A thalassemia with hydros fetalis, complete lack of a-globin, excess y-globin does not release oxygen, fetal demise.

A thalassemia with hydros fetalis, complete lack of a-globin, excess y-globin does not release oxygen, fetal demise.

• A. Four defective genes
• B. One defective gene
• C. Two defective genes
• D. Three defective genes

Answer: (A)

Alpha-thalassemia severity depends on how many alpha-globin genes are deleted. There are four alpha-globin genes in total (two on each chromosome 16). If all four are deleted, the fetus cannot produce alpha-globin chains, so gamma-globin is produced in excess. These gamma-globin tetramers form Hb Bart’s (gamma4), which has very high oxygen affinity and cannot release oxygen to fetal tissues. The resulting severe hypoxia leads to hydrops fetalis and usually fetal demise in utero. Thus the described scenario—no alpha-globin, excess gamma-globin that fails to deliver oxygen, fetal death—is best explained by deletions of all four alpha-globin genes.

Alpha-thalassemia severity depends on how many alpha-globin genes are deleted. There are four alpha-globin genes in total (two on each chromosome 16). If all four are deleted, the fetus cannot produce alpha-globin chains, so gamma-globin is produced in excess. These gamma-globin tetramers form Hb Bart’s (gamma4), which has very high oxygen affinity and cannot release oxygen to fetal tissues. The resulting severe hypoxia leads to hydrops fetalis and usually fetal demise in utero.

Thus the described scenario—no alpha-globin, excess gamma-globin that fails to deliver oxygen, fetal death—is best explained by deletions of all four alpha-globin genes.