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UNC13D Deficiency

MedGen UID:
925612
•Concept ID:
C4288080
•
Disease or Syndrome
Synonym: MUNC13-4 Deficiency

Definition

A condition of decreased or absent presence of protein unc-13 homolog D. Deficiency of this protein is associated with familial hemophagocytic lymphohistiocytosis 3. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVUNC13D Deficiency

Professional guidelines

PubMed

Genotype characteristics and immunological indicator evaluation of 311 hemophagocytic lymphohistiocytosis cases in China.
Zhang J, Sun Y, Shi X, Zhang R, Wang Y, Xiao J, Cao J, Gao Z, Wang J, Wu L, Wei W, Wang Z
Orphanet J Rare Dis 2020 May 6;15(1):112. doi: 10.1186/s13023-020-01390-z. PMID: 32375849Free PMC Article
Perforin and CD107a testing is superior to NK cell function testing for screening patients for genetic HLH.
Rubin TS, Zhang K, Gifford C, Lane A, Choo S, Bleesing JJ, Marsh RA
Blood 2017 Jun 1;129(22):2993-2999. Epub 2017 Mar 7 doi: 10.1182/blood-2016-12-753830. PMID: 28270454Free PMC Article
Combined newborn screening for familial hemophagocytic lymphohistiocytosis and severe T- and B-cell immunodeficiencies.
Borte S, Meeths M, Liebscher I, Krist K, Nordenskjöld M, Hammarström L, von Döbeln U, Henter JI, Bryceson YT
J Allergy Clin Immunol 2014 Jul;134(1):226-8. Epub 2014 May 29 doi: 10.1016/j.jaci.2014.04.026. PMID: 24882743

Recent clinical studies

Etiology

Primary immune regulatory disorders (PIRD): expanding the mutation spectrum in Turkey and identification of sixteen novel variants.
Aykut A, Durmaz A, Karaca N, Gulez N, Genel F, Celmeli F, Cogurlu MT, Akcan M, Cicek D, Cipe FE, Kiykim A, Yıldıran A, Unluhizarci K, Kilic SS, Aksu G, Ardeniz O, Kutukculer N
Immunol Res 2024 Aug;72(4):714-726. Epub 2024 Apr 22 doi: 10.1007/s12026-024-09477-6. PMID: 38644452Free PMC Article
Clinical, immunological and genetic findings in patients with UNC13D deficiency (FHL3): A systematic review.
Amirifar P, Ranjouri MR, Abolhassani H, Moeini Shad T, Almasi-Hashiani A, Azizi G, Moamer S, Aghamohammadi A, Yazdani R
Pediatr Allergy Immunol 2021 Jan;32(1):186-197. Epub 2020 Aug 24 doi: 10.1111/pai.13323. PMID: 32679608
Genotype characteristics and immunological indicator evaluation of 311 hemophagocytic lymphohistiocytosis cases in China.
Zhang J, Sun Y, Shi X, Zhang R, Wang Y, Xiao J, Cao J, Gao Z, Wang J, Wu L, Wei W, Wang Z
Orphanet J Rare Dis 2020 May 6;15(1):112. doi: 10.1186/s13023-020-01390-z. PMID: 32375849Free PMC Article
Primary Immunodeficiencies Associated with EBV Disease.
Cohen JI
Curr Top Microbiol Immunol 2015;390(Pt 1):241-65. doi: 10.1007/978-3-319-22822-8_10. PMID: 26424649Free PMC Article
Familial hemophagocytic lymphohistiocytosis: a model for understanding the human machinery of cellular cytotoxicity.
Sieni E, Cetica V, Mastrodicasa E, Pende D, Moretta L, Griffiths G, Aricò M
Cell Mol Life Sci 2012 Jan;69(1):29-40. Epub 2011 Oct 12 doi: 10.1007/s00018-011-0835-y. PMID: 21990010Free PMC Article

Diagnosis

Clinical, immunological and genetic findings in patients with UNC13D deficiency (FHL3): A systematic review.
Amirifar P, Ranjouri MR, Abolhassani H, Moeini Shad T, Almasi-Hashiani A, Azizi G, Moamer S, Aghamohammadi A, Yazdani R
Pediatr Allergy Immunol 2021 Jan;32(1):186-197. Epub 2020 Aug 24 doi: 10.1111/pai.13323. PMID: 32679608
Frequency and spectrum of disease-causing variants in 1892 patients with suspected genetic HLH disorders.
Gadoury-Levesque V, Dong L, Su R, Chen J, Zhang K, Risma KA, Marsh RA, Sun M
Blood Adv 2020 Jun 23;4(12):2578-2594. doi: 10.1182/bloodadvances.2020001605. PMID: 32542393Free PMC Article
Pediatric hemophagocytic lymphohistiocytosis.
Canna SW, Marsh RA
Blood 2020 Apr 16;135(16):1332-1343. doi: 10.1182/blood.2019000936. PMID: 32107531Free PMC Article
Clinical and Genetic Analysis of Nine Suspected Familial Haemophagocytic Lymphohistiocytosis Patients for MUNC13-4 Deficiency and Introducing Four Novel Mutations in UNC13D.
Vahidi M, Badalzadeh M, Jannesar M, Mazinani M, Fazlollahi MR, Khodayari Namini N, Houshmand M, Hamidieh AA, Moradi L, Pourpak Z, Moin M
Iran J Allergy Asthma Immunol 2019 Oct 23;18(5):487-492. doi: 10.18502/ijaai.v18i5.1911. PMID: 32245292
Cross-regulation of defective endolysosome trafficking and enhanced autophagy through TFEB in UNC13D deficiency.
Zhang J, He J, Johnson JL, Napolitano G, Ramadass M, Rahman F, Catz SD
Autophagy 2019 Oct;15(10):1738-1756. Epub 2019 Apr 5 doi: 10.1080/15548627.2019.1596475. PMID: 30892133Free PMC Article

Therapy

Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis.
Blincoe A, Heeg M, Campbell PK, Hines M, Khojah A, Klein-Gitelman M, Talano JA, Speckmann C, Touzot F, Lankester A, Legger GE, Rivière JG, Garcia-Prat M, Alonso L, Putti MC, Lehmberg K, Maier S, El Chazli Y, Elmaksoud MA, Astigarraga I, Kurjane N, Bulina I, Kenina V, Bryceson Y, Rascon J, Lortie A, Goldstein G, Booth C, Worth A, Wassmer E, Schmitt EG, Warren JT, Bednarski JJ, Ali S, Chiang KY, Krueger J, Henry MM, Holland SM, Marsh RA, Ehl S, Haddad E
J Clin Immunol 2020 Aug;40(6):901-916. Epub 2020 Jul 7 doi: 10.1007/s10875-020-00814-6. PMID: 32638196
Application of blood and immunodeficiency gene detection in the diagnosis of hemophagocytic lymphohistiocytosis patients.
Mo W, Wei W, Sun Y, Yang Y, Guan Z, Li M, Zhu P, Chi Z
Exp Hematol 2019 Oct;78:62-69. Epub 2019 Sep 25 doi: 10.1016/j.exphem.2019.09.024. PMID: 31562900
UNC13D Deficiency Associated With Epileptic Seizures and Antibody Deficiency: The First Case from the Iranian National Registry.
Yazdani R, Amirifar P, Abolhassani H, Azizi G, Parvaneh N, Rezaei N, Aghamohammadi A
J Investig Allergol Clin Immunol 2019 Apr;29(2):160-162. doi: 10.18176/jiaci.0362. PMID: 31017122
Rotavirus-associated hemophagocytic lymphohistiocytosis (HLH) after hematopoietic stem cell transplantation for familial HLH.
Park M, Yun YJ, Woo SI, Lee JW, Chung NG, Cho B
Pediatr Int 2015 Apr;57(2):e77-80. Epub 2015 Feb 24 doi: 10.1111/ped.12567. PMID: 25712613

Prognosis

Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis.
Blincoe A, Heeg M, Campbell PK, Hines M, Khojah A, Klein-Gitelman M, Talano JA, Speckmann C, Touzot F, Lankester A, Legger GE, Rivière JG, Garcia-Prat M, Alonso L, Putti MC, Lehmberg K, Maier S, El Chazli Y, Elmaksoud MA, Astigarraga I, Kurjane N, Bulina I, Kenina V, Bryceson Y, Rascon J, Lortie A, Goldstein G, Booth C, Worth A, Wassmer E, Schmitt EG, Warren JT, Bednarski JJ, Ali S, Chiang KY, Krueger J, Henry MM, Holland SM, Marsh RA, Ehl S, Haddad E
J Clin Immunol 2020 Aug;40(6):901-916. Epub 2020 Jul 7 doi: 10.1007/s10875-020-00814-6. PMID: 32638196
Genotype characteristics and immunological indicator evaluation of 311 hemophagocytic lymphohistiocytosis cases in China.
Zhang J, Sun Y, Shi X, Zhang R, Wang Y, Xiao J, Cao J, Gao Z, Wang J, Wu L, Wei W, Wang Z
Orphanet J Rare Dis 2020 May 6;15(1):112. doi: 10.1186/s13023-020-01390-z. PMID: 32375849Free PMC Article
Clinical and Genetic Analysis of Nine Suspected Familial Haemophagocytic Lymphohistiocytosis Patients for MUNC13-4 Deficiency and Introducing Four Novel Mutations in UNC13D.
Vahidi M, Badalzadeh M, Jannesar M, Mazinani M, Fazlollahi MR, Khodayari Namini N, Houshmand M, Hamidieh AA, Moradi L, Pourpak Z, Moin M
Iran J Allergy Asthma Immunol 2019 Oct 23;18(5):487-492. doi: 10.18502/ijaai.v18i5.1911. PMID: 32245292
Atypical familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D and STXBP2 overlaps with primary immunodeficiency diseases.
Rohr J, Beutel K, Maul-Pavicic A, Vraetz T, Thiel J, Warnatz K, Bondzio I, Gross-Wieltsch U, Schündeln M, Schütz B, Woessmann W, Groll AH, Strahm B, Pagel J, Speckmann C, Janka G, Griffiths G, Schwarz K, zur Stadt U, Ehl S
Haematologica 2010 Dec;95(12):2080-7. Epub 2010 Sep 7 doi: 10.3324/haematol.2010.029389. PMID: 20823128Free PMC Article
Correlation between phenotypic heterogeneity and gene mutational characteristics in familial hemophagocytic lymphohistiocytosis (FHL).
Ueda I, Ishii E, Morimoto A, Ohga S, Sako M, Imashuku S
Pediatr Blood Cancer 2006 Apr;46(4):482-8. doi: 10.1002/pbc.20511. PMID: 16365863

Clinical prediction guides

Frequency and spectrum of disease-causing variants in 1892 patients with suspected genetic HLH disorders.
Gadoury-Levesque V, Dong L, Su R, Chen J, Zhang K, Risma KA, Marsh RA, Sun M
Blood Adv 2020 Jun 23;4(12):2578-2594. doi: 10.1182/bloodadvances.2020001605. PMID: 32542393Free PMC Article
Genotype characteristics and immunological indicator evaluation of 311 hemophagocytic lymphohistiocytosis cases in China.
Zhang J, Sun Y, Shi X, Zhang R, Wang Y, Xiao J, Cao J, Gao Z, Wang J, Wu L, Wei W, Wang Z
Orphanet J Rare Dis 2020 May 6;15(1):112. doi: 10.1186/s13023-020-01390-z. PMID: 32375849Free PMC Article
Clinical and Genetic Analysis of Nine Suspected Familial Haemophagocytic Lymphohistiocytosis Patients for MUNC13-4 Deficiency and Introducing Four Novel Mutations in UNC13D.
Vahidi M, Badalzadeh M, Jannesar M, Mazinani M, Fazlollahi MR, Khodayari Namini N, Houshmand M, Hamidieh AA, Moradi L, Pourpak Z, Moin M
Iran J Allergy Asthma Immunol 2019 Oct 23;18(5):487-492. doi: 10.18502/ijaai.v18i5.1911. PMID: 32245292
STX11 mutations and clinical phenotypes of familial hemophagocytic lymphohistiocytosis in North America.
Marsh RA, Satake N, Biroschak J, Jacobs T, Johnson J, Jordan MB, Bleesing JJ, Filipovich AH, Zhang K
Pediatr Blood Cancer 2010 Jul 15;55(1):134-40. doi: 10.1002/pbc.22499. PMID: 20486178
Defective cytotoxic lymphocyte degranulation in syntaxin-11 deficient familial hemophagocytic lymphohistiocytosis 4 (FHL4) patients.
Bryceson YT, Rudd E, Zheng C, Edner J, Ma D, Wood SM, Bechensteen AG, Boelens JJ, Celkan T, Farah RA, Hultenby K, Winiarski J, Roche PA, Nordenskjöld M, Henter JI, Long EO, Ljunggren HG
Blood 2007 Sep 15;110(6):1906-15. Epub 2007 May 24 doi: 10.1182/blood-2007-02-074468. PMID: 17525286Free PMC Article

Recent systematic reviews

Clinical, immunological and genetic findings in patients with UNC13D deficiency (FHL3): A systematic review.
Amirifar P, Ranjouri MR, Abolhassani H, Moeini Shad T, Almasi-Hashiani A, Azizi G, Moamer S, Aghamohammadi A, Yazdani R
Pediatr Allergy Immunol 2021 Jan;32(1):186-197. Epub 2020 Aug 24 doi: 10.1111/pai.13323. PMID: 32679608

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