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Objective: To investigate the role of haematological indices, socioeconomic status, and morbidity in prepubertal growth in homozygous sickle cell (SS) disease.Method: Height, weight, and haematology were serially recorded in a cohort study of 315 children with SS disease from birth to 9 years at the sickle cell clinic of the University Hospital of the West Indies, Kingston, Jamaica.Results: Height increment between 3 and 9 years correlated positively with total haemoglobin at age 7 years in boys but not girls. Attained height and weight at age 7 years correlated positively with haemoglobin and fetal haemoglobin in boys but not girls. Only the correlation between haemoglobin and weight showed a significant gender difference. Partial correlation analysis suggested that the effect of haemoglobin was accounted for by the effect of fetal haemolglobin and further analysis indicated that height correlated with F reticulocyte count (a measure of fetal haemoglobin production) in both sexes but not with the ratio of F cells to F reticulocytes (a measure of F cell enrichment). Growth was not significantly related to mean red cell volume, proportional reticulocyte count, alpha thalassaemia, socioeconomic status, or morbidity.Conclusion: A high concentration of fetal haemoglobin in boys with SS disease is associated with greater linear growth. It is postulated that in boys, low concentrations of fetal haemoglobin increase haemolysis and hence metabolic requirements for erythropoiesis, putting them at greater risk of poor growth. Differences in the relationship of haematology and growth between boys and girls with SS disease dictate that future analyses of growth take gender into account. [ABSTRACT FROM AUTHOR]

The frequencies of four malaria associated erythrocyte genetic abnormalities have been established in 1000 Omani subjects. They are: homozygous alpha+ thalassaemia (-alpha/-alpha) 0.45; high Hb A2 beta thalassaemia trait 0.015; sickle trait (Hb A/S) 0.061; and glucose 6 phosphate dehydrogenase deficiency (Gd-): males 0.27, females 0.11. From our data the alpha+ (-alpha/) thal gene (confirmed by Southern blotting) is pandemic in this population. Moreover, in spite of the very high frequency of Gd-, oxidative haemolytic syndromes are very uncommon. Also preliminary data indicate that among the Omani population with sickle cell disease, homozygosity of the alpha+ gene markedly modifies the clinical picture. [ABSTRACT FROM PUBLISHER]

It has previously been suggested that the non-deletion form of the alpha thalassaemia/mental retardation syndrome may be an X linked disorder. We describe four brothers with this syndrome in whom the diagnosis was first suspected because of their characteristic clinical features, although these varied somewhat from one sib to another. The diagnosis was confirmed in each case by showing Hb H inclusions in a proportion of their red blood cells. The identification of four similarly affected boys in this pedigree is consistent with an X linked pattern of inheritance. In support of this, very rare Hb H inclusions could be found in the red blood cells of the mother and one sister who both share some facial features with the affected boys and are presumably carriers of this disorder. This pedigree thus provides further evidence that this is an X linked syndrome and indicates the clinical and haematological variability that may exist even within a single affected family. [ABSTRACT FROM PUBLISHER]

We describe three males (two brothers and a cousin) who have the X linked alpha thalassaemia/mental retardation (ATR-X) syndrome. The diagnosis, originally suspected in the brothers because of similarity in dysmorphic features to previous cases, was confirmed haematologically in the surviving brother. The cousin has less typical dysmorphism and a virtually normal routine blood count, but haemoglobin H inclusions were found in his red blood cells showing that he has the same condition. This report expands the clinical phenotype of the ATR-X syndrome and emphasises that a normal blood count does not exclude the diagnosis. [ABSTRACT FROM PUBLISHER]

A combination of polymorphic DNA markers, cytogenetic analysis, and in situ hybridisation has been used for the high resolution assignment of the human alpha globin gene cluster on chromosome 16. Multiallelic DNA probes from within the alpha globin cluster were used to determine the number of copies of this locus in three cell lines containing trisomies of the short arm of chromosome 16 and one with a familial inversion, inv(16). The breakpoints in these rearrangements flank the alpha globin locus and locate a shortest region of overlap to 16p13.1. A meiotic crossover was also localised to this band. In situ hybridisation of biotinylated DNA probes to normal and inverted chromosomes 16 [inv(16)(p13.1;q22)] showed hybridisation sites at opposite ends of the chromosomes, consistent with this regional localisation. [ABSTRACT FROM PUBLISHER]

This report describes a Negro family with the G gamma beta + type of hereditary persistence of fetal haemoglobin. Family members with levels of haemoglobin F of 17 to 23% had normal red cell indices, balanced globin chain synthesis, and a pancellular distribution of the fetal haemoglobin, showing that these subjects have a form of HPFH. The production of Hb A and C in addition to the large amount of Hb F in one family member showed that there was an active beta A gene in cis to the HPFH determinant, while structural analysis of the Hb F revealed the presence of only G gamma chains. The criteria for the diagnosis of G gamma beta + HPFH, and the relevance of such conditions to the control of globin gene expression, are discussed. [ABSTRACT FROM PUBLISHER]

The interaction of homozygous alpha thalassaemia 2 with homozygous sickle cell (SS) disease results in a generally milder haematological picture with less intravascular sickling, less haemolysis, and higher haemoglobin levels. Clinically, patients are generally more mildly affected, though not all vaso-occlusive complications are reduced. Thus there is a possibility that the advantages gained by inhibition of sickling have been offset by the rheological disadvantages of the higher haemoglobin level. The capillary bed in the perimacular region of the posterior pole has been used to examine the degree of vaso-occlusion in age and sex matched controls with SS disease with and without homozygous alpha thalassaemia 2. The results demonstrated significantly less capillary abnormalities in the perimacular region of patients with alpha thalassaemia, though the size of the foveal avascular zone and the grading of perimacular capillary drop-out did not differ between the 2 genotypes. These results are compatible with a mild inhibitory effect of alpha thalassaemia on vaso-occlusion of the macular vasculature in SS disease. [ABSTRACT FROM PUBLISHER]

A female child with alpha thalassaemia trait, moderate mental retardation, and dysmorphic features has inherited an abnormal chromosome 16 complement as a result of the unbalanced segregation of a maternal balanced translocation. Cytogenetic analysis indicates that the patient is monosomic for 16p13.3----pter and trisomic for 10q26.13----qter. DNA studies show that the patient has not inherited either maternal alpha globin allele. This accounts for the alpha thalassaemia trait in the child and places the human alpha globin complex in band 16p13.3----pter. [ABSTRACT FROM PUBLISHER]

A novel form of severe, X linked mental retardation associated with alpha thalassaemia (ATR-X syndrome) has recently been described. Two affected cousins are described, one of whom has an unusually mild haematological phenotype. HbH inclusions, which are the hallmark of this disease, were only detected in the peripheral red blood cells after repeated observations. [ABSTRACT FROM AUTHOR]

Homozygous alpha+ thalassaemia (alpha-/alpha-) ameliorates some of the clinical manifestations of homozygous sickle cell (SS) disease but its effect on retinal complications remains unknown. This has been assessed by visual examination and fluorescein angiography in 39 subjects with SS disease and homozygous alpha+ thalassaemia and in 39 age/sex matched controls with SS disease but with a normal alpha globin genotype (alpha alpha/alpha alpha). The results indicate that homozygous alpha+ thalassaemia reduces the extent of peripheral retinal vessel closure but has no apparent effect on the frequency of proliferative sickle retinopathy. [ABSTRACT FROM PUBLISHER]

Presents an abstract of the article "SW-ARRAY: A Dynamic Programming Solution for the Identification of Copy Number Changes in Genomic DNA Using Array Comparative Genome Hybridization Data," by Tom Price, R. Regan, R. Mott, A. Hedman, B. Honey, R. J. Daniels, L. Smith, A. Greenfield, A. Tiganescu, V. Buckle, H. Ayyub, J. Ragoussis, D. R. Higgins, J. Flint and S. J. L. Knight.

Objectives: To determine the effect of arthroscopic capsular shift surgery on pain and functional impairment for people with atraumatic shoulder (glenohumeral) joint instability., Methods: We conducted a randomised, placebo-controlled clinical trial in a specialist secondary care facility. Patients aged 18 years and over who reported insecurity (apprehension) in their shoulder joint and had evidence of capsulolabral damage on arthroscopic examination were included. Patients were excluded if their shoulder apprehension symptoms were precipitated by a high velocity shoulder injury, they had bony or neural damage, a rotator cuff or labral tear, or previous surgery on the symptomatic shoulder. Sixty-eight participants were randomised and received diagnostic arthroscopy, followed by arthroscopic capsular shift or diagnostic arthroscopy alone. All participants received the same postoperative clinical care. The primary outcome was pain and functional impairment measured with the Western Ontario Shoulder Instability Index. The prespecified minimum clinically important effect was a reduction in pain and disability of 10.4 points., Results: Mean reductions in pain and functional impairment for both groups were similar. Compared with diagnostic arthroscopy, arthroscopic capsular shift increased pain and functional impairment by means of 5 points (95% CI -6 to 16 points) at 6 months, 1 point (95% CI -11 to 13 points) at 12 months and 2 points (95% CI -12 to 17 points) at 24 months., Conclusions: Compared with diagnostic arthroscopy alone, arthroscopic capsular shift confers, at best, only minimal clinically important benefit in the medium term., Trial Registration Number: NCT01751490., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)