Hemoglobin C

Snapshot

A 25-year-old immigrant from Nigeria presents to the clinic with complaints of occasional fatigue. He has no other symptoms and denies any unexpected weight loss or night sweats. On exam, he has no lymphadenopathy. He does have mild splenomegaly and some conjunctival pallor. Labs reveal increased MCHC with intracellular crystals seen on blood smear.

Introduction

Hemoglobinopathy with extravascular hemolysis
- hemoglobin C trait (HbAC) with no clinical symptoms
- hemoglobin C disease with mild hemolytic anemia and splenomegaly
Hb C is a structural variant of normal hemoglobin (Hb A)
Genetics
- autosomal recessive of β-Hb chain
- mutation glutamic acid → lysine at position 6
  - recall sickle cell anemia is glutamic acid → valine at same position
Pathogenesis
- Hb C is less soluble and crystalizes
- ↑ blood viscosity
- ↑ cellular rigidity
- shortened red cell survival
Epidemiology
- common in Africa, southern Europe, South America, and Central America
Potentially protects against malaria
If co-inherited with Hb S (structural abnormality seen in sickle cell disease)
- Hb SC is less severe than Hb SS
- vaso-occlusive episodes
- vascular retinopathy
avascular necrosis of femoral head

Presentation

Evaluation

Diagnostic
- hemoglobin electrophoresis or high-performance liquid chromatography
  - mostly Hb C
  - absent Hb A
  - ↑ Hb F (fetal Hb)
↑ MCHC may be noted
Peripheral blood smear
- may show intracellular crystals
- may show target cells
Markers of hemolysis
- ↑ LDH
- ↑ reticulocyte count
↑ indirect bilirubin

Differential Diagnosis

Treatment

Prognosis, Prevention, and Complications

Prognosis
- typically normal
- if co-inherited with hemoglobin S, life expectancy is in the 60s