The rare hemoglobin variant Hb Mizuho: report of a Swiss family and literature review

Abstract

Hb Mizuho is a very rare unstable hemoglobin; here, we describe the clinical history of three Swiss family members with Hb Mizuho together with a systematic review of the previously six published cases. The clinical history of the adult woman we report here is unique since this is the first Hb Mizuho presenting with Moyamoya complications and the first case reported with long-term erythrocyte exchange. The literature review showed that Hb Mizuho was mainly reported as a de novo mutation, with the exception of children descended from known cases. All published patients with this unstable hemoglobin showed severe hemolytic anemia with the exception of one; all were regularly transfused. Patients with higher HbF levels might require fewer transfusions. All patients underwent splenectomy at a median age of 4 years and had variable clinical improvement; some achieved complete resolution of transfusion dependency after splenectomy. Iron overload in Hb Mizuho patients seems to be mainly attributed to transfusions and has less to do with ineffective erythropoiesis. Diagnosis might be challenging; a normal hemoglobin electrophoresis should not rule out the diagnosis of unstable hemoglobin in patients with otherwise unexplained hemolytic anemia. This series shows the enormous utility of using molecular techniques for diagnosis.

Extreme Reticulocytosis After Splenectomy in a Patient With Hemoglobin Mizuho

“…11 Our patient underwent splenectomy at 4 years of age, and the transfusion-dependency decreased markedly thereafter. This corresponds well with the outcomes of splenectomy in other patients with Hb Mizuho, where 5 of 10 previous cases had a persistent but decreased need for blood transfusions postsplenectomy, 6 3 cases did not require transfusions after being splenectomized and 1 case had not been transfusion-dependent before splenectomy. 3 In one case, it was not reported whether the patient had undergone splenectomy.…”

“…It is well known that removal of the spleen prolongs the lifespan of RBCs by reducing sequestration, 6 and a significant sustained decrease in annual blood transfusion requirements have been found postsplenectomy in patients with β-thalassemia. 11 Our patient underwent splenectomy at 4 years of age, and the transfusion-dependency decreased markedly thereafter.…”

“…9 Splenectomy has previously been shown to decrease reticulocyte count in children with congenital hemolytic anemia. 10 Reticulocytosis has been described in some patients with Hb Mizuho before splenectomy, [2][3][4]6,7 and in others after splenectomy. 2,5,6 Here, we present the case of a young boy with Hb Mizuho who developed a dramatically elevated reticulocyte count after splenectomy.…”

“…Hemoglobin (Hb) Mizuho is a rare, autosomal dominant hemoglobinopathy reported in only 10 cases worldwide 1–7 . The condition is caused by a mutation in the β-globin gene with a Leu → Pro substitution ( HBB : c.206T>C), resulting in a very unstable Hb 1 .…”

“…The condition is caused by a mutation in the β-globin gene with a Leu → Pro substitution ( HBB : c.206T>C), resulting in a very unstable Hb 1 . It occurs predominantly as a de novo mutation, with only 2 cases known to have passed the condition to their children 5,6 . Hb Mizuho is clinically characterized by severe, transfusion-dependent hemolytic anemia, and patients are usually splenectomized during childhood, which decreases—and in some cases, eliminates—the need for blood transfusions 6 …”