Hb lepore/β0-thalassaemia with α+-thalassaemia interactions, a potential diagnostic pitfall

Haemoglobin (Hb) Lepore is a variant Hb consisting of two α-globin and two δβ-globin chains. In a heterozygote, it is associated with clinical findings of thalassaemia minor, but interactions with other haemoglobinopathies can lead to various clinical phenotypes and pose diagnostic challenges. We reported a pair of siblings from a Malay family, who presented with pallor and hepatosplenomegaly at the ages of 21 months and 14 months old. The red cell indices and peripheral blood smears of both patients showed features of thalassaemia intermedia. Other laboratory investigations of the patients showed conflicting results. However, laboratory investigation results of the parents had led to a presumptive diagnosis of compound heterozygote Hb Lepore/β-thalassaemia and co-inheritance α+-thalassaemia (-α3.7). Hb Lepore has rarely been detected in Southeast Asian countries, particularly in Malaysia. These two cases highlight the importance of family studies for accurate diagnosis, hence appropriate clinical management and genetic counseling.

HbA2 levels in normal, beta-thalassaemia and haemoglobin E carriers by capillary electrophoresis

The capillary electrophoresis (CE) is a new system that utilizes the principle of electrokinetic separation of molecules in eight electrolyte buffer-filled silica capillaries. In this study, we established the normal ranges of haemoglobin A2 (HbA2) and haemoglobin F (HbF) levels for normal individuals using this system and also the HbA2 level in beta thalassaemia and haemoglobin E (HbE) individuals.

Hydroxyurea appears beneficial in patients with beta-thalassaemia major and intermedia.

Patients with severe inherited β-globin chain disorders may have milder illness if they produce high levels of fetal hemoglobin (HbF). Hydroxyurea (HU) has been shown to enhance HbF levels in patients with sickle cell disease and may be useful in β-thalassemias. We administered HU to 13 patients with β-thalassemia intermedia or major, including 6 splenectomized patients. The patients received escalating doses (10 to 25 mg/kg/d) of HU for around 2 years (median: 21 months, range: 8 - 55 months). Eleven patients responded with an increase in the pre-transfusion HbF levels, from a base line median of 8.0% (2.5 - 61.3%) to 28.0% (6.6 - 49.2%) and 40.7% (4.8 - 72.3%) at 3 months and 18 months post-HU, respectively. A concomitant increment in median hemoglobin levels was noted at 1, 3 and 18 months of HU therapy. Six of 7 transfusion-dependent patients who had an increment of HbF (one with β-thalassemia major) also had reduced transfusion requirement over the 2-year period of HU therapy. Response to HU was also shown by a reduction in spleen size. Apart from oral ulcers that resolved upon dose reduction of HU, no significant toxicity was noted. We conclude that increased HbF production in β-thalassemia patients, with an improvement in erythropoiesis, can be achieved using HU with minimal toxicity.

Complete molecular characterisation of glucose-6-phosphate dehydrogenase (G6PD) deficiency in a group of Malaysian Chinese neonates

We performed DNA analysis on cord blood samples of 128 Chinese male neonates diagnosed as G6PD deficiency in Hospital Universiti Kebangsaan Malaysia by a combination PCR-restriction enzyme digest technique, Single Stranded Conformation Polymorphism analysis and DNA sequencing. We found 10 different G6PD-deficient mutations exist. The two commonest alleles were G6PD Canton 1376 G>T (42.3%) and Kaiping 1388 G>A (39.4%) followed by G6PD Gaohe 592 G>A (7.0%), Chinese-5 1024 C>T, Nankang 517 T>C (1.5%), Mahidol 487 G>A (1.6%), Chatham 1003 G>T (0.8%), Union 1360 C>T (0.8%), Viangchan 871 G>A (0.8%) and Quing Yang 392 G>T (0.8%). Sixty eight percent (88/125) neonates in this study had neonatal jaundice and 29.7% developed hyperbilirubinemia >250 micromol/l. The incidence of hyperbilirubinemia >250 micromol/l was higher in G6PD Kaiping (43.8%) than G6PD Canton (22%) (p< 0.05). There was no significant difference in the incidence of neonatal jaundice, mean serum bilirubin, mean age for peak serum bilirubin, percentage of babies requiring phototherapy and mean duration of phototherapy between the two major variants. None of the 88 neonates required exchange transfusion. In conclusion we have completely characterized the molecular defects of a group of Chinese G6PD deficiency in Malaysia. The mutation distribution reflects the original genetic pool and limited ethnic admixture with indigenous Malays.