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HbC disease
This condition primarily affects red blood cells, leading to them being more rigid and having a shorter lifespan. It can result in mild anaemia and, in some cases, an enlarged spleen. It is more common in individuals of West African descent.
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Overview
HbC disease is a condition that affects haemoglobin, the protein in red blood cells responsible for carrying oxygen throughout the body. In individuals with HbC disease, a specific change in the HBB gene leads to the production of an altered haemoglobin called haemoglobin C (HbC) [PMID:33678074]. Red blood cells containing HbC tend to be more rigid and have a reduced lifespan compared to normal red blood cells, which can cause them to be removed from circulation more quickly.
The condition is inherited and is relatively common among populations of West African descent. Individuals typically inherit one altered copy of the HBB gene from each parent to develop HbC disease (homozygous HbC). If someone inherits only one altered copy and one normal copy, they have HbC trait and are generally healthy carriers.
Symptoms & clinical features
Individuals with HbC disease often experience mild symptoms, or in some cases, no symptoms at all. The most common feature is mild anaemia, which occurs because red blood cells containing HbC are less efficient and have a shorter lifespan [PMID:20301725]. Symptoms of anaemia can include tiredness, pallor (unusual paleness), and sometimes shortness of breath, particularly during physical activity.
Another common clinical sign is an enlarged spleen, known as splenomegaly. The spleen's role is to filter out old or damaged red blood cells, and in HbC disease, it may work harder to remove the abnormal cells, leading to its enlargement. This enlarged spleen is often detected during a physical examination or imaging, and it rarely causes significant problems.
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Affected organs
The primary organs affected in HbC disease are the red blood cells themselves, which are produced in the bone marrow. The altered haemoglobin C causes changes within these cells. The spleen is also commonly affected, becoming enlarged due to its increased activity in removing the abnormal red blood cells from circulation [PMID:20301725]. Less commonly, individuals may experience gallstones, which can form from the breakdown products of red blood cells.
Risks & severity
HbC disease is generally considered a mild condition, and many individuals may not require specific medical treatment. The severity can vary, but it is typically less severe than other haemoglobin disorders like sickle cell disease. Life expectancy is generally normal [PMID:33678074].
Complications are rare but can include occasional episodes of abdominal pain related to the spleen or the formation of gallstones. The risk of developing severe anaemia is low, and regular blood transfusions are not usually needed. As with any chronic condition, monitoring is important to detect any changes or complications early.
Genetic causes
HbC disease is caused by specific changes in the HBB gene, which provides instructions for making the beta-globin chain, a component of haemoglobin. Normal haemoglobin, called haemoglobin A, consists of two alpha-globin chains and two beta-globin chains. In HbC disease, a single change (a point mutation) in the HBB gene results in the substitution of a glutamic acid for a lysine at position 6 of the beta-globin chain [PMID:20301725].
This genetic alteration leads to the production of haemoglobin C instead of haemoglobin A. Red blood cells containing HbC tend to crystallise under certain conditions, making them more rigid. This rigidity contributes to their shorter lifespan and premature removal from circulation, causing the characteristic features of the condition.
- HBB hemoglobin subunit beta
Inheritance pattern
HbC disease has an autosomal recessive inheritance pattern. This means that an individual must inherit two altered copies of the HBB gene - one from each parent - to develop the condition. If a person inherits only one altered copy and one normal copy, they are considered a carrier (HbC trait) and typically do not show symptoms of HbC disease themselves [PMID:20301725].
When both parents are carriers of the HbC trait, for each pregnancy, there is a 25% chance of their child inheriting two altered copies and having HbC disease, a 50% chance of their child being a carrier, and a 25% chance of their child inheriting two normal copies and not being affected or a carrier.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
Diagnosis of HbC disease usually begins with a full blood count (FBC) which may show mild anaemia and changes in red blood cell size. The definitive diagnosis is made through specific haemoglobin analysis tests, such as haemoglobin electrophoresis or high-performance liquid chromatography (HPLC), which can identify and quantify the presence of haemoglobin C [PMID:20301725].
Genetic testing, specifically sequencing of the HBB gene, can confirm the presence of the characteristic genetic change. In the UK, individuals are often referred for genetic testing via the NHS Genomic Medicine Service (GMS) by their GP or a specialist if HbC disease is suspected. Genetic testing for haemoglobinopathies falls under various R-codes depending on the specific clinical indication, and results are interpreted by clinical geneticists.
Management & lifestyle
As HbC disease is typically mild, many individuals may not require specific medical treatment. Management often focuses on monitoring and addressing any symptoms that may arise. Regular check-ups with a haematologist (a doctor specialising in blood disorders) may be recommended, particularly during childhood, to monitor blood counts and spleen size.
For those experiencing mild anaemia, maintaining a balanced diet is generally advised. Folic acid supplementation may be considered in some cases, as it supports red blood cell production. Pain relief can be provided for any discomfort related to an enlarged spleen. If gallstones develop, surgical removal (cholecystectomy) may be necessary. Genetic counselling is often offered to individuals and families to discuss the inheritance pattern and implications for family planning.
UK care pathway
In the UK, individuals suspected of having or diagnosed with HbC disease are typically managed within the NHS. Initial assessment may be by a GP, who can refer to a haematologist or a clinical genetics service. Diagnostic testing is provided through the NHS Genomic Medicine Service (GMS), following established pathways for inherited blood disorders. Genetic counsellors are available to provide support, information, and discuss the implications of a diagnosis for the individual and their family.
Frequently asked questions
What is the difference between HbC disease and HbC trait?
HbC disease occurs when someone inherits two altered copies of the HBB gene, one from each parent. HbC trait means a person has only one altered HBB gene and one normal gene, making them a carrier but generally not experiencing symptoms of the disease.
Will my children inherit HbC disease?
The inheritance pattern is autosomal recessive. If you have HbC disease, you will pass one altered HBB gene to all your children. If your partner also carries an altered HBB gene (e.g., HbC trait or another haemoglobinopathy), your children could inherit HbC disease or another related condition. Genetic counselling can provide specific risk information for your family.
Can HbC disease become more severe over time?
HbC disease is generally a stable and mild condition. While symptoms like mild anaemia or an enlarged spleen can persist, it typically does not become more severe with age. Regular medical check-ups help monitor for any changes or complications.
Are there any dietary restrictions for someone with HbC disease?
Generally, there are no specific dietary restrictions. A balanced and healthy diet is recommended for overall well-being. Your doctor may advise on folic acid supplementation to support red blood cell production, but this should always be discussed with a healthcare professional.
Is HbC disease linked to any other health problems?
While typically mild, some individuals with HbC disease may have a slightly increased risk of developing gallstones. An enlarged spleen is also common but rarely causes significant health issues. It is not generally linked to other major health problems.
References
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- Aljabry M, Sulimani S, Alotaibi G. Regional Prevalence of Hemoglobin C Across Saudi Arabia: An Epidemiological Survey. Journal of epidemiology and global health. 2024. PMID: 38372896
- Regragui I, Mamad H, El Mokhtari N. Hematological Profile of Hemoglobin C Disease: A Retrospective Study. Cureus. 2025. PMID: 40196068
- Okoh MP, Alli LA, Tolvanen MEE. Herbal Drug use in Sickle Cell Disease Management; Trends and Perspectives in Sub-Saharan Africa - A Systematic Review. Current drug discovery technologies. 2019. PMID: 30277160
- Bhatti PK, Ghay R, Singh Narang G. Estimation of HbA1c Levels in Transfusion-Dependent Thalassemia Patients in Comparison With Normal Healthy Individuals. Cureus. 2024. PMID: 39651019
- Xu K, Zhao J, Dramé BSI. Rod-Shaped Hemoglobin Crystals: Clues to the Diagnosis of Hemoglobin C Disease. Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion. 2024. PMID: 38708168
- Lemonne N, Billaud M, Waltz X. Rheology of red blood cells in patients with HbC disease. Clinical hemorheology and microcirculation. 2016. PMID: 25335812
- Garrell-Salat X, Garcia-Arumi C, Bertolani Y. Tractional Retinal Detachment Related to Hemoglobin C Trait Retinopathy: A Case Report. Turkish journal of ophthalmology. 2023. PMID: 37870045