Alpha thalassemia major—new mutations, intrauterine management, and outcomes

Abstract

Alpha thalassemia disorders are a group of hereditary anemias caused by absent or decreased production of the alpha chain of hemoglobin. Hemoglobin Bart’s hydrops fetalis is usually a fatal in-utero disease caused by absence of the alpha genes. However, the molecular and genotypic expression of hemoglobin Bart’s varies and increasing numbers of births are being reported. Population screening and prenatal diagnosis of at-risk couples is essential but often not performed. Most affected pregnancies are often undetected, resulting in severe fetal and maternal complications. Noninvasive monitoring by Doppler ultrasonagraphy with intrauterine transfusion therapy has changed the prognosis for this disorder. These advances in intrauterine and postnatal therapy have resulted in ethical dilemmas for the family and the provider.

The α-Thalassemias

“…Meanwhile, attempts at intrauterine and postnatal therapy are associated with numerous ethical challenges. 29 The homozygous state of α + -thalassemia and the heterozygous state of α 0 -thalassemia (grouped under the term "α-thalassemia minor") are associated with a substantial reduction in the mean corpuscular volume and mean corpuscular hemoglobin. In α + -thalassemia heterozygotes, the mean corpuscular volume and mean corpuscular hemoglobin are usually reduced, but there is a small overlap with normal values.…”

An investigation of the protective effect of alpha+‐thalassaemia against severe Plasmodium falciparum amongst children in Kumasi, Ghana

“…Haemoglobin Koya Dora, another structural non-deletional mutation, is found in India. Other structural mutations such as haemoglobin Quong Sze found in Southeast Asia are highly unstable and result in defect in the haem pocket (Vichinsky, 2009). …”

“…Southeast Asians who are carriers of Haemoglobin Constant Spring, the prevalence is about 8% (Vichinsky, 2009). In the Middle East, the common alpha thalassaemia non-deletional mutation is Haemoglobin  TSaudi .…”

Transfusion Dependent Homozygous α-Thalassemia in Patients Associated with Hypospadias in Three Survivors

“…Due to severe ineffective erythropoiesis, hydropic fetuses have massive organomegaly, severe albuminemia, heart failure, body edema, growth failure, and intrauterine demise [1]. High incidences of congenital abnormalities, such as limb defects, hydrocephalus, microcephaly, atrial septal defects, pulmonary hypoplasia, hypospadias, and skeletal dysplasia, have also been reported [2].…”