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Hereditary persistence of fetal haemoglobin
HPFH is generally considered a benign condition. It means that individuals maintain higher levels of foetal haemoglobin (HbF) in their red blood cells throughout their lives, which can sometimes reduce the severity of other inherited blood disorders.
Overview
Hereditary persistence of foetal haemoglobin (HPFH) is a group of benign genetic conditions characterised by the continued production of foetal haemoglobin (HbF) into adulthood [PMID:33678077]. Normally, after birth, the body switches from making HbF to adult haemoglobin (HbA). In individuals with HPFH, this switch is incomplete, or the production of HbF is prolonged. This condition is often discovered incidentally during routine blood tests or when investigating other blood disorders. HPFH itself typically does not cause health problems.
Symptoms & clinical features
Individuals with hereditary persistence of foetal haemoglobin (HPFH) generally do not experience any symptoms. The condition is usually asymptomatic, meaning it does not cause illness or noticeable health issues [PMID:33678077]. Many people with HPFH live their entire lives without knowing they have the condition unless it's identified through genetic testing or specific blood tests. However, the presence of higher HbF levels can be beneficial in certain circumstances, particularly for individuals who also have other haemoglobin disorders, as HbF can partially compensate for the faulty adult haemoglobin.
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Affected organs
Hereditary persistence of foetal haemoglobin primarily affects the blood, specifically red blood cells. The condition causes a change in the type of haemoglobin produced within these cells. It does not typically lead to direct damage or dysfunction of any organs. The impact is at a molecular level, affecting the oxygen-carrying capacity within the red blood cells, but usually without clinical consequences in isolation.
Risks & severity
HPFH is generally considered a benign condition, meaning it does not typically lead to serious health risks or complications on its own. The severity of HPFH varies depending on the underlying genetic change, with some forms resulting in higher HbF levels than others. However, even with elevated HbF, individuals are usually asymptomatic. The main significance of HPFH lies in its interaction with other inherited blood disorders, such as sickle cell anaemia or beta thalassaemia. In these cases, higher HbF levels can ameliorate the severity of the primary condition, acting as a natural protective mechanism [PMID:33678077]. For example, HbF can reduce sickling in sickle cell disease, leading to milder symptoms.
Genetic causes
Hereditary persistence of foetal haemoglobin can arise from different genetic changes. Key genes associated with HPFH include BCL11A and KLF1. The BCL11A gene provides instructions for making a protein that plays a crucial role in the switch from foetal to adult haemoglobin production [PMID:24606132]. Variants in BCL11A can disrupt this switch, leading to continued HbF production. Similarly, the KLF1 gene is also involved in regulating the production of haemoglobin. Pathogenic changes in KLF1 can also affect the balance of foetal versus adult haemoglobin, contributing to HPFH [PMID:22019912]. There are also other forms of HPFH that involve deletions in the beta-globin gene cluster, which directly affect the genes responsible for adult haemoglobin production.
- BCL11A BCL11 transcription factor A
- KLF1 KLF transcription factor 1
Inheritance pattern
Hereditary persistence of foetal haemoglobin can be inherited in either an autosomal dominant or an autosomal recessive pattern, depending on the specific genetic cause. In autosomal dominant inheritance, only one copy of the altered gene in each cell is sufficient to cause the condition. This means if a parent has the condition, there is a 50% chance their child will also inherit it. In autosomal recessive inheritance, two copies of the altered gene are needed for the condition to manifest. This means a child must inherit one altered copy from each parent to be affected. Parents who each carry one copy of an autosomal recessive HPFH variant are typically unaffected themselves, but have a 25% chance with each pregnancy of having a child with the condition.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
Diagnosis of hereditary persistence of foetal haemoglobin is typically made through specific blood tests that measure the percentage of foetal haemoglobin (HbF) in red blood cells. A blood test called haemoglobin electrophoresis or high-performance liquid chromatography (HPLC) can identify and quantify different types of haemoglobin. If elevated HbF levels are found, genetic testing may be offered to determine the specific genetic cause. Genetic testing for HPFH is covered by the NHS Genomic Medicine Service under various R-codes, often as part of a wider investigation for haemoglobinopathies. Referrals for genetic testing and counselling are usually made by a haematologist or a clinical geneticist.
Management & lifestyle
As hereditary persistence of foetal haemoglobin is generally a benign condition and typically does not cause symptoms, specific medical management is often not required. The primary 'management' aspect involves accurate diagnosis to distinguish it from other haemoglobin disorders and to understand its potential interaction with other genetic blood conditions. Individuals found to have HPFH, particularly if it's discovered in the context of other haemoglobinopathies, should have access to specialist haematology care within the NHS. Genetic counselling can be helpful for individuals and families to understand the inheritance pattern, the implications for family planning, and the potential impact of HPFH when co-inherited with other haemoglobin disorders. Regular monitoring is not usually needed for HPFH itself.
UK care pathway
In the UK, individuals suspected of having hereditary persistence of foetal haemoglobin or other haemoglobin disorders are typically referred to a haematologist. If a genetic cause is suspected or confirmed, referral to a clinical genetics service is an important step. These services provide expert diagnosis, genetic counselling, and support. Genetic testing for haemoglobinopathies, including HPFH, falls under the NHS Genomic Medicine Service and is generally initiated by specialist clinicians. Genetic counsellors play a vital role in explaining the condition, its inheritance, and implications for families.
Frequently asked questions
What does 'foetal haemoglobin' mean?
Foetal haemoglobin (HbF) is a type of haemoglobin produced during foetal development and shortly after birth. It has a higher affinity for oxygen, which helps the developing foetus get oxygen from the mother's blood. Normally, HbF production switches to adult haemoglobin (HbA) production during infancy.
Is hereditary persistence of foetal haemoglobin a serious condition?
Hereditary persistence of foetal haemoglobin (HPFH) is generally not considered a serious condition on its own. Most individuals with HPFH do not experience any health problems or symptoms related to it. It can even be beneficial if someone also has another blood disorder.
Can HPFH affect my children?
Yes, HPFH is a genetic condition, so it can be passed on to children. The inheritance pattern can be autosomal dominant or autosomal recessive, depending on the specific genetic change. Genetic counselling can provide more personalised information about the risk to your children.
Does having HPFH require special treatment or diet?
No, for most individuals, hereditary persistence of foetal haemoglobin does not require any special treatment, medication, or specific dietary changes. Since it typically causes no symptoms, the main approach is often just awareness of the diagnosis, especially if planning a family or if other blood conditions are present.
How is HPFH diagnosed?
HPFH is typically diagnosed through specialised blood tests such as haemoglobin electrophoresis or high-performance liquid chromatography (HPLC), which can measure the levels of different types of haemoglobin. If these tests show elevated foetal haemoglobin, genetic testing may be used to identify the specific genetic cause.
References
- Thein SL. Beta-thalassaemia. Bailliere's clinical haematology. 1998. PMID: 10872474
- Weatherall DJ, Clegg JB. Hereditary persistence of fetal haemoglobin. British journal of haematology. 1975. PMID: 1103943
- Poncz M, Henthorn P, Stoeckert C. Globin gene expression in hereditary persistence of fetal haemoglobin and (delta beta) (0)-thalassaemia. Oxford surveys on eukaryotic genes. 1988. PMID: 2472152
- Wood WG, Clegg JB, Weatherall DJ. Hereditary persistence of fetal haemoglobin (HPFH) and delta beta thalassaemia. British journal of haematology. 1979. PMID: 93487
- Serjeant GR, Serjeant BE, Mason KP. Newborn screening for abnormal haemoglobins in Jamaica: Practical issues in an island programme. Journal of medical screening. 2022. PMID: 35934992
- Murray N, Serjeant BE, Serjeant GR. Sickle cell-hereditary persistence of fetal haemoglobin and its differentiation from other sickle cell syndromes. British journal of haematology. 1988. PMID: 2454649
- Knox-Macaulay HH, Weatherall DJ, Clegg JB. Thalassaemia in the British. British medical journal. 1973. PMID: 4124395
- Serjeant GR, Serjeant BE, Mason K. Heterocellular hereditary persistence of fetal haemoglobin and homozygous sickle-cell disease. Lancet (London, England). 1977. PMID: 66587