What is hemoglobin D trait?

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Hemoglobin D Trait

Hemoglobin D trait (heterozygous Hb D-Punjab) is a clinically benign condition that produces no symptoms or hematological abnormalities in carriers, requiring no treatment or monitoring. 1, 2

Genetic Basis and Nomenclature

  • Hemoglobin D-Punjab (also called Hemoglobin D-Los Angeles) results from a point mutation in the beta-globin gene (HBB: c.364G>C) at codon 121, replacing glutamic acid with glutamine (Glu→Gln). 3, 2
  • The variant originated in the Punjab region of Northwestern India and is now one of the most common hemoglobin variants worldwide. 2
  • In Brazil, Hb D-Punjab is the third most common hemoglobin variant, and in India the prevalence is approximately 0.06%. 3, 2

Clinical Presentation of Heterozygous State

  • Individuals with heterozygous Hb D trait (one normal beta-globin gene and one Hb D gene) are completely asymptomatic with normal hematological parameters. 3, 2, 4
  • Red blood cell indices, hemoglobin levels, and complete blood counts remain within normal limits. 4
  • No clinical intervention, treatment, or special monitoring is required for simple heterozygous carriers. 2, 4

Compound Heterozygous States (Clinical Significance)

The clinical picture changes dramatically when Hb D-Punjab is co-inherited with other hemoglobinopathies:

Hb D/Beta-Thalassemia

  • Co-inheritance with beta-thalassemia mutations (particularly IVS-1-5 or IVS-II-1 mutations) produces clinically significant disease resembling thalassemia intermedia with moderate severity. 4, 5, 6
  • Patients present with severe anemia, splenomegaly, hypochromia, microcytosis, and may require transfusions. 4, 5
  • Hemoglobin F levels are moderately elevated (3-4%). 6

Hb S/D-Punjab

  • The most clinically important association occurs with Hb S, producing manifestations similar to homozygous sickle cell disease (HbSS). 1, 2, 4
  • This compound heterozygous state can cause vaso-occlusive crises and hemolytic anemia comparable to sickle cell disease. 2

Hb D/Alpha-Thalassemia

  • Co-inheritance with alpha-thalassemia deletions (such as the 3.7 kb deletion) produces variable clinical presentations. 3, 4

Homozygous Hb D-Punjab

  • Homozygosity for Hb D-Punjab is rare and generally benign. 6
  • May produce mild hemolytic anemia and mild to moderate splenomegaly in some cases. 3, 4
  • Most homozygous individuals remain asymptomatic. 6

Diagnostic Approach

  • High-performance liquid chromatography (HPLC) is the primary screening method but may not distinguish all compound heterozygous states reliably. 4
  • Hemoglobin electrophoresis at alkaline pH can identify Hb D variants. 5
  • Molecular DNA analysis (sequencing, Gap-PCR for alpha deletions, ARMS for beta mutations) is essential for definitive diagnosis when patients are symptomatic or when compound heterozygous states are suspected. 4, 6
  • Complete blood count with red cell indices should be obtained in all suspected cases. 4

Genetic Counseling Implications

  • Heterozygous carriers should receive genetic counseling regarding the risk of passing the variant to offspring, particularly if their partner carries Hb S, beta-thalassemia, or other hemoglobinopathies. 1, 2
  • Consanguineous marriages increase the risk of compound heterozygous or homozygous states. 5
  • Family screening is recommended when Hb D-Punjab is identified, especially in populations from Northwestern India where prevalence is higher. 2, 4

Key Clinical Pitfall

The critical error is assuming all Hb D carriers are asymptomatic—always investigate for co-inherited hemoglobinopathies (particularly beta-thalassemia or Hb S) in any patient with Hb D who presents with anemia, splenomegaly, or other hematological abnormalities. 4, 5

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

2
Research

Hemoglobin D-Punjab: origin, distribution and laboratory diagnosis.

Revista brasileira de hematologia e hemoterapia, 2015

5
Research

Co-Inheritance of Haemoglobin D-Punjab and Beta Thalassemia - A Rare Variant.

Journal of clinical and diagnostic research : JCDR, 2017

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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