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Thrombocytopenia 13, syndromic(THC13)

MedGen UID:
1856296
Concept ID:
C5935599
Disease or Syndrome
Synonym: THROMBOCYTOPENIA, AUTOSOMAL RECESSIVE, 13
 
Gene (location): GALE (1p36.11)
 
Monarch Initiative: MONDO:0958333
OMIM®: 620776

Definition

Syndromic thrombocytopenia-13 (THC13) is an autosomal recessive disorder characterized mainly by congenital thrombocytopenia resulting in increased bleeding. Platelets tend to be enlarged (macrothrombocytopenia) and/or gray and show functional defects. Some patients have infection-induced leukopenia or anemia and pancytopenia. Additional more variable features have also been reported, including mitral valve malformations, pyloric stenosis, and impaired intellectual development (Seo et al., 2019; Febres-Aldana et al., 2020; Marin-Quilez et al., 2023). For a discussion of genetic heterogeneity of thrombocytopenia, see THC1 (313900). [from OMIM]

Clinical features

From HPO
Mitral valve prolapse
MedGen UID:
7671
Concept ID:
C0026267
Disease or Syndrome
One or both of the leaflets (cusps) of the mitral valve bulges back into the left atrium upon contraction of the left ventricle.
Tricuspid valve prolapse
MedGen UID:
11912
Concept ID:
C0040962
Disease or Syndrome
One or more of the leaflets (cusps) of the tricuspid valve bulges back into the right atrium upon contraction of the right ventricle.
Cerebral hemorrhage
MedGen UID:
423648
Concept ID:
C2937358
Pathologic Function
Hemorrhage into the parenchyma of the brain.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Congenital hypertrophic pyloric stenosis
MedGen UID:
196010
Concept ID:
C0700639
Congenital Abnormality
Pyloric stenosis, also known as infantile hypertrophic pyloric stenosis, is an uncommon condition in infants characterized by abnormal thickening of the pylorus muscles in the stomach leading to gastric outlet obstruction. Clinically infants are well at birth. Then, at 3 to 6 weeks of age, the infants present with projectile vomiting, potentially leading to dehydration and weight loss.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Epistaxis
MedGen UID:
4996
Concept ID:
C0014591
Pathologic Function
Epistaxis, or nosebleed, refers to a hemorrhage localized in the nose.
Gingival bleeding
MedGen UID:
42218
Concept ID:
C0017565
Pathologic Function
Hemorrhage affecting the gingiva.
Pancytopenia
MedGen UID:
18281
Concept ID:
C0030312
Disease or Syndrome
An abnormal reduction in numbers of all blood cell types (red blood cells, white blood cells, and platelets).
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Reticulocytosis
MedGen UID:
60089
Concept ID:
C0206160
Finding
An elevation in the number of reticulocytes (immature erythrocytes) in the peripheral blood circulation.
Giant platelets
MedGen UID:
137700
Concept ID:
C0333864
Finding
Giant platelets are larger than 7 micrometers and usually 10 to 20 micrometers. The term giant platelet is used when the platelet is larger than the size of the average red cell in the field. (Description adapted from College of American Pathologists, Hematology Manual, 1998).
Abnormal bleeding
MedGen UID:
264316
Concept ID:
C1458140
Pathologic Function
An abnormal susceptibility to bleeding, often referred to as a bleeding diathesis. A bleeding diathesis may be related to vascular, platelet and coagulation defects.
Bone marrow hypocellularity
MedGen UID:
383749
Concept ID:
C1855710
Finding
A reduced number of hematopoietic cells present in the bone marrow relative to marrow fat.
Macrothrombocytopenia
MedGen UID:
414334
Concept ID:
C2751260
Disease or Syndrome
Megakaryocyte nucleus hypolobulation
MedGen UID:
1614231
Concept ID:
C4531162
Finding
The presence of megakaryocytes in the bone marrow whose nuclei are less lobulated than expected for the size of the nucleus.
Megakaryocyte dysplasia
MedGen UID:
1611304
Concept ID:
C4540467
Finding
The presence of micro-megakaryocytes, hypo-lobed, or non-lobed nuclei in megakaryocytes of all sizes and multiple, widely-separated nuclei.
Leukopenia
MedGen UID:
6073
Concept ID:
C0023530
Disease or Syndrome
An abnormal decreased number of leukocytes in the blood.
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Antinuclear antibody positivity
MedGen UID:
101792
Concept ID:
C0151480
Laboratory or Test Result
The presence of autoantibodies in the serum that react against nuclei or nuclear components.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Hypergalactosemia
MedGen UID:
892325
Concept ID:
C4023071
Finding
Elevated concentration of galactose in the blood.
Reduced erythrocyte galactose-1-phosphate uridylyltransferase activity
MedGen UID:
1853189
Concept ID:
C5872957
Finding
Activity or concentration of in the level of galactose-1-phosphate uridylyltransferase (GALT; EC 2.7.7.12) in erythrocytes below the lower limit of normal.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.

Professional guidelines

PubMed

Fattizzo B, Marchetti M, Michel M, Cantoni S, Frederiksen H, Giordano G, Glenthøj A, González-López TJ, Murakhovskaya I, Napolitano M, Mingot ME, Arguello M, Patriarca A, Raso S, Vianelli N, Barcellini W
Lancet Haematol 2024 Aug;11(8):e617-e628. Epub 2024 Jul 2 doi: 10.1016/S2352-3026(24)00144-3. PMID: 38968944
Sciascia S, Amigo MC, Roccatello D, Khamashta M
Nat Rev Rheumatol 2017 Sep;13(9):548-560. Epub 2017 Aug 3 doi: 10.1038/nrrheum.2017.124. PMID: 28769114
Carson JL, Guyatt G, Heddle NM, Grossman BJ, Cohn CS, Fung MK, Gernsheimer T, Holcomb JB, Kaplan LJ, Katz LM, Peterson N, Ramsey G, Rao SV, Roback JD, Shander A, Tobian AA
JAMA 2016 Nov 15;316(19):2025-2035. doi: 10.1001/jama.2016.9185. PMID: 27732721

Recent clinical studies

Etiology

Platzbecker U, Santini V, Fenaux P, Sekeres MA, Savona MR, Madanat YF, Díez-Campelo M, Valcárcel D, Illmer T, Jonášová A, Bělohlávková P, Sherman LJ, Berry T, Dougherty S, Shah S, Xia Q, Sun L, Wan Y, Huang F, Ikin A, Navada S, Feller F, Komrokji RS, Zeidan AM
Lancet 2024 Jan 20;403(10423):249-260. Epub 2023 Dec 1 doi: 10.1016/S0140-6736(23)01724-5. PMID: 38048786
Sehgal A, Hoda D, Riedell PA, Ghosh N, Hamadani M, Hildebrandt GC, Godwin JE, Reagan PM, Wagner-Johnston N, Essell J, Nath R, Solomon SR, Champion R, Licitra E, Fanning S, Gupta N, Dubowy R, D'Andrea A, Wang L, Ogasawara K, Thorpe J, Gordon LI
Lancet Oncol 2022 Aug;23(8):1066-1077. Epub 2022 Jul 12 doi: 10.1016/S1470-2045(22)00339-4. PMID: 35839786
Kamdar M, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, Ibrahimi S, Mielke S, Mutsaers P, Hernandez-Ilizaliturri F, Izutsu K, Morschhauser F, Lunning M, Maloney DG, Crotta A, Montheard S, Previtali A, Stepan L, Ogasawara K, Mack T, Abramson JS; TRANSFORM Investigators
Lancet 2022 Jun 18;399(10343):2294-2308. doi: 10.1016/S0140-6736(22)00662-6. PMID: 35717989
Brocklebank V, Wood KM, Kavanagh D
Clin J Am Soc Nephrol 2018 Feb 7;13(2):300-317. Epub 2017 Oct 17 doi: 10.2215/CJN.00620117. PMID: 29042465Free PMC Article
Kremer Hovinga JA, Coppo P, Lämmle B, Moake JL, Miyata T, Vanhoorelbeke K
Nat Rev Dis Primers 2017 Apr 6;3:17020. doi: 10.1038/nrdp.2017.20. PMID: 28382967

Diagnosis

Cavero T, Auñón P, Caravaca-Fontán F, Trujillo H, Arjona E, Morales E, Guillén E, Blasco M, Rabasco C, Espinosa M, Blanco M, Rodríguez-Magariños C, Cao M, Ávila A, Huerta A, Rubio E, Cabello V, Barros X, Goicoechea de Jorge E, Rodríguez de Córdoba S, Praga M
Nephrol Dial Transplant 2023 May 4;38(5):1217-1226. doi: 10.1093/ndt/gfac248. PMID: 36002030
Palma LMP, Vaisbich-Guimarães MH, Sridharan M, Tran CL, Sethi S
Pediatr Nephrol 2022 Sep;37(9):1967-1980. Epub 2022 Jan 18 doi: 10.1007/s00467-021-05370-8. PMID: 35041041Free PMC Article
Society for Maternal-Fetal Medicine (SMFM), Gandhi M, Rac MWF, McKinney J
Am J Obstet Gynecol 2019 Dec;221(6):B16-B18. doi: 10.1016/j.ajog.2019.09.024. PMID: 31787159
Brocklebank V, Wood KM, Kavanagh D
Clin J Am Soc Nephrol 2018 Feb 7;13(2):300-317. Epub 2017 Oct 17 doi: 10.2215/CJN.00620117. PMID: 29042465Free PMC Article
Kremer Hovinga JA, Coppo P, Lämmle B, Moake JL, Miyata T, Vanhoorelbeke K
Nat Rev Dis Primers 2017 Apr 6;3:17020. doi: 10.1038/nrdp.2017.20. PMID: 28382967

Therapy

Platzbecker U, Santini V, Fenaux P, Sekeres MA, Savona MR, Madanat YF, Díez-Campelo M, Valcárcel D, Illmer T, Jonášová A, Bělohlávková P, Sherman LJ, Berry T, Dougherty S, Shah S, Xia Q, Sun L, Wan Y, Huang F, Ikin A, Navada S, Feller F, Komrokji RS, Zeidan AM
Lancet 2024 Jan 20;403(10423):249-260. Epub 2023 Dec 1 doi: 10.1016/S0140-6736(23)01724-5. PMID: 38048786
Kamdar M, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, Ibrahimi S, Mielke S, Mutsaers P, Hernandez-Ilizaliturri F, Izutsu K, Morschhauser F, Lunning M, Maloney DG, Crotta A, Montheard S, Previtali A, Stepan L, Ogasawara K, Mack T, Abramson JS; TRANSFORM Investigators
Lancet 2022 Jun 18;399(10343):2294-2308. doi: 10.1016/S0140-6736(22)00662-6. PMID: 35717989
Asakura H, Ogawa H
Int J Hematol 2021 Jan;113(1):45-57. Epub 2020 Nov 7 doi: 10.1007/s12185-020-03029-y. PMID: 33161508Free PMC Article
Brocklebank V, Wood KM, Kavanagh D
Clin J Am Soc Nephrol 2018 Feb 7;13(2):300-317. Epub 2017 Oct 17 doi: 10.2215/CJN.00620117. PMID: 29042465Free PMC Article
Kremer Hovinga JA, Coppo P, Lämmle B, Moake JL, Miyata T, Vanhoorelbeke K
Nat Rev Dis Primers 2017 Apr 6;3:17020. doi: 10.1038/nrdp.2017.20. PMID: 28382967

Prognosis

Fattizzo B, Marchetti M, Michel M, Cantoni S, Frederiksen H, Giordano G, Glenthøj A, González-López TJ, Murakhovskaya I, Napolitano M, Mingot ME, Arguello M, Patriarca A, Raso S, Vianelli N, Barcellini W
Lancet Haematol 2024 Aug;11(8):e617-e628. Epub 2024 Jul 2 doi: 10.1016/S2352-3026(24)00144-3. PMID: 38968944
Platzbecker U, Santini V, Fenaux P, Sekeres MA, Savona MR, Madanat YF, Díez-Campelo M, Valcárcel D, Illmer T, Jonášová A, Bělohlávková P, Sherman LJ, Berry T, Dougherty S, Shah S, Xia Q, Sun L, Wan Y, Huang F, Ikin A, Navada S, Feller F, Komrokji RS, Zeidan AM
Lancet 2024 Jan 20;403(10423):249-260. Epub 2023 Dec 1 doi: 10.1016/S0140-6736(23)01724-5. PMID: 38048786
Asakura H, Ogawa H
Int J Hematol 2021 Jan;113(1):45-57. Epub 2020 Nov 7 doi: 10.1007/s12185-020-03029-y. PMID: 33161508Free PMC Article
Brocklebank V, Wood KM, Kavanagh D
Clin J Am Soc Nephrol 2018 Feb 7;13(2):300-317. Epub 2017 Oct 17 doi: 10.2215/CJN.00620117. PMID: 29042465Free PMC Article
Kathiresan S, Shiomura J, Jang IK
J Thromb Thrombolysis 2002 Feb;13(1):41-7. doi: 10.1023/a:1015368126304. PMID: 11994559

Clinical prediction guides

Platzbecker U, Santini V, Fenaux P, Sekeres MA, Savona MR, Madanat YF, Díez-Campelo M, Valcárcel D, Illmer T, Jonášová A, Bělohlávková P, Sherman LJ, Berry T, Dougherty S, Shah S, Xia Q, Sun L, Wan Y, Huang F, Ikin A, Navada S, Feller F, Komrokji RS, Zeidan AM
Lancet 2024 Jan 20;403(10423):249-260. Epub 2023 Dec 1 doi: 10.1016/S0140-6736(23)01724-5. PMID: 38048786
Beck DB, Bodian DL, Shah V, Mirshahi UL, Kim J, Ding Y, Magaziner SJ, Strande NT, Cantor A, Haley JS, Cook A, Hill W, Schwartz AL, Grayson PC, Ferrada MA, Kastner DL, Carey DJ, Stewart DR
JAMA 2023 Jan 24;329(4):318-324. doi: 10.1001/jama.2022.24836. PMID: 36692560Free PMC Article
Kamdar M, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, Ibrahimi S, Mielke S, Mutsaers P, Hernandez-Ilizaliturri F, Izutsu K, Morschhauser F, Lunning M, Maloney DG, Crotta A, Montheard S, Previtali A, Stepan L, Ogasawara K, Mack T, Abramson JS; TRANSFORM Investigators
Lancet 2022 Jun 18;399(10343):2294-2308. doi: 10.1016/S0140-6736(22)00662-6. PMID: 35717989
Schaefer F, Ardissino G, Ariceta G, Fakhouri F, Scully M, Isbel N, Lommelé Å, Kupelian V, Gasteyger C, Greenbaum LA, Johnson S, Ogawa M, Licht C, Vande Walle J, Frémeaux-Bacchi V; Global aHUS Registry
Kidney Int 2018 Aug;94(2):408-418. Epub 2018 Jun 19 doi: 10.1016/j.kint.2018.02.029. PMID: 29907460
Kathiresan S, Shiomura J, Jang IK
J Thromb Thrombolysis 2002 Feb;13(1):41-7. doi: 10.1023/a:1015368126304. PMID: 11994559

Recent systematic reviews

Meng F, Xiang M, Liu Y, Zeng D
BMC Cancer 2025 Jan 14;25(1):78. doi: 10.1186/s12885-024-13400-5. PMID: 39806291Free PMC Article
Golub D, McBriar JD, Donaldson H, Wong T, Unadkat P, White TG, Quach ET, Haddock S, Chitti B, Ziemba Y, Goenka A, Singer S, Schulder M, Dehdashti AR
J Neurooncol 2023 Nov;165(2):229-239. Epub 2023 Nov 13 doi: 10.1007/s11060-023-04499-w. PMID: 37955760
Mossayebi MH, Iyer NS, McLaren RA Jr, Moussa HN, Sibai BM, Al-Kouatly HB
Am J Obstet Gynecol 2023 Nov;229(5):502-515.e10. Epub 2023 May 5 doi: 10.1016/j.ajog.2023.04.046. PMID: 37150281
Raina R, Sethi SK, Dragon-Durey MA, Khooblall A, Sharma D, Khandelwal P, Shapiro R, Boyer O, Yap HK, Bagga A, Licht C
Pediatr Nephrol 2022 Jul;37(7):1479-1493. Epub 2022 Feb 3 doi: 10.1007/s00467-022-05451-2. PMID: 35118546
Yue J, Dong BR, Yang M, Chen X, Wu T, Liu GJ
Cochrane Database Syst Rev 2016 Jan 7;2016(1):CD008056. doi: 10.1002/14651858.CD008056.pub3. PMID: 26758498Free PMC Article

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