Symptoms, Flares, and Organ Involvement
At a Glance
HO-1 deficiency can affect several organs and the blood and immune system. Patients may develop anemia, loss of spleen function, lung, kidney, or liver problems, and fast-moving inflammatory flares with persistent fever require urgent specialist care.
Because the Heme Oxygenase-1 (HO-1) enzyme is needed by almost every organ to manage iron and inflammation, its absence causes a multisystem disorder. This means it affects many parts of the body simultaneously [1]. However, because the condition is so rare, no two patients look exactly alike; some may have severe lung issues, while others primarily experience kidney or blood-related symptoms [2][3].
Chronic Organ Involvement
Over time, the inability to properly recycle iron and “calm” inflammation can lead to progressive damage in specific organs. Note that the following are findings reported in published case studies; not every patient will experience all of these:
- Lungs: Some patients develop interstitial lung disease (ILD), a condition where the tissues of the lungs become scarred or inflamed, making it hard to breathe [4]. In some cases, doctors have found cholesterol granulomas—small clumps of immune cells and crystals—inside the lung tissue [1].
- Kidneys: The kidneys can become inflamed, a condition known as nephritis [1]. In one adult patient, chronic inflammation eventually led to AA-type amyloidosis, where abnormal proteins build up in the kidneys and interfere with their ability to filter waste [2].
- Liver: It is commonly reported for the liver to become enlarged (hepatomegaly) [3]. This may be accompanied by hepatitis (liver inflammation) or elevated liver enzymes in the blood, often because iron is depositing directly into the liver tissue [1][3].
Hematological and Immune Issues
HO-1 deficiency profoundly changes how the blood and immune system function.
- Hemolytic Anemia: This is a condition where red blood cells are destroyed faster than the body can replace them [4]. As discussed in the orientation, this anemia is unique because it often occurs with unusually low bilirubin levels [3].
- Asplenia (Missing Spleen): Many patients are born without a functioning spleen or lose splenic function early on [1]. The spleen is a vital part of the immune system that filters bacteria from the blood. Imaging alone cannot confirm if a spleen works; a blood smear is often used. Without normal splenic function, patients are at a much higher risk for severe, life-threatening infections [1].
- Abnormal Blood Counts: During periods of stress, the body may produce too many white blood cells (leukocytosis) or too many platelets (thrombocytosis) [1][3].
Acute Hyperinflammatory Flares
One of the most challenging aspects of HO-1 deficiency is the tendency for “flares”—sudden, intense episodes of systemic inflammation usually triggered by a common viral or bacterial infection [1][4].
These flares often look like a condition called Macrophage Activation Syndrome (MAS) or Hemophagocytic Lymphohistiocytosis (HLH) [1]. During these episodes, the immune system becomes overactive, contributing to severe immune dysregulation. Symptoms of a flare can include:
- High, persistent fevers [3].
- Rapidly worsening anemia or low blood counts [4].
- Fluid buildup around the heart (pericardial effusion) or in the abdomen (ascites) [3].
- Increased risk of bleeding, such as pulmonary hemorrhage (bleeding in the lungs) [4].
Because these flares can progress very quickly, they require close medical supervision and often involve specialized medications to manage the immune response [4][3].
Common questions in this guide
What parts of the body can HO-1 deficiency affect?
Why can a fever be an emergency with HO-1 deficiency?
What does asplenia mean for someone with HO-1 deficiency?
Can HO-1 deficiency cause anemia with low bilirubin?
Which organ problems should be monitored in HO-1 deficiency?
What signs may point to a hyperinflammatory flare?
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Lung involvement
How would you check whether my lungs are affected?
Kidney involvement
Could the kidneys become inflamed in my case?
Flare symptoms
What symptoms of a flare should I watch for?
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References
References (4)
- 1
Heme oxygenase-1 deficiency presenting with interstitial lung disease and hemophagocytic flares.
Chau AS, Cole BL, Debley JS, et al.
Pediatric rheumatology online journal 2020; (18(1)):80 doi:10.1186/s12969-020-00474-1.
PMID: 33066778 - 2
Heme oxygenase-1 deficiency as an extremely rare cause of AA-type renal amyloidosis: Expanding the clinical features and review of the literature.
Dirim AB, Kalayci T, Safak S, et al.
Clinical rheumatology 2023; (42(2)):597-606 doi:10.1007/s10067-022-06465-9.
PMID: 36502441 - 3
Post-mortem Diagnosis of Heme Oxygenase-1 Deficiency by Whole Exome Sequencing in an Iranian Child.
Tahghighi F, Parvaneh N, Ziaee V
International journal of molecular and cellular medicine 2019; (8(4)):300-307 doi:10.22088/IJMCM.BUMS.8.4.300.
PMID: 32587840 - 4
Clinical and molecular analysis of a novel variant in heme oxygenase-1 deficiency: Unraveling its role in inflammation, heme metabolism, and pulmonary phenotype.
Berendes LS, Westhoff PS, Wittkowski H, et al.
Molecular genetics and metabolism reports 2024; (38()):101038 doi:10.1016/j.ymgmr.2023.101038.
PMID: 38178812
This page is for informational purposes only and does not constitute medical advice about HO-1 deficiency. A qualified medical team should urgently assess high fever, breathing problems, bleeding, or signs of severe infection.