Vascular-type disruptive defects in fetuses with homozygous alpha-thalassemia: report of two cases and review of the literature

Prenat Diagn. 2005 Dec;25(12):1088-96. doi: 10.1002/pd.1276.

Abstract

Background: The thalassemias are an inherited group of heterogeneous anemias in which one or more of the globin chains in the hemoglobin tetramer are absent. Fetuses with homozygous alpha-thalassemia, which is particularly prevalent in people of Southeast Asian extraction, experience deficient alpha-globin chain synthesis and cannot produce hemoglobin F (the primary fetal hemoglobin after 8 weeks' gestation). Instead, they produce an anomalous hemoglobin, hemoglobin Bart's, with an unusually high affinity for oxygen, leading to profound anemia and tissue hypoxia.

Methods and results: Here we report on two fetuses with homozygous alpha-thalassemia who displayed structural defects of a vascular disruptive type. Both fetuses demonstrated limb anomalies, including terminal transverse limb deficiencies, and one fetus was found to have a brain malformation consisting of a neuronal migrational defect. The limb anomalies and suspected brain malformation were detected on prenatal ultrasound prior to confirmation of the diagnosis of alpha-thalassemia in one case; in the other case prenatal records were not available. While microcephaly, hydrocephalus, and retarded brain growth have been rarely reported in association with homozygous alpha-thalassemia, this is the first report of a true brain malformation in an affected fetus. Limb anomalies, on the other hand, appear to be more frequent. Recently, aggressive in utero and postnatal therapies for homozygous alpha-thalassemia have been attempted with some success.

Conclusions: Our cases and those from the medical literature suggest that couples need to be counseled about the risks of congenital anomalies of a vascular disruptive type in affected fetuses. Furthermore, data from the literature suggests that in utero therapy may not significantly decrease these risks as such anomalies may be present prior to the institution of therapy. In addition, in hydropic infants with vascular disruptive defects, especially in those of Southeast Asian origin, homozygous alpha-thalassemia should be suspected as a likely etiology.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Brain / abnormalities*
  • Brain / embryology
  • Female
  • Fetus / blood supply*
  • Gestational Age
  • Homozygote
  • Humans
  • Hydrops Fetalis / etiology
  • Hydrops Fetalis / genetics
  • Hydrops Fetalis / pathology
  • Limb Deformities, Congenital / diagnostic imaging
  • Limb Deformities, Congenital / embryology
  • Limb Deformities, Congenital / genetics*
  • Pregnancy
  • Prenatal Diagnosis
  • Ultrasonography, Prenatal
  • alpha-Thalassemia / complications
  • alpha-Thalassemia / diagnosis*
  • alpha-Thalassemia / genetics