HEMPAS – Hereditary Erythroblast Multinuclearity with Positive Acid Serum Test is a rare inherited blood disease. Its full old name is hereditary erythroblastic multinuclearity with positive acidified serum test. Today, doctors usually call it congenital dyserythropoietic anemia type II, or CDA II. In this disease, the bone marrow makes red blood cells in a wrong way, so many cells do not grow into strong, healthy red blood cells. This causes long-term anemia and can also cause jaundice, an enlarged spleen, gallstones, and extra iron in the body. 1 2 3
HEMPAS is the older name for congenital dyserythropoietic anemia type II (CDA II). It is a rare inherited red blood cell disorder in which the bone marrow makes red blood cells in an abnormal way, so many cells die before they fully mature. This causes chronic anemia, jaundice, an enlarged spleen, gallstones, and iron overload, even in some people who do not receive many transfusions. CDA II is usually linked to SEC23B gene changes and is commonly inherited in an autosomal recessive pattern. [1]
HEMPAS happens because a child is born with harmful changes in a gene, most often the SEC23B gene. This gene helps move proteins inside cells. When it does not work well, young red blood cells develop abnormally. Many of them die early inside the bone marrow, and some of the red blood cells that do enter the blood are also broken down too fast. 2 4 5
Other names
Other names for HEMPAS include CDA II, congenital dyserythropoietic anemia type II, CDAN2, HEMPAS anemia, SEC23B-related CDA II, and the longer form hereditary erythroblastic multinuclearity with positive acidified-serum test. These names all point to the same disorder or the same disease group. The old name came from two classic findings: many red blood cell precursors had more than one nucleus, and the red cells reacted abnormally in an old acidified serum test. 3 6 7
Types
Type 1: CDA I. This is a different form of congenital dyserythropoietic anemia. It is not HEMPAS, but it belongs to the same disease family. It has different genes and different bone marrow changes. 2 8
Type 2: CDA II or HEMPAS. This is the form asked about here. It is the most common CDA type. It is usually linked to SEC23B changes and is known for multinucleated erythroblasts, anemia, jaundice, splenomegaly, and iron overload over time. 1 4 9
Type 3: CDA III. This is another rare type. It is different from HEMPAS and has its own genes and blood cell findings. Doctors separate it from CDA II by bone marrow appearance and genetic testing. 2 9
Type 4 and rarer forms. Some patients have other very rare CDA types, such as type IV or CDA-like disorders. These may look similar at first, but genetic testing helps tell them apart from HEMPAS. 2 9
Causes
There is really one main direct cause of HEMPAS: harmful changes in both copies of the SEC23B gene. To help you fully study the disease, the next 20 short paragraphs give the main cause plus closely related cause-mechanism points and family factors that explain why the disease happens and why it becomes worse in some people. 2 4
1. SEC23B gene changes. This is the main cause in classic HEMPAS. A child usually gets one changed copy from the mother and one from the father. 2 4
2. Autosomal recessive inheritance. The disease appears when both gene copies are affected. Parents are often healthy carriers. 2 1
3. Faulty protein transport inside cells. SEC23B helps move proteins from one part of the cell to another. When this pathway fails, red cell development is disturbed. 4 5
4. Abnormal erythroblast maturation. Young red blood cells in the bone marrow do not mature in the usual step-by-step way. 2 9
5. Ineffective erythropoiesis. The marrow tries to make red blood cells, but many cells die before they become useful mature cells. 1 9
6. Multinuclearity of erythroblasts. Some developing red cells keep two or more nuclei. This is one reason the old name includes “multinuclearity.” 6 10
7. Membrane glycosylation defect. The surface proteins of red cells do not get normal sugar chains. This changes how the cells behave. 7 5
8. Abnormal band 3 glycoprotein. Band 3 on the red cell membrane is often under-glycosylated. This is a classic lab clue in HEMPAS. 7 5
9. Early destruction inside the marrow. Many abnormal cells are removed before entering the bloodstream. This adds to anemia. 1 9
10. Extra destruction in the spleen. The spleen removes weak or odd-shaped red cells faster than normal. 1 5
11. Positive acidified serum lysis reaction. The old HEMPAS test showed that red cells broke more easily in acidified serum because of membrane changes. 6 11
12. Chronic hemolysis. Some red blood cells that reach the blood are fragile and break down too soon. 1 3
13. Family carrier status. If both parents carry a harmful SEC23B variant, the chance for an affected child rises. 2 1
14. Related rare genetic mimics. A few rare disorders can look like HEMPAS, including some glycosylation disorders, but classic HEMPAS is still mainly SEC23B-related. 7 12
15. Different mutation types. Missense, splice, frameshift, and other SEC23B variants can all cause CDA II. 13 4
16. Variant severity differences. Some gene changes cause milder anemia, while others cause more severe disease. 13 14
17. Iron loading from the disease itself. Even without many transfusions, the body may absorb too much iron because red cell production is ineffective. 1 6
18. Transfusions can add more iron. In severe cases, repeated blood transfusions increase iron overload. This is not the root cause of HEMPAS, but it can worsen body damage. 1 3
19. Gallstone formation from hemolysis. Ongoing red cell breakdown raises bilirubin and can lead to pigment gallstones. 1 10
20. Long-term organ burden. Chronic anemia, hemolysis, and iron overload together can affect the spleen, liver, and general health over time. 1 3
Symptoms
1. Tiredness. Low red blood cells mean less oxygen reaches the body, so the person may feel weak and tired. 2 3
2. Pale skin. Pallor is common in anemia because there are fewer healthy red blood cells carrying hemoglobin. 15 10
3. Shortness of breath on effort. Walking fast or climbing stairs may feel hard when anemia is present. 3 15
4. Fast heartbeat. The heart may beat faster to carry more oxygen around the body. 15 2
5. Jaundice. The skin or eyes may look yellow because red blood cells break down and bilirubin rises. 1 3
6. Enlarged spleen. The spleen may grow bigger because it is trapping and removing weak red blood cells. 1 10
7. Enlarged liver. Some patients also have a larger liver, especially when hemolysis or iron loading is present. 4 2
8. Gallstones. Repeated red cell breakdown can form pigment stones in the gallbladder. 1 3
9. Belly discomfort. Large spleen, large liver, or gallstones can cause upper abdominal pain or fullness. 1 15
10. Dark urine at times. Increased bilirubin or hemolysis may make urine darker in some patients. 15 3
11. Poor exercise tolerance. Children or adults may get tired more quickly than others during play or work. 2 15
12. Growth problems in severe cases. Severe, long-lasting anemia can affect normal growth in some children. 3 9
13. Iron overload symptoms later. Extra iron can slowly damage organs and may later cause weakness, liver problems, or hormone problems. 1 6
14. Need for transfusions in some patients. A smaller group has more severe anemia and may need blood transfusions. 6 1
15. Symptoms can vary a lot. Some people have mild disease and are found late, while others are diagnosed in childhood because symptoms are stronger. 10 9
Diagnostic tests
1. Medical history. The doctor asks about long-term anemia, jaundice, gallstones, transfusions, and family history. This helps raise suspicion for an inherited anemia. 9 15
2. Physical exam. The doctor looks for pallor, yellow eyes, large spleen, large liver, and signs of chronic anemia. 1 15
3. Manual spleen and liver palpation. This is a hands-on bedside check. The doctor gently feels the abdomen to see if the spleen or liver is enlarged. 1 15
4. Complete blood count. CBC measures hemoglobin and red cell numbers. It shows anemia and helps judge severity. 9 15
5. Reticulocyte count. This measures young red cells in blood. In CDA II, the count may be lower than expected for the amount of anemia because red cell production is ineffective. 1 9
6. Peripheral blood smear. A lab worker and doctor look at blood under a microscope. This can show abnormal red cell shape and support the diagnosis. 9 10
7. Bilirubin test. Bilirubin often rises when red blood cells break down more quickly than normal. 1 15
8. Lactate dehydrogenase and haptoglobin. These are hemolysis markers. They help show ongoing red cell destruction. 15 9
9. Iron studies. Ferritin, transferrin saturation, and related tests help check iron overload, which is common with age. 1 6
10. Bone marrow aspirate. This is one of the key tests. It shows erythroid hyperplasia and many binuclear or multinuclear erythroblasts. 6 10
11. Bone marrow pathology review. A pathologist studies the marrow cells carefully to separate CDA II from other marrow diseases and from other CDA types. 9 10
12. Acidified serum lysis test. This old classic test is the reason for the name HEMPAS. It is less used today, but historically it showed abnormal red cell lysis in acidified serum. 6 11
13. SDS-PAGE of red cell membrane proteins. This special lab test can show the typical abnormal band 3 glycosylation pattern seen in CDA II. 5 16
14. Red cell membrane glycoprotein analysis. This is another way to study the membrane sugar pattern and supports the diagnosis in specialized centers. 7 5
15. Genetic testing for SEC23B. This is now a major confirmatory test. Finding disease-causing variants in both copies of SEC23B strongly supports classic CDA II. 4 13
16. Family testing. Testing parents or siblings can show carrier status or identify others with the disease. This helps with diagnosis and family planning. 2 13
17. Ultrasound of abdomen. This imaging test looks for enlarged spleen, enlarged liver, and gallstones. 1 15
18. MRI for iron overload. MRI, especially of the liver and sometimes the heart, helps measure excess iron in the body without surgery. 1 9
19. Tests to rule out similar diseases. Doctors may order Coombs testing, hemoglobin studies, enzyme tests, or other tests to exclude more common causes of anemia and hemolysis. 9 15
20. About electrodiagnostic tests. Standard electrodiagnostic tests are not routine tests for HEMPAS. The diagnosis mainly depends on history, exam, blood tests, marrow study, specialized membrane studies, genetics, and imaging. This is important because HEMPAS is a blood production disorder, not a nerve or muscle disease. 9 16
It is a rare inherited disorder of red blood cell formation, most often caused by harmful changes in SEC23B. The main problems are chronic anemia, jaundice, enlarged spleen, gallstones, and iron overload. The most useful modern diagnostic tools are CBC, reticulocyte count, blood smear, hemolysis tests, iron tests, bone marrow study, abdominal imaging, and especially genetic testing. 1 2 4
Non-Pharmacological Treatments
1) Regular hematology follow-up. This means planned checkups with blood counts, bilirubin, reticulocytes, ferritin, liver tests, and sometimes MRI for iron. The purpose is to catch anemia worsening, iron overload, liver injury, and spleen enlargement early. The mechanism is simple: repeated monitoring lets doctors act before permanent organ damage happens. [3]
2) Red blood cell transfusion when needed. This is used for severe anemia, major symptoms, growth problems, pregnancy stress, infection stress, surgery, or very low hemoglobin. The purpose is to improve oxygen delivery. The mechanism is that healthy donor red cells temporarily replace the patient’s poorly effective red cell production. [4]
3) Iron overload surveillance. Many people with CDA II absorb too much iron because of ineffective erythropoiesis, even without many transfusions. The purpose is to protect the liver, heart, and endocrine organs. The mechanism is early detection through ferritin and liver iron assessment so iron can be reduced before organ injury. [5]
4) MRI-based liver iron assessment. MRI can estimate iron burden more accurately than ferritin alone in some patients. The purpose is to guide treatment intensity. The mechanism is noninvasive measurement of tissue iron concentration, which helps doctors decide whether chelation or phlebotomy is needed. [6]
5) Phlebotomy in selected patients. Some mildly affected people who are not very anemic but have excess iron may benefit from carefully supervised blood removal. The purpose is to lower body iron. The mechanism is that iron leaves the body with removed blood, forcing the body to use stored iron. This is only for selected patients because many are already anemic. [7]
6) Splenectomy in selected severe cases. This surgery removes the spleen. The purpose is to reduce red cell destruction and improve hemoglobin in patients with marked splenomegaly or transfusion need. The mechanism is reduced pooling and destruction of fragile red cells. It is not routine for everyone. [8]
7) Cholecystectomy for gallstones. CDA II often causes pigment gallstones because chronic hemolysis raises bilirubin. The purpose is to treat pain, infection, or blocked bile flow. The mechanism is removal of the gallbladder, which removes the source of repeated gallstone attacks. [9]
8) Vaccination planning before or after splenectomy. People without a spleen need special vaccine protection. The purpose is to lower the risk of severe infection from encapsulated bacteria. The mechanism is immune priming with vaccines such as Hib, pneumococcal, and meningococcal vaccines, ideally before elective splenectomy when possible. [10]
9) Infection prevention education. Patients and families should learn to seek urgent care for fever, especially after splenectomy. The purpose is early treatment of potentially dangerous infection. The mechanism is rapid recognition and fast antibiotic evaluation before infection becomes overwhelming. [11]
10) Genetic counseling. Because CDA II is inherited, family counseling is important. The purpose is to explain recurrence risk, testing of relatives, and reproductive planning. The mechanism is identification of the responsible gene and inheritance pattern so families can make informed decisions. [12]
11) Confirmatory molecular testing. Genetic confirmation, often with SEC23B analysis, helps separate CDA II from thalassemia and other anemias. The purpose is accurate diagnosis. The mechanism is direct detection of the disease-causing variant, which improves counseling and management planning. [13]
12) Bone marrow review by an expert. Multinuclear erythroblasts are a classic clue. The purpose is correct diagnosis in difficult cases. The mechanism is microscopic review of marrow morphology, which can show the dyserythropoiesis typical of CDA II. [14]
13) Pregnancy planning with specialists. Some patients may worsen during pregnancy or need transfusion support. The purpose is maternal and fetal safety. The mechanism is coordinated care with hematology and obstetrics, with close monitoring for anemia, iron, and fetal growth. [15]
14) Growth and development monitoring in children. Chronic anemia can affect energy, school function, and growth. The purpose is early support. The mechanism is regular review of height, weight, puberty, and fatigue so intervention can be started early. [16]
15) Liver health follow-up. Iron overload can injure the liver over time. The purpose is prevention of fibrosis, cirrhosis, and endocrine complications. The mechanism is serial liver tests, iron monitoring, imaging, and treatment of excess iron. [17]
16) Endocrine screening. Chronic iron overload can affect glucose control, puberty, thyroid, and other hormone systems. The purpose is early detection of organ injury. The mechanism is targeted lab tests and specialist review when iron burden becomes significant. [18]
17) Nutrition support. Good nutrition does not cure CDA II, but it supports marrow function and general health. The purpose is to reduce additional nutrient-related anemia. The mechanism is ensuring adequate folate, B12, protein, and micronutrient intake while avoiding unnecessary iron loading. [19]
18) Fatigue management and energy pacing. Many patients feel tired because of chronic anemia. The purpose is better daily function. The mechanism is balancing rest and activity so oxygen demand does not exceed what the blood can deliver. [20]
19) Avoiding unnecessary iron supplements. Routine iron should not be used unless true iron deficiency is proven. The purpose is to prevent worsening iron overload. The mechanism is reducing extra iron entry into a body that may already accumulate too much iron. [21]
20) Hematopoietic stem cell transplant in extreme cases. This is the only potentially curative option, but it is reserved for very severe disease because it carries major risk. The purpose is cure. The mechanism is replacement of the abnormal marrow with healthy donor stem cells. [22]
Drug Treatment Reality for HEMPAS
For HEMPAS/CDA II, the strongest medicine evidence is for supportive drugs, especially iron chelators in iron overload. There is no standard FDA-approved disease-specific medicine that fixes the SEC23B defect itself. Also, erythropoietin has not shown clear benefit in CDA II, and folate/B12 are often used but not clearly proven to change the core disease. [23]
1) Deferasirox. This oral iron chelator is one of the most important medicines when CDA II causes chronic iron overload, especially after transfusions or with high liver iron. Drug class: iron chelator. Typical starting regimens depend on the product and iron burden; FDA labeling warns about renal failure, hepatic failure, and gastrointestinal bleeding risk. Purpose: lower body iron. Mechanism: it binds iron so it can be excreted. Common side effects include stomach upset, rash, and kidney or liver toxicity, so monitoring is essential. [24]
2) Deferoxamine. This older iron chelator is given by infusion or injection and is useful when iron overload is severe or oral therapy is unsuitable. Drug class: iron chelator. FDA labeling includes subcutaneous and intravenous use, with dosing often individualized by weight and iron burden. Purpose: remove excess iron. Mechanism: it chelates ferric iron and increases excretion. Side effects can include infusion reactions, visual or hearing toxicity, and infection concerns in some settings. [25]
3) Deferiprone. This oral iron chelator is another option, especially when other chelation is inadequate or not tolerated. Drug class: iron chelator. FDA labeling emphasizes use in transfusional iron overload due to thalassemia syndromes when current chelation is inadequate, so its use in CDA II is generally extrapolated supportive practice, not disease-specific approval. Mechanism: binds iron for urinary excretion. Side effects include nausea, joint pain, liver enzyme rise, and important risk of neutropenia or agranulocytosis. [26]
4) Folic acid. This is commonly given in chronic hemolytic states because red cell production uses folate. Drug class: vitamin supplement. Dose varies by clinician and patient status. Purpose: support erythropoiesis and prevent superimposed folate deficiency. Mechanism: folate supports DNA synthesis in rapidly dividing marrow cells. In CDA II, it is often used, but Orphanet notes that clear proof of efficacy is lacking. [27]
5) Vitamin B12 when deficiency is present or suspected. This is not a core cure for CDA II, but it may help if there is coexisting deficiency or if folate is being used and B12 status is uncertain. Purpose: support normal DNA synthesis and avoid masking B12 deficiency. Mechanism: it supports marrow cell division and neurologic health. [28]
6) Peri-splenectomy antibiotics and vaccines. These are not disease-curing drugs, but they become very important if the spleen is removed. Purpose: reduce infection risk. Mechanism: antibiotic prophylaxis or rapid empiric treatment helps cover dangerous bacteria while vaccines reduce future severe infection risk. The exact antibiotic choice depends on age and local guidelines. [29]
7) Pain medicines for gallstone attacks or postoperative care. These treat symptoms, not the blood disorder itself. Purpose: control biliary pain and improve recovery. Mechanism: pain reduction lowers stress and supports hydration and nutrition while the underlying gallbladder issue is addressed surgically if needed. [30]
8) Transfusion support medicines such as antihistamines or antipyretics when clinically needed. These are supportive only. Purpose: reduce transfusion reactions in selected patients. Mechanism: symptom prevention around transfusion. Their use depends on prior reaction history and hospital protocol. [31]
9) Endocrine replacement drugs if iron overload damages organs. For example, some patients later need diabetes or thyroid treatment. Purpose: treat complications, not the root anemia. Mechanism: organ-specific hormone or metabolic replacement after iron injury. [32]
10) “Immunity booster” or “regenerative” drugs. At present, there is no established FDA-approved immunity-booster or regenerative drug that specifically treats HEMPAS/CDA II. The only truly curative biological approach described is allogeneic stem cell transplant in carefully selected severe cases, and that is a transplant procedure, not a routine medicine. [33]
Dietary Molecular Supplements
In CDA II, supplements are supportive only. The best-supported choices are those used to prevent extra deficiency, not to cure the gene disorder. Folate and B12 are the most commonly discussed; iron should not be taken unless deficiency is proven. [34]
Useful supportive supplements may include: folic acid, vitamin B12, vitamin D if low, calcium if dietary intake is poor, protein support in undernutrition, multivitamin without iron when diet is limited, omega-3 for general nutrition, zinc only if deficiency exists, vitamin C only with medical advice because it can affect iron handling, and oral rehydration/electrolyte support during illness. These help overall health, bone health, or deficiency correction, but none is proven to reverse CDA II marrow pathology. [35]
Surgeries
1) Splenectomy is done when splenomegaly is massive, anemia is severe, or transfusion need is high.
2) Cholecystectomy is done for symptomatic gallstones.
3) Central venous access procedures may be needed in heavily transfused patients.
4) Liver biopsy is rarely considered only in selected diagnostic situations, though MRI is preferred for iron.
5) Hematopoietic stem cell transplant procedure is used for very severe disease because it can be curative. [36]
Prevention Tips
Prevent problems by keeping regular follow-up, checking ferritin and liver iron, avoiding self-prescribed iron, treating severe anemia early, getting vaccines if splenectomy is planned, acting fast for fever, screening for gallstones, maintaining good nutrition, using genetic counseling before pregnancy, and following transplant-center advice if disease is very severe. These steps do not prevent the inherited mutation, but they can prevent many complications. [37]
When to See a Doctor
See a doctor urgently for very pale skin, worsening weakness, shortness of breath, chest pain, fever, yellow eyes getting worse, severe belly pain, dark urine, rapid spleen enlargement, transfusion reactions, or signs of iron overload such as liver problems or diabetes symptoms. People who have had splenectomy should treat fever as an emergency. [38]
What to Eat and What to Avoid
Eat folate-rich foods, B12-containing foods if not vegetarian, enough protein, fruits, vegetables, whole grains, good hydration, calcium/vitamin D foods, and balanced meals during illness recovery. Avoid or limit unnecessary iron supplements, alcohol excess, raw or unsafe foods after splenectomy or during severe illness, very restrictive diets, and self-medication without hematology advice. Diet supports health, but it does not cure the genetic disorder. [39]
FAQs
Is HEMPAS the same as CDA II? Yes. [40]
Is it inherited? Yes, usually autosomal recessive. [41]
What causes the anemia? Ineffective red cell production in the marrow. [42]
Can iron overload happen without many transfusions? Yes. [43]
Is folic acid proven to cure it? No, it is supportive only. [44]
Does erythropoietin work well? Not clearly in CDA II. [45]
Can splenectomy help? In selected patients, yes. [46]
Are gallstones common? Yes. [47]
Is there a cure? Stem cell transplant can be curative in severe selected cases. [48]
Do all patients need transfusions? No. Severity varies a lot. [49]
Can adults still have complications? Yes, especially iron overload, liver disease, and gallstones. [50]
Should patients take iron tablets? Not unless iron deficiency is proven. [51]
Why are vaccines important after splenectomy? Because infection risk rises. [52]
Can it be mistaken for thalassemia? Yes, sometimes. [53]
Is life expectancy always short? Not necessarily; many patients live long lives, but complications need monitoring. [54]
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: April 01, 2025.
