Hereditary spherocytosis: symptoms, inheritance, diagnosis and treatment

Sheffield Children’s explains that in hereditary spherocytosis (HS) the red blood cells have an abnormal, spherical shape instead of the normal doughnut shape and have a shortened life span because the spleen, which removes old or damaged cells, destroys them early. This destruction is called haemolysis and can result in anaemia.

Patient.info adds that there is a defect in the outer layer of the red blood cell, making it sphere-shaped and more fragile than usual. There are many different types of defect but they all produce similar problems.

Whether someone develops anaemia depends on the severity of haemolysis and how well the bone marrow compensates. People with fully compensated haemolysis are not anaemic and usually have a milder course.

UCLH explains the mechanism: the surface membrane of the red cells is not as strong as it should be, so when they pass through the spleen bits of membrane break off and the cells change from doughnut-shaped discs to spheres. When they break down, bilirubin builds up in the blood, which can turn the whites of the eyes and skin yellow (jaundice) and over time can form gallstones.

The usual features, according to Patient.info, are anaemia, jaundice (yellowing of the skin and whites of the eyes) and a large spleen, and they can happen at any time of life. Anaemia can make people feel tired and short of breath with little exercise. Jaundice occurs because red cells are broken down too fast for the body to clear the pigment released. The spleen enlarges because it has to work harder.

Severity varies. Patient.info says about 2 to 3 in 10 people have mild disease, with few or no symptoms, while about 6 to 7 in 10 have moderate or severe disease, half of whom are first diagnosed in childhood with anaemia.

Gallstones are common because more pigment passes through the liver and gallbladder. Sheffield Children’s says these can cause problems from the late teens onwards, and Patient.info notes the gallbladder is often removed at the same time as the spleen if there are symptoms.

UCLH says symptoms differ in severity, can appear at any age and are not always present at birth. In a child, anaemia can mean feeling very tired, irritable or poorly, looking pale or not growing as well as expected, while older children and adults may tire when they exercise. People with severe symptoms often need regular transfusions. UCLH adds that jaundice is reversible and may vary in intensity over time.

Patient.info says the changes in the red blood cells can be seen through a microscope when a blood sample is sent to the laboratory, and that reticulocytes, young red cells, may also be increased because red cells are being broken down too quickly. Other blood tests may be needed to rule out other causes of red cell changes, such as liver disease, zinc toxicity and some infections. A doctor may also find an enlarged spleen on examining the tummy.

Most people with HS need no treatment other than folic acid, which supports the bone marrow’s increased production of red cells, according to Sheffield Children’s. Patient.info lists folate tablets, blood transfusions if there is severe anaemia, and spleen removal as treatment options, and notes that a normal diet will not meet the increased folate demand.

Removing the spleen (splenectomy) can control the disease because red cells survive much longer, but it increases the risk of life-threatening infection. Patient.info says people will need lifelong preventative antibiotics, vaccination against various infections, and should carry a card or wear a bracelet explaining they have had a splenectomy. Research suggests removing only part of the spleen may also work, but more evidence is needed.

Most children have mild disease, do not need splenectomy and have a normal life expectancy, according to Patient.info. Sheffield Children’s warns that, whatever the severity, a viral infection can cause a crisis, and that aplastic crisis is the more dangerous and needs immediate contact with the clinic if there is sudden tiredness with a pale appearance.

UCLH says people are seen in clinic at least once a year, and that folic acid helps the bone marrow produce new red blood cells. It recommends waiting until a child is 5 years old before spleen removal, and says some surgeons remove only part of the spleen so that fewer red cells are destroyed and the spleen still works a bit, although this has not been proven in a clinical trial.

UCLH advises going to your local A&E if you notice sudden tiredness, poor appetite or feeding, or worsening jaundice or paleness. Sheffield Children's NHS Foundation Trust says that, whatever the severity, a viral infection can cause a crisis in which haemoglobin falls to a dangerously low level, and that the aplastic crisis is the more dangerous: contact the clinic immediately in the event of sudden tiredness with a pale appearance. Most crises need a blood transfusion.

UCLH also says a large spleen is more at risk of bleeding if it is knocked. People with a large spleen should not play contact sports, and should seek urgent medical advice after an injury to the abdomen or if they have abdominal pain. Parvovirus B19 (slapped cheek syndrome) can stop red cell production for up to 10 days.

If your spleen has been removed you are at higher risk of infections. UCLH says that if you have an infection, fever or an animal bite you should get prompt medical advice, because you may need antibiotics.

Patient.info describes three routes: autosomal dominant, where one affected parent gives a 50:50 chance to each child and which accounts for about 7 in 10 cases; autosomal recessive, where two abnormal genes are needed and carriers do not have the disorder; and a new mutation, where there is no family history.

It suggests that a genetic counsellor can advise about the risk of passing on a particular type of HS. Sheffield Children’s also advises people who are pregnant or planning pregnancy to alert the midwife and doctor, because newborns of affected parents may need monitoring for jaundice.

UCLH says that three out of four people affected have a family history, and that if a parent has HS each of their children has a 1 in 2 chance of having it. One in four have no family history, which may be because a parent has a very mild undiagnosed condition or because it is a new genetic mutation. The family DNA can now be analysed to find which gene is responsible.

Sheffield Children's says mild jaundice is common at birth because the liver is immature, but HS increases the risk of severe jaundice in the first few days after birth, which can damage the brain if not detected and treated in time. If you are pregnant or planning pregnancy and HS runs in the family, tell the midwife and the doctor in charge of your antenatal care so that special arrangements can be made to monitor your newborn.

Patient.info says most children have mild disease, do not need splenectomy and have a normal life expectancy. UCLH recommends waiting until a child is 5 before splenectomy, and Sheffield Children's notes that gallstone problems can begin from the late teens onwards.