| Group / country | Sex and onset range | Genotype | Defining phenotype / labs | Course / outcome |
|---|---|---|---|---|
| Case 1, Japan | Male; onset 2 years, diagnosis 5 years | Compound heterozygote: maternal allele lacked exon 2; paternal allele had 2-bp deletion in exon 3 (HMOX1) | Recurrent fever, generalized erythematous rash, joint pain, marked hepatomegaly, asplenia, flat nasal bridge, frontal bossing, eyelid edema; leukocytosis 51,600/µL, thrombocytosis 226 × 10^4/µL, hemoglobin 4.9 g/dL, LDH 17,470 IU/L, ferritin 780 ng/mL, triglycerides 638 mg/dL, total cholesterol 552 mg/dL, bilirubin 0.1–0.3 mg/dL, serum heme 490 µM, very high haptoglobin 800–1200 mg/dL; hematuria/proteinuria; kidney/liver iron deposition; vacuolated monocytes; endothelial/coagulation-fibrinolysis abnormalities (pqac-00000001, pqac-00000009, pqac-00000017) | Severe multisystem disease; specific final outcome not stated in gathered evidence; first autopsy case reported in literature review context (pqac-00000016, pqac-00000017) |
| Cases 2–6, India | Mixed sexes: female, male, male, female, male; onset 6 months to 15 years; diagnosis 20 months to 16 years | Homozygous p.R44X nonsense mutation in all 5 cases; founder effect suggested; parental genotypes unknown/not done for some, heterozygous R44X/wild type in some families (pqac-00000010, pqac-00000017) | Shared tetrad/profile: fever, asplenia, hemolytic anemia, hematuria/proteinuria, absent jaundice; prominent forehead common; growth delay variable; hypertension in most, cerebral bleeding in some; labs: CRP 4.8–30.8 mg/dL, WBC 18.5–43.2 ×10^3/mL, platelets 100–137 ×10^4/mL (one not shown), ferritin 2,000 to 15,530 ng/mL, LDH 4,000 to 21,400 IU/L, bilirubin 0.02–1.2 mg/dL, high haptoglobin despite hemolysis (pqac-00000010, pqac-00000017) | Variable latent period, then often rapid deterioration. Case 2 died 5 months after diagnosis after hypertension/intracranial hemorrhage and fungal sepsis; Cases 3 and 6 also reportedly died soon after symptom onset; outcomes for Cases 4–5 unknown in gathered evidence (pqac-00000017) |
| Case 7, Iran | Female; onset 17 months, diagnosis 3 years | Homozygous p.K204X in exon 3; both parents heterozygous carriers; consanguineous Iranian parents (pqac-00000003, pqac-00000011, pqac-00000017) | High fever, tachypnea, respiratory distress, massive pericardial effusion, hepatomegaly with liver iron deposition, normal-sized spleen, prolonged/recurrent fever, hemolytic anemia; leukocytosis 33.0 ×10^3/mL, platelets 100 ×10^4/mL, ferritin 27,425 ng/mL, LDH 15,350 IU/L, AST/ALT 580/813 IU/L, bilirubin 0.8 mg/dL, hyperlipidemia (pqac-00000010, pqac-00000011, pqac-00000017) | Corticosteroid ineffective; progressive deterioration over 4 admissions; died of recurrent fever, bleeding, heart failure, and ascites; diagnosis made post-mortem by whole-exome sequencing (pqac-00000003, pqac-00000017) |
| Case 8, Turkey | Male; onset 3 months, diagnosis 20 months | Homozygous p.G139V missense mutation; son of consanguineous Turkish parents (pqac-00000000, pqac-00000011) | Microcytic anemia resistant to iron, progressive hepatosplenomegaly, transfusion dependence; liver biopsy: severe hemophagocytosis, Kupffer cell siderosis, extramedullary hematopoiesis; slight marrow hemophagocytosis; inflammatory markers remained high (IL-1β, IL-6, TNF-α, ferritin, CRP); WBC 19.9 ×10^3/mL, platelets 47.8 ×10^4/mL, ferritin 4,855 ng/mL, LDH 15,713 IU/L, bilirubin 0.2–1.6 mg/dL; decreased HO-1 activity with abnormal peroxidase function and increased urinary peroxidation products (pqac-00000000, pqac-00000011) | Treated with HLH2004 immunochemotherapy with sustained remission of HLH-like signs, but inflammatory activity persisted; paradoxical inflammatory response to red cell transfusion reported; longer-term outcome unknown in gathered evidence (pqac-00000011) |
| Case 9, USA | Male; onset 4 years, diagnosis 10 years | Compound heterozygote: paternal frameshift c.264_269delCTGG (p.L89Sfs*24) and maternal splice donor c.636+2T>A (pqac-00000002, pqac-00000010) | Interstitial lung disease with recurrent inflammatory flares; fatigue, intermittent fevers, dark urine, hypoxemia, hepatomegaly, poorly perfused hypoplastic spleen/hyposplenia, growth slowing, hemolytic anemia with schistocytes and Howell-Jolly bodies, hematuria/proteinuria; WBC 53.8 ×10^3/mL, platelets 91.4 ×10^4/mL, ferritin 1,980 ng/mL, LDH 19,706 IU/L, bilirubin 0.2 mg/dL; liver biopsy with mild sinusoidal fibrosis, microvesicular steatosis, Kupffer-cell iron; lung biopsy with extensive fibrotic nonspecific interstitial pneumonia, pleural fibrosis, scattered/pulmonary interstitial and intra-alveolar cholesterol granulomas; PBMCs failed to induce HO-1 with cobalt protoporphyrin (pqac-00000000, pqac-00000002, pqac-00000010) | Genetic testing for periodic fever syndromes/familial HLH initially negative; treated with corticosteroid, anti-IL-1R, anti-IL-6, and cyclosporine with minimal benefit; died at age 10 from respiratory failure; diagnosis established post-mortem by whole-exome sequencing (pqac-00000000, pqac-00000002, pqac-00000010) |


*Table: This table compacts the currently gathered human evidence for HMOX1 deficiency into case groups, highlighting genotype, hallmark phenotype/laboratory patterns, and outcomes. It is useful for quickly comparing the recurrent diagnostic denominators and notable phenotype expansions across the 9 reported cases.*