What are hemoglobinopathies?

Hemoglobinopathies (HbP’s) are diseases of the hemoglobin molecule. They are the world’s most common mono-genic, autosomal, and recessive disease in man.

What is a mono-genic, autosomal, recessive disease?

The about 25,000 genes, which make our genetic blueprint, are located on our 46 chromosomes. 44 chromosomes come in pairs (22 from the mother and 22 from the father) and are named autosomes. The two remaining chromosomes XX or XY (or sex chromosomes) are inherited as follows: Mothers who have two X-chromosomes can only give one of both. Fathers may give either their X-chromosome and then the child will be a daughter (with two X-chromosomes like the mother) or their Y chromosome and then the child will be a son (with an X and an Y chromosome like the father). Thus a mono-genic, autosomal, recessive disease is a disease caused by a mutation on a single gene (mono-gene) which is located on one of the 44 autosomes and which does not manifest in the carrier (recessive). Why recessive? Because the presence of the equivalent gene without the mutation on the other autosome is sufficient to prevent the expression of the mutation (a disease in the case of hemoglobinopathy) in the carrier. In other words carriers (heterozygotes) of mono-genic, autosomal, recessive diseases do not manifest the disease which is eventually associated with the mutation.

Why there are so many carriers of HbP worldwide?

Because HbP carriers are protected in childhood from the fatal consequences of malaria tropica, and thus selectively advantaged. This selection mechanism has increased the number of HbP carriers to, on average, 5% of the world population. However, healthy parents who are both carriers of HbP may give their children both genes carrying the defect (Click here for information about hereditary risk). These children are then homozygous or compound heterozygous for a HbP mutation. Without the compensation of a normal gene to protect them, they will be affected by an incurable hemolytic anemia. Worldwide, 350,000 severely affected children are born from healthy carrier parents each year.

General consideration

Hemoglobinopathies become more common in formerly non-endemic countries as a consequence of migration. As the population changes hemoglobinopathies may become a serious health problem to societies formerly unaware of the existence of sickle cell disease and thalassemia intermedia/major. It is therefore recommended to anticipate on the growing number of young carriers, who otherwise remain undiagnosed. Being unaware of their carrier status they have 25% chance as a carrier couple to be confronted with a severely affected child.

Prevention of HbP’s

Frequent homozygous or compound heterozygous forms of HbP are called β-thalassemia major and sickle cell disease (SCD). These diseases manifest soon after birth and can be extremely severe. Although a few cases may undergo a successful bone marrow transplant, these patients remain incurable and can only be intensively treated by lifelong supportive therapy. Successful prevention strategies have been applied in several countries with high HbP carrier frequencies. To date, the problem of prevention of HbP major has made an entrance in the immigration countries of Northern Europe where large sections of the population are at risk for severe HbP in their progeny because of their high carrier frequency, endogamy (interfamily marriages) and higher reproductive rates.