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Heme oxygenase 1 deficiency(HMOX1D)

MedGen UID:
333882
Concept ID:
C1841651
Disease or Syndrome
Synonym: HMOX1D
SNOMED CT: HO-1 (heme oxygenase-1) deficiency (1230003009); Heme oxygenase-1 deficiency (1230003009)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): HMOX1 (22q12.3)
 
Monarch Initiative: MONDO:0013536
OMIM®: 614034
Orphanet: ORPHA562509

Definition

Heme oxygenase-1 deficiency (HMOX1D) is a rare autosomal recessive disorder with a complex clinical presentation including direct antibody negative hemolytic anemia, low bilirubin, and hyperinflammation (summary by Chau et al., 2020). Other features may include asplenia and nephritis (Radhakrishnan et al., 2011). [from OMIM]

Clinical features

From HPO
Hematuria
MedGen UID:
5488
Concept ID:
C0018965
Disease or Syndrome
The presence of blood in the urine. Hematuria may be gross hematuria (visible to the naked eye) or microscopic hematuria (detected by dipstick or microscopic examination of the urine).
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Diffuse alveolar hemorrhage
MedGen UID:
1381751
Concept ID:
C4476767
Pathologic Function
A type of of pulmonary hemorrhage that originates from the pulmonary microcirculation, including the alveolar capillaries, arterioles, and venules. It presents with hemoptysis, anemia, diffuse lung infiltration, and acute respiratory failure. The diagnosis is confirmed by the observation of the accumulation of red blood cells, fibrin, or hemosiderin-laden macrophage in the alveolar space on pathologic biopsy. Hemosiderin, a product of hemoglobin degradation, appears at least 48-72 hours after bleeding and is helpful in distinguishing diffuse alveolar hemorrhage from surgical trauma. Mild interstitial thickening, organizing pneumonia, or diffuse alveolar damage can also be seen.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Hemolytic anemia
MedGen UID:
1916
Concept ID:
C0002878
Disease or Syndrome
A type of anemia caused by premature destruction of red blood cells (hemolysis).
Epistaxis
MedGen UID:
4996
Concept ID:
C0014591
Pathologic Function
Epistaxis, or nosebleed, refers to a hemorrhage localized in the nose.
Coombs-positive hemolytic anemia
MedGen UID:
105458
Concept ID:
C0520736
Disease or Syndrome
A type of hemolytic anemia in which the Coombs test is positive.
Thrombocytosis
MedGen UID:
163397
Concept ID:
C0836924
Disease or Syndrome
Increased numbers of platelets in the peripheral blood.
Nephritis
MedGen UID:
14328
Concept ID:
C0027697
Disease or Syndrome
The presence of inflammation affecting the kidney.
Sepsis
MedGen UID:
48626
Concept ID:
C0036690
Disease or Syndrome
Systemic inflammatory response to infection.
Cervical lymphadenopathy
MedGen UID:
66724
Concept ID:
C0235592
Disease or Syndrome
Enlarged lymph nodes in the neck.
Lymphadenopathy
MedGen UID:
96929
Concept ID:
C0497156
Disease or Syndrome
Enlargement (swelling) of a lymph node.
Increased circulating interleukin 6 concentration
MedGen UID:
901461
Concept ID:
C4280771
Finding
The concentration of interleukin-6 in the blood circulation is above the upper limit of normal.
Asplenia
MedGen UID:
1830315
Concept ID:
C5779621
Anatomical Abnormality
Absence (aplasia) of the spleen.
Elevated circulating aspartate aminotransferase concentration
MedGen UID:
57497
Concept ID:
C0151904
Finding
The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal.
Elevated circulating alanine aminotransferase concentration
MedGen UID:
57740
Concept ID:
C0151905
Finding
An abnormally high concentration in the circulation of alanine aminotransferase (ALT).
Increased circulating ferritin concentration
MedGen UID:
69130
Concept ID:
C0241013
Finding
Increased concentration of ferritin in the blood circulation.
Elevated circulating C-reactive protein concentration
MedGen UID:
892906
Concept ID:
C4023452
Finding
An abnormal elevation of the C-reactive protein level in the blood circulation.
Increased circulating lactate dehydrogenase concentration
MedGen UID:
1377250
Concept ID:
C4477095
Finding
An elevated level of the enzyme lactate dehydrogenase in the blood circulation.
Chemosis
MedGen UID:
124393
Concept ID:
C0271298
Pathologic Function
Edema (swelling) of the bulbar conjunctiva.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHeme oxygenase 1 deficiency

Recent clinical studies

Etiology

Yazdanbakhsh K
Transfus Clin Biol 2015 Aug;22(3):178-81. Epub 2015 Jun 6 doi: 10.1016/j.tracli.2015.05.005. PMID: 26056038Free PMC Article
Joe Y, Zheng M, Kim HJ, Uddin MJ, Kim SK, Chen Y, Park J, Cho GJ, Ryter SW, Chung HT
Am J Physiol Gastrointest Liver Physiol 2015 Jul 1;309(1):G21-9. Epub 2015 May 7 doi: 10.1152/ajpgi.00307.2014. PMID: 25951827
Gill AJ, Kovacsics CE, Cross SA, Vance PJ, Kolson LL, Jordan-Sciutto KL, Gelman BB, Kolson DL
J Clin Invest 2014 Oct;124(10):4459-72. Epub 2014 Sep 9 doi: 10.1172/JCI72279. PMID: 25202977Free PMC Article
Lee SE, Yang H, Jeong SI, Jin YH, Park CS, Park YS
PLoS One 2012;7(7):e41676. Epub 2012 Jul 25 doi: 10.1371/journal.pone.0041676. PMID: 22848562Free PMC Article
Fagone P, Mangano K, Coco M, Perciavalle V, Garotta G, Romao CC, Nicoletti F
Clin Exp Immunol 2012 Feb;167(2):179-87. doi: 10.1111/j.1365-2249.2011.04491.x. PMID: 22235993Free PMC Article

Diagnosis

Dirim AB, Kalayci T, Safak S, Garayeva N, Gultekin B, Hurdogan O, Solakoglu S, Yazici H, Cefle K, Ozturk S, Yildiz A
Clin Rheumatol 2023 Feb;42(2):597-606. Epub 2022 Dec 11 doi: 10.1007/s10067-022-06465-9. PMID: 36502441
Chau AS, Cole BL, Debley JS, Nanda K, Rosen ABI, Bamshad MJ, Nickerson DA, Torgerson TR, Allenspach EJ
Pediatr Rheumatol Online J 2020 Oct 16;18(1):80. doi: 10.1186/s12969-020-00474-1. PMID: 33066778Free PMC Article
Balla J, Vercellotti GM, Jeney V, Yachie A, Varga Z, Eaton JW, Balla G
Mol Nutr Food Res 2005 Nov;49(11):1030-43. doi: 10.1002/mnfr.200500076. PMID: 16208635
Kawashima A, Oda Y, Yachie A, Koizumi S, Nakanishi I
Hum Pathol 2002 Jan;33(1):125-30. doi: 10.1053/hupa.2002.30217. PMID: 11823983
Yachie A, Niida Y, Wada T, Igarashi N, Kaneda H, Toma T, Ohta K, Kasahara Y, Koizumi S
J Clin Invest 1999 Jan;103(1):129-35. doi: 10.1172/JCI4165. PMID: 9884342Free PMC Article

Therapy

Yazdanbakhsh K
Transfus Clin Biol 2015 Aug;22(3):178-81. Epub 2015 Jun 6 doi: 10.1016/j.tracli.2015.05.005. PMID: 26056038Free PMC Article
Schallner N, Pandit R, LeBlanc R 3rd, Thomas AJ, Ogilvy CS, Zuckerbraun BS, Gallo D, Otterbein LE, Hanafy KA
J Clin Invest 2015 Jul 1;125(7):2609-25. Epub 2015 May 26 doi: 10.1172/JCI78443. PMID: 26011640Free PMC Article
Fagone P, Mangano K, Coco M, Perciavalle V, Garotta G, Romao CC, Nicoletti F
Clin Exp Immunol 2012 Feb;167(2):179-87. doi: 10.1111/j.1365-2249.2011.04491.x. PMID: 22235993Free PMC Article
Blancou P, Tardif V, Simon T, Rémy S, Carreño L, Kalergis A, Anegon I
Methods Mol Biol 2011;677:247-68. doi: 10.1007/978-1-60761-869-0_18. PMID: 20941616
Loboda A, Jazwa A, Grochot-Przeczek A, Rutkowski AJ, Cisowski J, Agarwal A, Jozkowicz A, Dulak J
Antioxid Redox Signal 2008 Oct;10(10):1767-812. doi: 10.1089/ars.2008.2043. PMID: 18576916

Prognosis

Chau AS, Cole BL, Debley JS, Nanda K, Rosen ABI, Bamshad MJ, Nickerson DA, Torgerson TR, Allenspach EJ
Pediatr Rheumatol Online J 2020 Oct 16;18(1):80. doi: 10.1186/s12969-020-00474-1. PMID: 33066778Free PMC Article
Gill AJ, Kovacsics CE, Vance PJ, Collman RG, Kolson DL
J Virol 2015 Oct;89(20):10656-67. Epub 2015 Aug 12 doi: 10.1128/JVI.01495-15. PMID: 26269184Free PMC Article
Takamiya R, Hung CC, Hall SR, Fukunaga K, Nagaishi T, Maeno T, Owen C, Macias AA, Fredenburgh LE, Ishizaka A, Blumberg RS, Baron RM, Perrella MA
Am J Respir Cell Mol Biol 2009 Aug;41(2):129-35. Epub 2008 Dec 18 doi: 10.1165/rcmb.2008-0331OC. PMID: 19097991Free PMC Article
Ponka P
Semin Hematol 2002 Oct;39(4):249-62. doi: 10.1053/shem.2002.35638. PMID: 12382200
Kawashima A, Oda Y, Yachie A, Koizumi S, Nakanishi I
Hum Pathol 2002 Jan;33(1):125-30. doi: 10.1053/hupa.2002.30217. PMID: 11823983

Clinical prediction guides

Ozen M, Zhao H, Kalish F, Yang Y, Folkins A, Burd I, Wong RJ, Stevenson DK
Am J Reprod Immunol 2018 May;79(5):e12829. Epub 2018 Feb 27 doi: 10.1111/aji.12829. PMID: 29484761
Gill AJ, Kovacsics CE, Vance PJ, Collman RG, Kolson DL
J Virol 2015 Oct;89(20):10656-67. Epub 2015 Aug 12 doi: 10.1128/JVI.01495-15. PMID: 26269184Free PMC Article
Kovtunovych G, Ghosh MC, Ollivierre W, Weitzel RP, Eckhaus MA, Tisdale JF, Yachie A, Rouault TA
Blood 2014 Aug 28;124(9):1522-30. Epub 2014 Jun 24 doi: 10.1182/blood-2014-02-554162. PMID: 24963040Free PMC Article
Radhakrishnan N, Yadav SP, Sachdeva A, Pruthi PK, Sawhney S, Piplani T, Wada T, Yachie A
J Pediatr Hematol Oncol 2011 Jan;33(1):74-8. doi: 10.1097/MPH.0b013e3181fd2aae. PMID: 21088618
Ponka P
Semin Hematol 2002 Oct;39(4):249-62. doi: 10.1053/shem.2002.35638. PMID: 12382200

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