of age the ratio of sitting height to leg length was 3.2 standard deviations (SD) above the normal mean. Thereafter the ratio slowly approached the normal percentiles. It was +0.6 SD in 15-to 18-year-old women. Thereafter it increased to 1.7 for adults with TS. Knemometric measurements in 32 individuals with TS and 32 controls revealed that in TS the upper legs were relatively shorter than the lower legs. We conclude that children with TS, and to a lesser extent adults, have a disproportionately short stature with relatively short legs whereas body proportions are almost normal in adolescents.The investigators who participated in this study were: A. v. Trunenbroek, B. I. Otten, S. M. P. F. de Muinck Keizer-Schrama, S. L. S. Drop, H. A. Delemarre van den Waal, R. J. H. Odink, N. H. Drayer, W. Oostdijk, J. Stokvis-Brantsma, M. H. Gons, J. J. J. Waelkens, H. M. Reeser, and W. J. Gerver     

Body proportions in precocious puberty

Sitting height (SH) and sub-ischial leg length (SLL) were measured in 10 boys and 16 girls with precocious puberty; the patients were aged from 1.5 to 13.4 years at the time. Standard deviation scores (SDS) calculated for chronological age and bone age showed higher scores for SH than for SLL in all but two patients, both girls: the differences between the SDS for SH and SLL were more marked in the boys. The findings indicate that growth of the trunk is usually greater than growth of the legs in precocious puberty, particularly in boys.     

Serum interleukin-1β in neonatal sepsis

Serum levels of interleukin-1β (IL-1β) in newborn infants with septicaemia were measured and possible relationships between the clinical course of the infants, causative micro-organisms and IL-1β levels were investigated in a prospective study. The study groups comprised 49 newborn infants (25 mature, 24 premature) with proven sepsis and 40 healthy newborn infants (20 mature, 20 premature). Serum IL-1β levels were measured using the IL-1β immunoradiometric assay. The levels were found to be lower in neonates with sepsis (median 0.1 pg/ml) than in healthy controls (median 27.9 pg/ml) ( p <0.001). Non-significant trends towards lower levels were observed in children with shock and in non-survivors. No correlation was found between IL-1β and postnatal age, gestational age or the study weight of the patients. There was no significant difference in the serum IL-1β level in septic patients infected with Gram-positive bacteria and those infected with Gram-negative bacteria. The results show that the concentration of IL-1β is significantly decreased in preterm and term neonates with sepsis.     

Urinary β2 microglobulin in the newborn

ABSTRACT. Twelve full-term, healthy newborn infants had daily urinary β2 microglobulin, albumin and creatinine levels measured during the first five days of life.
A marked elevation in urinary β2 microglobulin was demonstrated. There was a marked variation from day to day with a range of 20–11,000μg/l. The relatively steady creatinine and albumin excretion levels suggest there is a true increased excretion of β2 microglobulin in the neonatal period with a tendency for the excretion rate to rise during the first five days of life.     

Relationship between SP1 polymorphism and osteoporosis in β-thalassemia major patients

Background: β-Thalassemia is an autosomal recessive disease characterized by defective β-globin chain production. Osteoporosis is an important cause of morbidity in patients with β-thalassemia major. The pathogenesis of reduced bone mineral density (BMD) is multifactorial. A range of genetics factors have been implicated in other populations of patients with osteoporosis. Polymorphism at the Sp1 binding site of the collagen type I A1 ( COLIA1 ) gene is thought to be an important factor in the development of osteoporosis.
Methods: Alleles S and s , detected by presence of a G or T nucleotide, respectively in a regulatory site of the COLIA1 gene were investigated in 37 β-thalassemia major patients with osteoporosis and 92 controls without osteoporosis or osteopenia using polymerase chain reaction–restriction fragment length polymorphism.
Results: Fifteen and nine β-thalassemia major patients displayed SS and Ss genotypes, respectively, whereas 13 were found to have an ss genotype. The mean BMD of the β-thalassemia major patients with ss genotype was similar to those with the Ss and SS genotypes. In the control group, 77 and 15 subjects had SS and Ss genotypes, respectively, with no ss genotype. Allelic and genotypic distribution in patients were significantly different from controls.
Conclusion: Determining base substitutions at the Sp1 binding site on the COLIA1 gene in early years may be important in preventing osteoporosis in children with β-thalassemia major.     

Bovine β-Lactoglobulin in the Human Milk

ABSTRACT. Human milk samples ( n =232) collected during the whole lactation period from 25 healthy, Swedish mothers were analyzed by radioimmunologic method for content of bovine β-lacto-globulin. Detectable amounts (5-800 μ/1) were found in 93 of 232 milk samples (40%). Six mothers had no detectable β-lactoglobulin in their breast milk on any occasion. Two mothers had measurable /Mactoglobulin in all their milk samples. No correlation was found between daily cow's milk intake and concentration of β-lactoglobulin in the milk samples. Six mothers with allergic symptoms such as asthma, hay-fever, eczema all had detectable amounts of β-lactoglobulin in their milk. Of 19 mothers without allergy, 13 had detectable amounts. This difference did not show statistical significance. The presence of symptoms in the infant such as diarrhoea, vomiting, colic, exanthema was significantly correlated to high levels of β-lactoglobulin in the milk. Bovine β-lactoglobulin was also detected in 7 of 13 serum samples. The two mothers with detectable β-lactoglobulin in all milk samples had the highest serum values, and their infants suffered from gastro-intestinal symptoms, weight decline and exanthema.     

Values for urinary β-microglobulin and N-acetyl-β-D-glucosaminidase in normal healthy infants

Abstract Background : Measuring urinary β₂ microglobin (B2M) and N -acetyl-β-D-glucosaminidase (NAG) excretion is widely used as a valuable clinical tool in assessing renal tubular lesions. However, few data are available on normal values for urinary excretion of B2M and NAG in infancy.
Methods : Urinary B2M and NAG were measured in healthy infants. The logarithmic values of urinary B2M, NAG. B2M/creatinine ratio and NAG/creatinine ratio were distributed almost normally and reference ranges were calculated from the logarithms of the observed values.
Results : The levels of urinary B2M and B2M/creatinine ratio were highest in the 1-month-old group, followed by a decrease during the first 3 months. Urinary B2M excretions in the 3-monfh-old group showed rather lower levels than those of the 12-month-old and 36-month-old groups. Although urinary NAG excretions were almost constant throughout all groups, urinary NAG/creatinine ratio decreased gradually until 3 years of age.
Conclusions : We suggest that these reference ranges are of importance in evaluating tubular damage due to a variety of renal diseases in infancy.     

Is homozygous α-thalassaemia a lethal condition in the 1990s?

Two cases of homozygous α-thalassaemia who received active treatment in accordance with parental wishes are reported. One infant survived and the other, although successfully weaned off mechanical respiratory support, unexpectedly developed portal vein thrombosis and died. Homozygous a-thalassaemia, a condition previously considered to be universally fatal, and an indication for therapeutic abortion, is now potentially curable with advances in diagnostic technology and treatment. However, active management of these cases raises serious ethical questions and has major financial implications on the health-care system. Invasive prenatal and intensive postnatal interventions should remain experimental and cannot be recommended as routine clinical practice until the questions of long-term neurodevelopmental outcome, and the morbidity and mortality associated with bone-marrow transplantation have been fully addressed. As a result of advances in information technology, more and more parents of affected foetuses are likely to request active treatment.     

αβ and γδ T cell subsets in chronic renal failure in children on dialysis treatment

BACKGROUND: Impaired immunity, particularly cell-mediated, is one of the features of chronic renal failure. This also concerns impaired T cell dependent responsiveness. METHODS: The expression of T cell surface antigens (CD3, CD25, TCRalphabeta, TCRgammadelta) was evaluated on peripheral blood (PB) mononuclear cells using two-color flow cytometry in 10 children on continuous ambulatory peritoneal dialysis (CAPD) and in 13 children on maintenance hemodialysis (HD) with polysulfone and cuprophane dialysers. RESULTS: In HD children absolute numbers of leukocytes, lymphocytes, CD3+, alphabeta, gammadelta T cells and a percentage of gammadelta T cells were decreased versus healthy children. Also, we observed a relative increase of CD3+, CD3+/CD25+ and alphabeta T cells after sessions with cuprophane membranes, and an increase of CD3+/CD25+, alphabeta T cell percentages after sessions with the polysulfone membranes. Additionally we found a decrease of both relative and absolute numbers of gammadelta T cells after HD with polysulfone. In CAPD children we found declined absolute numbers of total lymphocytes, CD3+ and alphabeta T cells and higher relative values of CD3+ and alphabeta T cells versus controls. CONCLUSIONS: The T cell depletion in chronic renal failure (CRF) patients primarily results from uremic-related toxicities, rather than from CAPD or HD-related incompatibilities. We showed a significant decrease of gammadelta T cells in CRF patients on HD, that may be partly responsible for impaired T-dependent responsiveness in that group. The intradialytic changes of gammadelta Tcells may result from a different degree of biocompatibility during the application of various dialysis membranes.     

Body proportions in Turner's syndrome.

Body proportion was studied in Turner''s syndrome by measurement of standing an sitting heights in relation to chronological and bone age. The mean standard deviation score for standing height was -3.8. Disproportionate growth of the legs was not a major determinant of short stature, either before or after oestrogen replacement.     

Body proportions in fanconi anemia heterozygotes

To study the anthropometric ratios in parents (heterozygotes) of children withFanconi anemia. The study was carried out in the Department of Hematology, Institute of Child Health & Hospital for Children, Chennai. Parents of children with Fanconi anemia were the subjects of the study. Applying standard instruments and methods, various body measurements were recorded. 31 fathers and 37 mothers were included in the study. A hundred male and female controls of the same ethnic group were also studied for the same parameters. The ratios were calculated and statistically analyzed. It was observed that fathers (male heterozygotes) had shorter forearms, the ratio of upper arm: forearm was significantly increased compared to male controls. In mothers (female heterozygotes) the inter-pupillary distance was increased, the ratio of head circumference to inter-pupillary distance was decreased compared to female controls.     

Mucolipidosis with β-Galactosidase Deficiency: a Type of Sialidosis

Sialidosis is characterized by the Hurler-like clinical pictures, progressive neurodegenerative course and an increase in sialic acid-rich saccharides in urine. However, it looks a heterogenous category consisted of several clinical disorders. Recently it has been established that acid neuraminidase is deficient primarily in this disease. We reviewed sialidosis and discussed biochemical characteristics including coexisting β-galactosidase abnormality.     

Human milk components cross-reacting with antibodies against bovine β-lactoglobulin

The human whey components cross-reacting with antibodies raised against bovine and/or equine beta-lactoglobulin were screened systematically. The milk of six women on a normal diet was collected within 72 h of confinement and whey components were fractionated by high-speed size exclusion chromatography and reversed-phase techniques. The fractions which were immunoreactive in double diffusion experiments with antisera anti-bovine and/or equine beta-lactoglobulin were subsequently purified by native PAGE and then electroblotted on Pro-blott membrane (Western blotting). Pro-blot membranes were stained in parallel with Coomassie and by immunostaining using antibodies against bovine and/or equine beta-lactoglobulin as first antibody solution. The immunoreactive bands were cut out from the membrane and N-terminally sequenced; all the immunoreactive components were clearly identified as human beta-casein or its (mainly tryptic) fragments. The strong antigenic similarity between human beta-casein and beta-lactoglobulin (bovine and equine) might be of immunological importance; it could mean that breast-fed neonates risk being sensitized to beta-lactoglobulin irrespective of the presence of cow's milk in the mother's diet.     

Coexisting Hereditary Methaemoglobinaemia and Heterozygous β-Tialassaemia

ABSTRACT. Cyanosis was noted within a few weeks after birth in two sisters. On investigation the cause of cyanosis was found to be congenital methaemoglobinaemia due to NADH diaphorase deficiency. Heterozygous β-thaiassaemia was present as an additional incidental finding in one of the sisters, but did not contribute to the symptoms, thus showing that the two diseases, when coexistent, do not pose additional haematological problems. However, it is possible that the β-thalassaemia counteracts the tendency to compensatory erythrocytosis induced by methaemoglobinaemia