No abstract

The population of this region is conscious and willing to accept prenatal diagnosis as a means of control of thalassemia.

Incidence of a-thalassaemia in the urban population of India, estimated by the presence of Hb Bart's in cord blood, ranges between 0AE5 and 18AE0% depending on the technique used for screening (Hassall et al, 1998). The molecular nature of the lesions causing alpha-thalassaemia in patients belonging to different geographical and ethnic backgrounds in the heterogeneous population of India has not been documented in detail, except in isolated studies on expatriates. One recent study describes a 0 deletions in Indian alpha-thalassaemia patients (Shaji et al, 2003 Case reportAn anomalous fragment of c. 500 bp length was reproducibly obtained (Fig 1A) in three individuals. The haematological parameters of these three probands are presented in Table Ia SummaryWe have detected, in three unrelated eastern Indian individuals, a hitherto unreported alpha zero deletion, --KOL, in the heterozygous state, encompassing the embryonic zeta2-globin and the duplicated alpha-globin genes extending from c. 1150 bp upstream of the zeta2 globin gene to c. 960 bp downstream of the theta1 gene. Other deletions present in 120 unrelated, eastern Indian, putative alpha-thalassaemia patients are )3AE7 kb (16AE25%), )4AE2 kb (5%) and --SEA (3AE33%).

SummaryHaemoglobin (Hb) Sun Prairie (a2-globin cd130, GCT fi CCT, Ala fi Pro) is detected in three unrelated chromosomes, in association with a C fi T transition in the 5¢-untranslated region (UTR), two bases upstream from the translation start site. Reported inversion of a/b-mRNA ratio observed in Hb Sun Prairie mutants might stem from the second mutation and should be investigated. Molecular modelling studies indicate that the 130th residue of a-globin faces primarily the central cavity of the molecule and is not in contact with any b-chain residue; further, no significant disruption of the Hb structure because of the Sun Prairie mutation is discernible. Depression of translation because of the second mutation of a conserved base in the 5¢-UTR might explain the observed clinical severity.

Growth and pubertal disturbances are the most common causes of morbidity, affecting 60-80% β-thalassemia major (β-TM) patients worldwide, due mainly to hypogonadotrophic hypogonadism (HH). We undertook a 6-year prospective study of 55 Indian β-TM children with stunted growth and absent or arrested puberty, aged 15-18 years with pulsatile HH, to evaluate the role of low dose sex steroid priming (6-12 months) for physiological induction of puberty. Eighty percent responded favorably with increase in height, growth spurt and completed pubertal maturation [Tanner stage 4-5 (T4-T5)] and 20% moved from T2 to T3. There was biochemical improvement in maturation of hypothalamic-pituitary (H-P) axis. Those younger than 15 years with minimal iron load had the best outcome. Our data suggest that sex steroid priming is a feasible method of induction of physiological puberty in β-TM patients with sexual infantilism and reversible apulsatile HH, especially in younger patients with minimal iron loads.