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Familial hemophagocytic lymphohistiocytosis 3(FHL3)

MedGen UID:
332383
•Concept ID:
C1837174
•
Disease or Syndrome
Synonym: FHL3
 
Gene (location): UNC13D (17q25.1)
 
Monarch Initiative: MONDO:0012146
OMIM®: 608898

Definition

Secretion of the contents of cytolytic granules at the immunologic synapse is a highly regulated process essential for lymphocyte cytotoxicity. This process requires the rapid transfer of perforin (170280)-containing lytic granules to the target cell interface, followed by their docking and fusion with the plasma membrane. Familial hemophagocytic lymphohistiocytosis is a genetically heterogeneous condition characterized by defective cytotoxicity. For a more detailed description of FHL, see 267700. [from OMIM]

Clinical features

From HPO
Hepatosplenomegaly
MedGen UID:
9225
•Concept ID:
C0019214
•
Sign or Symptom
Simultaneous enlargement of the liver and spleen.
See: Feature record | Search on this feature
Anemia
MedGen UID:
1526
•Concept ID:
C0002871
•
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
See: Feature record | Search on this feature
Hypofibrinogenemia
MedGen UID:
107511
•Concept ID:
C0553681
•
Disease or Syndrome
Decreased concentration of fibrinogen in the blood.
See: Feature record | Search on this feature
Hemophagocytosis
MedGen UID:
163750
•Concept ID:
C0876991
•
Disease or Syndrome
Phagocytosis by macrophages of erythrocytes, leukocytes, platelets, and their precursors in bone marrow and other tissues.
See: Feature record | Search on this feature
Reduced natural killer cell activity
MedGen UID:
333452
•Concept ID:
C1839969
•
Finding
Reduced ability of the natural killer cell to function in the adaptive immune response.
See: Feature record | Search on this feature
Granulocytopenia
MedGen UID:
1640845
•Concept ID:
C4551627
•
Disease or Syndrome
An abnormally reduced number of granulocytes in the blood.
See: Feature record | Search on this feature
Fever
MedGen UID:
5169
•Concept ID:
C0015967
•
Sign or Symptom
Body temperature elevated above the normal range.
See: Feature record | Search on this feature
Hypertriglyceridemia
MedGen UID:
167238
•Concept ID:
C0813230
•
Finding
An abnormal increase in the level of triglycerides in the blood.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

A study of ruxolitinib response-based stratified treatment for pediatric hemophagocytic lymphohistiocytosis.
Zhang Q, Zhao YZ, Ma HH, Wang D, Cui L, Li WJ, Wei A, Wang CJ, Wang TY, Li ZG, Zhang R
Blood 2022 Jun 16;139(24):3493-3504. doi: 10.1182/blood.2021014860. PMID: 35344583
The use of anakinra in the treatment of secondary hemophagocytic lymphohistiocytosis.
Bami S, Vagrecha A, Soberman D, Badawi M, Cannone D, Lipton JM, Cron RQ, Levy CF
Pediatr Blood Cancer 2020 Nov;67(11):e28581. Epub 2020 Jul 29 doi: 10.1002/pbc.28581. PMID: 32725881
Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management.
Brudno JN, Kochenderfer JN
Blood Rev 2019 Mar;34:45-55. Epub 2018 Nov 14 doi: 10.1016/j.blre.2018.11.002. PMID: 30528964Free PMC Article

Recent clinical studies

Diagnosis

Detection of a novel gross deletion in the UNC13D gene ends the diagnostic odyssey for a family with familial hemophagocytic lymphohistiocytosis 3.
Nagaraj CB, Brightman DS, Rea H, Wakefield E, Harkavy NVG, Dyer L, Zhang W
BMC Pediatr 2024 Jan 11;24(1):34. doi: 10.1186/s12887-023-04510-3. PMID: 38212754Free PMC Article
Familial Hemophagocytic Lymphohistiocytosis secondary to UNC13D mutation: a report of two cases.
Sadeghi P, Esslami GG, Rokni-Zadeh H, Changi-Ashtiani M, Mohsenipour R
BMC Pediatr 2022 Nov 19;22(1):667. doi: 10.1186/s12887-022-03746-9. PMID: 36401200Free PMC Article
Familial Hemophagocytic Lymphohistiocytosis With Heterozygous STX11 and Homozygous UNC13D Mutations Diagnosed in the Neonatal Period.
Bahadir A, Kader Ş, Çebi AH, Erduran E, Mutlu M, Aslan Y
J Pediatr Hematol Oncol 2022 May 1;44(4):e866-e868. Epub 2022 Mar 16 doi: 10.1097/MPH.0000000000002449. PMID: 35293882
The 253-kb inversion and deep intronic mutations in UNC13D are present in North American patients with familial hemophagocytic lymphohistiocytosis 3.
Qian Y, Johnson JA, Connor JA, Valencia CA, Barasa N, Schubert J, Husami A, Kissell D, Zhang G, Weirauch MT, Filipovich AH, Zhang K
Pediatr Blood Cancer 2014 Jun;61(6):1034-40. Epub 2014 Jan 28 doi: 10.1002/pbc.24955. PMID: 24470399

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