A case of haemoglobin H (HbH) disease associated with pregnancy is presented and discussed in the light of reports in the literature. The variable symptomatology is commented upon, although mild to moderate chronic haemolytic anaemia seems to be a constant feature. The roles of folic acid supplements and of splenectomy; the avoidance of oxidant drugs, and the mode of inheritance in HbH disease are briefly commented upon. Available reports indicate that HbH disease probably has no adverse effect on pregnancy. However, the association of the two conditions is uncommon, and reports are too few, therefore, to allow definite conclusions on the outcome in all instances.
The clinical spectrum of HbH disease varies from a benign disorder to a severe anemia which is blood-transfusion dependent. Heterogeneity at the clinical level is now being understood in terms of the underlying molecular defects. In this study a mild phenotype found in a group of patients with HbH disease is associated with two types of alpha-thalassemia. These are: alpha+-thalassemia (-alpha 3.7/) and alpha 0-thalassemia (--SEA/). In contrast, a second group with more severe HbH disease has a non-deletional alpha-thalassemia defect instead of alpha+-thalassemia (genotype alpha alpha T/--SEA). In the majority of cases, the basis for non-deletional alpha-thalassemia is Hb Constant Spring.
The hemoglobinopathies include all genetic diseases of hemoglobin (Hb) and fall into two main groups: the thalassemias and structural hemoglobin variants (abnormal hemoglobins). Thalassemia is a public health problem in Malaysia. About 4.5% of the Malays and Chinese are β-thalassemia carriers. We performed hemoglobin analysis on a total of 499 patients from a Government Hospital and Health Clinics in the state of Perlis, Malaysia. About 91.4% of the patients were Malays. All patients had microcytic hypochromic anemia except for a few who went for thalassemia screening. Female patients outnumbered male patients in the ratio of 3.5:1. About 75.7% of the female patients were of childbearing age (17 - 40 years) and a majority of them were there for their antenatal checkup. Using our screen tests (full blood count, high performance liquid chromatography (HPLC), and agarose gel electrophoresis), the common hemoglobinopathies detected were HbE trait (19.3%), β-thalassemia trait (14.6%), HbH disease (1.8%), Hb Constant Spring (1.6%), Homozygous HbE (1.4%), and HbE- β-thalassemia (1.4%). Thalassemia is preventable through screening and education programmes, and prenatal diagnosis. Thalassemia screening is provided free of charge at various government hospitals and health clinics throughout the country.
Key words: Hemoglobinopathies screening, β-thalassemia trait, HbE trait, Thalassemic diseases
Restriction enzyme analysis of the alpha and zeta globin genes was carried out in four cases of Hb Bart's hydrops fetalis, in three patients with Hb H disease without Hb CoSp, in three patients with Hb H disease with Hb CoSp, in 47 individuals with alpha thalassemia trait, and in 47 normal individuals. All four cases of Hb Bart's hydrops fetalis resulted from deletions of alpha 1 and alpha 2 globin genes which did not extend to the psi zeta 1 and zeta 2 globin genes. The same type of deletion was observed in alpha thal1 carriers, but two newborns (one Malay and one of Chinese extraction) had a nondeletion type of alpha thal1 which was confirmed by quantitative alpha globin gene analysis. In addition, two other newborns diagnosed as alpha thal1 trait carriers (one Malay, one Chinese) were shown to have a deletion of both alpha globin genes by quantitative alpha globin gene analysis, but further testing with zeta globin gene probe failed to reveal an abnormal fragment length characteristic of an alpha globin gene deletion. We believe that this last condition is due to a large deletion which includes all alpha globin genes and all zeta globin genes on the same chromosome. On another front, Bgl II restriction analysis of all four Hb Bart's hydrops fetalis cases and the alpha thal1 trait carriers showed a 10.5-kb Bgl II restriction fragment, in the hydrops fetalis as a single band, while in the carriers this 10.5-kb fragment was accompanied by the usual normal 12.5-kb and 11.3-kb fragments. We report that this 10.5-kb fragment, previously thought to be specific for the Southeast Asian alpha thal1 gene deletion, is also common in normal individuals. Nevertheless, digestion with other enzymes can clearly differentiate the alpha thal1 and normal genotypes. We distinguish the findings in the alpha thalassemias from the extensive DNA polymorphism in the region of the alpha and zeta globin genes.
Following complete DNA characterisation patients with Hb H disease were assigned into two groups: deletional (alpha +/alpha o) and non deletional (HbCS/alpha o). Earlier studies have indicated that the group with (HbCS/alpha o) has more severe clinical problems. The serum malonyldialdehyde (MDA) levels, a secondary product of lipid peroxidation were within the normal range, though significantly higher levels of MDA were seen in the non-deletional type of Hb H disease when compared with the deletional type. Markedly low vitamin E levels were also seen in the former group. There were no significant differences in clinical severity may be attributed to an interplay of the accelerated destruction of damaged mature red blood cells secondary to the oxidative denaturation of Hb H and inclusion precipitation; higher levels of Hb H and more inclusion precipitation were seen in the group with (HbCS/alpha o). Low levels of vitamin E in the (HbCS/alpha o) group being due to its consumption in the neutralisation of free radicals formed with the oxidation of globin chains.