Thalassemia major phenotype caused by HB Zürich‐Albisrieden [α2 59(E8) Gly > Arg (HBA2:C.178G > C)] in a Brazilian child

Abstract

Hemoglobin (Hb) Zürich-Albisrieden (ZA) [α2 59(E8) Gly > Arg; HBA2:c.178G > C] is a rare and highly unstable α-chain variant. A few simple and compound heterozygotes (α α/αα and -/α α, respectively) have been described so far in Switzerland and China. We describe here a case of homozygosity for the Hb ZA mutation (α α/α α) in a Brazilian child with severe congenital hemolytic anemia and ineffective erythropoiesis.

HbH disease due to compound heterozygosity for hemoglobins Zürich‐Albisrieden and Sallanches

“…We read with interest the report of the Brazilian thalassemia major child with hemoglobin (Hb) Zürich‐Albisrieden and would like to share our experience with an Indian case with the same variant but with a thalassemia intermedia presentation, illustrating the clinical heterogeneity of α‐thalassemias.…”

“…Hb Zürich‐Albisrieden was described in 2004 . The only six prior reports are from Switzerland, China, and Brazil . This hyperunstable Hb causes a thalassemia major phenotype in homozygotes (α ZA α/α ZA α), HbH disease in compound heterozygotes (α ZA α/α T α or α ZA α/‐α), and hypochromic microcytosis with mild erythrocytosis in heterozygotes (α ZA α/αα) …”

“…6 The only six prior reports are from Switzerland, China, and Brazil. 1,[6][7][8][9] This hyperunstable Hb causes a thalassemia major phenotype in homozygotes ( ZA / ZA ), HbH disease in compound heterozygotes ( ZA / T or ZA /-), and hypochromic microcytosis with mild erythrocytosis in heterozygotes ( ZA / ). 1,[6][7][8][9] Our patient, in addition to expanding the list of genotypes resulting in HbH disease and being the first reported instance of this rare combination worldwide, also highlights other diagnostically relevant points.…”

“…The inappropriate immunosuppressive therapy due to the single 2+ DCT in a recently transfused patient who may have developed clinically insignificant alloantibodies also highlights the importance of evaluating weak or low‐grade positive DCT results from the perspective of the complete clinical scenario . Unlike unstable β‐globin chain variants, unstable α‐chain variants tend to be symptomatic only in homozygous or compound heterozygous states . Molecular techniques remain the mainstay for definitive typing of HbH disease suspected on HPLC.…”

Severe fetal anemia and hydrops fetalis associated with compound heterozygosity for Hb Zurich-Albisrieden (HBA2:c.178G>C) and Hb Quong Sze (HBA2:c.377T>C)

“…6 Compound heterozygosity for Hb ZA and the Southeast Asian (-- SEA ) deletion has also recently been reported to cause hydrops fetalis, 7 and a Brazilian child with thalassemia major phenotype homozygous for the Hb ZA mutation (ZA/ZA) has also been described. 8 However, there have been no reports of compound heterozygosity for Hb ZA and Hb QS. Here, we report a rare case of severe fetal anemia and hydrops fetalis caused by compound heterozygosity for Hb ZA and Hb QS in a fetus in a Chinese woman.…”