Hemophagocytic Lymphohistiocytosis, Familial, 5, with or without Microvillus Inclusion Disease

Alternative Names

  • FHL5
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WHO-ICD-10 version:2010

Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism

OMIM Number

613101

Mode of Inheritance

Autosomal recessive

Gene Map Locus

19p13.2

Description

Familial hemophagocytic lymphohistiocytosis-5 with or without microvillus inclusion disease (FHL5) is an autosomal recessive hyperinflammatory disorder characterized clinically by fever, hepatosplenomegaly, pancytopenia, coagulation abnormalities, and other laboratory findings. Some patients have neurologic symptoms due to inflammatory CNS disease. There is uncontrolled and ineffective proliferation and activation of T lymphocytes, NK cells, and macrophages that infiltrate multiple organs, including liver, spleen, lymph nodes, and the CNS. The phenotype is variable: some patients may present in early infancy with severe diarrhea, prior to the onset of typical FHL features, whereas others present later in childhood and have a more protracted course without diarrhea. The early-onset diarrhea is due to enteropathy reminiscent of microvillus inclusion disease. The enteropathy, which often necessitates parenteral feeding, may be the most life-threatening issue even after hematopoietic stem cell transplantation (HSCT). More variable features include sensorineural hearing loss and hypogammaglobulinemia. Treatment with immunosuppressive drugs and chemotherapy can ameliorate signs and symptoms of FHL in some patients, but the only curative therapy for FHL is HSCT. HSCT is not curative for enteropathy associated with the disorder, despite hematologic and immunologic reconstitution. [From OMIM]

Epidemiology in the Arab World

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Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
613101.1.1United Arab EmiratesMaleYesYes Abnormal natural killer cell physiology;...NM_006949.4:c.1430C>THomozygousAutosomal, RecessivePagel et al. 2012
613101.1.2United Arab EmiratesMaleYesYes Abnormal natural killer cell physiology;...NM_006949.4:c.1430C>THomozygousAutosomal, RecessivePagel et al. 2012 Brother of 613101.1....
613101.2.1Saudi ArabiaFemaleYesYes Increased circulating antibody levelNM_006949.4:c.1430C>THomozygousAutosomal, RecessivePagel et al. 2012; zur Stadt et al. 2009
613101.2.2Saudi ArabiaMaleYesYes Immune dysregulationNM_006949.4:c.1430C>THomozygousAutosomal, RecessivePagel et al. 2012 Brother of 613101.2....
613101.3United Arab EmiratesMaleYesYes Abnormal natural killer cell physiology;...NM_006949.4:c.1430C>THomozygousAutosomal, RecessivePagel et al. 2012
613101.4.1LebanonFemaleYesYes Abnormal natural killer cell physiology;...NM_006949.4:c.1727delHomozygousAutosomal, RecessivePagel et al. 2012
613101.4.2LebanonFemaleYesYes Abnormal natural killer cell physiology;...NM_006949.4:c.1727delHomozygousAutosomal, RecessivePagel et al. 2012 Sister of 613101.4.1

Other Reports

United Arab Emirates

In a retrospective study, Awan et al. 2013 analysed case histories of ten patients with hemophagocytic lymphohistiocytosis (HLH) seen at Pediatric Hematology/Oncology in Tawam Hospital, UAE between 2006 and 2012. All patients had prolonged fever, splenomegaly, and cytopenia, and 50% of patients displayed central nervous system-related symptoms. An Emirati patient (male, 3 years) was identified with mutation in STXBP2  gene, which is associated with hemophagocytic lymphohistiocytosis, familial, 5, with or without microvillus inclusion disease.

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