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Sideroblastic anemia 3(SIDBA3)

MedGen UID:
895975
Concept ID:
C4225155
Disease or Syndrome
Synonym: Sideroblastic anemia 3, pyridoxine-refractory
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): GLRX5 (14q32.13)
 
Monarch Initiative: MONDO:0014804
OMIM®: 616860
Orphanet: ORPHA255132

Definition

Sideroblastic anemia-3 is an autosomal recessive hematologic disorder characterized by onset of anemia in adulthood. Affected individuals show signs of systemic iron overload, and iron chelation therapy may be of clinical benefit (summary by Liu et al., 2014). For a discussion of genetic heterogeneity of sideroblastic anemia, see SIDBA1 (300751). [from OMIM]

Clinical features

From HPO
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Hepatosplenomegaly
MedGen UID:
9225
Concept ID:
C0019214
Sign or Symptom
Simultaneous enlargement of the liver and spleen.
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.
Cirrhosis of liver
MedGen UID:
7368
Concept ID:
C0023890
Disease or Syndrome
A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function.
Elevated hepatic iron concentration
MedGen UID:
868497
Concept ID:
C4022891
Finding
An increased level of iron in liver tissues.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Erythroid hyperplasia
MedGen UID:
4536
Concept ID:
C0014800
Disease or Syndrome
Increased count of erythroid precursor cells, that is, erythroid lineage cells in the bone marrow.
Anisocytosis
MedGen UID:
66371
Concept ID:
C0221278
Finding
Abnormally increased variability in the size of erythrocytes.
Hypochromia
MedGen UID:
87187
Concept ID:
C0333912
Finding
A qualitative impression that red blood cells have less color than normal when examined under a microscope, usually related to a reduced amount of hemoglobin in the red blood cells.
Decreased mean corpuscular volume
MedGen UID:
1375398
Concept ID:
C0855790
Finding
A reduction from normal of the mean corpuscular volume, or mean cell volume (MCV) of red blood cells (usually defined as an MCV below 80 femtoliters).
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Type 2 diabetes mellitus
MedGen UID:
41523
Concept ID:
C0011860
Disease or Syndrome
WFS1 spectrum disorder (WFS1-SD) comprises classic WFS1 spectrum disorder and nonclassic WFS1 spectrum disorder. Classic WFS1-SD, a progressive neurodegenerative disorder, is characterized by onset of diabetes mellitus and optic atrophy before age 16 years. Additional complications may include one or more of the following: variable hearing impairment / deafness, diabetes insipidus, neurologic abnormalities, neurogenic bladder, and psychiatric abnormalities. Nonclassic WFS1-SD is less common than classic WFS1-SD. Phenotypes that appear to be milder than classic WFS1-SD include: optic atrophy and hearing impairment; neonatal diabetes, profound congenital deafness, and cataracts; isolated diabetes mellitus; isolated congenital cataracts; and isolated congenital, slowly progressive, and low-frequency (<2000 Hz) sensorineural hearing loss.
Elevated circulating hepatic transaminase concentration
MedGen UID:
116013
Concept ID:
C0235996
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Increased circulating ferritin concentration
MedGen UID:
69130
Concept ID:
C0241013
Finding
Increased concentration of ferritin in the blood circulation.
Conjugated hyperbilirubinemia
MedGen UID:
82787
Concept ID:
C0268307
Disease or Syndrome
Abnormally high level of conjugated bilirubin in the blood.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSideroblastic anemia 3

Professional guidelines

PubMed

Cazzola M
Blood 2022 Apr 21;139(16):2460-2470. doi: 10.1182/blood.2021011045. PMID: 34932791
Patnaik MM, Tefferi A
Am J Hematol 2021 Mar 1;96(3):379-394. Epub 2021 Jan 28 doi: 10.1002/ajh.26090. PMID: 33428785
Massey AC
Med Clin North Am 1992 May;76(3):549-66. doi: 10.1016/s0025-7125(16)30339-x. PMID: 1578956

Recent clinical studies

Etiology

Mangaonkar AA, Lasho TL, Ketterling RP, Reichard KK, Gangat N, Al-Kali A, Begna KH, Pardanani A, Al Ali NH, Talati C, Sallman D, Padron E, Patnaik MM, Tefferi A, Komrokji R
Blood Cancer J 2022 Feb 1;12(2):26. doi: 10.1038/s41408-022-00622-8. PMID: 35105856Free PMC Article
Patnaik MM, Tefferi A
Am J Hematol 2021 Mar 1;96(3):379-394. Epub 2021 Jan 28 doi: 10.1002/ajh.26090. PMID: 33428785
Palmieri F, Scarcia P, Monné M
Biomolecules 2020 Apr 23;10(4) doi: 10.3390/biom10040655. PMID: 32340404Free PMC Article
Fenaux P, Platzbecker U, Mufti GJ, Garcia-Manero G, Buckstein R, Santini V, Díez-Campelo M, Finelli C, Cazzola M, Ilhan O, Sekeres MA, Falantes JF, Arrizabalaga B, Salvi F, Giai V, Vyas P, Bowen D, Selleslag D, DeZern AE, Jurcic JG, Germing U, Götze KS, Quesnel B, Beyne-Rauzy O, Cluzeau T, Voso MT, Mazure D, Vellenga E, Greenberg PL, Hellström-Lindberg E, Zeidan AM, Adès L, Verma A, Savona MR, Laadem A, Benzohra A, Zhang J, Rampersad A, Dunshee DR, Linde PG, Sherman ML, Komrokji RS, List AF
N Engl J Med 2020 Jan 9;382(2):140-151. doi: 10.1056/NEJMoa1908892. PMID: 31914241
Phillips JD
Mol Genet Metab 2019 Nov;128(3):164-177. Epub 2019 Apr 22 doi: 10.1016/j.ymgme.2019.04.008. PMID: 31326287Free PMC Article

Diagnosis

Patnaik MM, Tefferi A
Am J Hematol 2021 Mar 1;96(3):379-394. Epub 2021 Jan 28 doi: 10.1002/ajh.26090. PMID: 33428785
Lefèvre C, Bondu S, Le Goff S, Kosmider O, Fontenay M
Curr Opin Hematol 2017 May;24(3):191-197. doi: 10.1097/MOH.0000000000000325. PMID: 28072603
Finsterer J
Eur J Neurol 2004 Mar;11(3):163-86. doi: 10.1046/j.1351-5101.2003.00728.x. PMID: 15009163
Massey AC
Med Clin North Am 1992 May;76(3):549-66. doi: 10.1016/s0025-7125(16)30339-x. PMID: 1578956
Williams DM
Semin Hematol 1983 Apr;20(2):118-28. PMID: 6410510

Therapy

Patnaik MM, Tefferi A
Am J Hematol 2021 Mar 1;96(3):379-394. Epub 2021 Jan 28 doi: 10.1002/ajh.26090. PMID: 33428785
Fenaux P, Platzbecker U, Mufti GJ, Garcia-Manero G, Buckstein R, Santini V, Díez-Campelo M, Finelli C, Cazzola M, Ilhan O, Sekeres MA, Falantes JF, Arrizabalaga B, Salvi F, Giai V, Vyas P, Bowen D, Selleslag D, DeZern AE, Jurcic JG, Germing U, Götze KS, Quesnel B, Beyne-Rauzy O, Cluzeau T, Voso MT, Mazure D, Vellenga E, Greenberg PL, Hellström-Lindberg E, Zeidan AM, Adès L, Verma A, Savona MR, Laadem A, Benzohra A, Zhang J, Rampersad A, Dunshee DR, Linde PG, Sherman ML, Komrokji RS, List AF
N Engl J Med 2020 Jan 9;382(2):140-151. doi: 10.1056/NEJMoa1908892. PMID: 31914241
Colucci G, Silzle T, Solenthaler M
Am J Hematol 2012 Mar;87(3):305. Epub 2011 Aug 4 doi: 10.1002/ajh.22125. PMID: 21818765
Massey AC
Med Clin North Am 1992 May;76(3):549-66. doi: 10.1016/s0025-7125(16)30339-x. PMID: 1578956
Williams DM
Semin Hematol 1983 Apr;20(2):118-28. PMID: 6410510

Prognosis

Patnaik MM, Tefferi A
Am J Hematol 2021 Mar 1;96(3):379-394. Epub 2021 Jan 28 doi: 10.1002/ajh.26090. PMID: 33428785
Fenaux P, Platzbecker U, Mufti GJ, Garcia-Manero G, Buckstein R, Santini V, Díez-Campelo M, Finelli C, Cazzola M, Ilhan O, Sekeres MA, Falantes JF, Arrizabalaga B, Salvi F, Giai V, Vyas P, Bowen D, Selleslag D, DeZern AE, Jurcic JG, Germing U, Götze KS, Quesnel B, Beyne-Rauzy O, Cluzeau T, Voso MT, Mazure D, Vellenga E, Greenberg PL, Hellström-Lindberg E, Zeidan AM, Adès L, Verma A, Savona MR, Laadem A, Benzohra A, Zhang J, Rampersad A, Dunshee DR, Linde PG, Sherman ML, Komrokji RS, List AF
N Engl J Med 2020 Jan 9;382(2):140-151. doi: 10.1056/NEJMoa1908892. PMID: 31914241
Farruggia P, Di Marco F, Dufour C
Expert Rev Hematol 2018 Mar;11(3):239-246. Epub 2018 Jan 23 doi: 10.1080/17474086.2018.1426454. PMID: 29337599
Malcovati L, Cazzola M
Br J Haematol 2016 Sep;174(6):847-58. Epub 2016 Jul 8 doi: 10.1111/bjh.14215. PMID: 27391606
Finsterer J
Eur J Neurol 2004 Mar;11(3):163-86. doi: 10.1046/j.1351-5101.2003.00728.x. PMID: 15009163

Clinical prediction guides

Fenaux P, Platzbecker U, Mufti GJ, Garcia-Manero G, Buckstein R, Santini V, Díez-Campelo M, Finelli C, Cazzola M, Ilhan O, Sekeres MA, Falantes JF, Arrizabalaga B, Salvi F, Giai V, Vyas P, Bowen D, Selleslag D, DeZern AE, Jurcic JG, Germing U, Götze KS, Quesnel B, Beyne-Rauzy O, Cluzeau T, Voso MT, Mazure D, Vellenga E, Greenberg PL, Hellström-Lindberg E, Zeidan AM, Adès L, Verma A, Savona MR, Laadem A, Benzohra A, Zhang J, Rampersad A, Dunshee DR, Linde PG, Sherman ML, Komrokji RS, List AF
N Engl J Med 2020 Jan 9;382(2):140-151. doi: 10.1056/NEJMoa1908892. PMID: 31914241
Phillips JD
Mol Genet Metab 2019 Nov;128(3):164-177. Epub 2019 Apr 22 doi: 10.1016/j.ymgme.2019.04.008. PMID: 31326287Free PMC Article
Rohr SS, Pelloso LA, Borgo Ados S, de Rezende JG Jr, Silva MR, Yamamoto M, de Lourdes L F Chauffaille M
Med Oncol 2012 Dec;29(5):3570-3. Epub 2012 Jul 4 doi: 10.1007/s12032-012-0297-6. PMID: 22760793
Williams DM
Semin Hematol 1983 Apr;20(2):118-28. PMID: 6410510
Mark J
Adv Cancer Res 1977;24:165-222. doi: 10.1016/s0065-230x(08)61015-5. PMID: 322458

Recent systematic reviews

Maccora I, Ramanan AV, Wiseman D, Marrani E, Mastrolia MV, Simonini G
J Clin Immunol 2023 Jan;43(1):1-30. Epub 2022 Aug 19 doi: 10.1007/s10875-022-01343-0. PMID: 35984545Free PMC Article
Moyo V, Lefebvre P, Duh MS, Yektashenas B, Mundle S
Ann Hematol 2008 Jul;87(7):527-36. Epub 2008 Mar 20 doi: 10.1007/s00277-008-0450-7. PMID: 18351340
Fishman SM, Christian P, West KP
Public Health Nutr 2000 Jun;3(2):125-50. doi: 10.1017/s1368980000000173. PMID: 10948381

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