Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Omenn syndrome (OS) is a rare disorder within the combined immunodeficiency family that is characterized by a diffuse exudative, erythematous rash, lymphadenopathy, hepatosplenomegaly, alopecia, and failure to thrive. Specific lab findings unique to OS include hypereosinophilia, elevated IgE, excess production of oligoclonal T-cells and near-to-absent B-cells. Much remains elucidated about the underlying genetic cause of OS. Until recently, it was felt that the disease was primarily caused by mutations of the RAG1 or RAG2 genes. The type of mutation of the RAG1 and RAG2 genes in patients with OS affects the degree of functioning variable (diversity) joining [V(D)J] recombination activity, which is critical to the development of lymphoid cell receptor diversity. New work has also shown that thymic tissue in OS patients demonstrates a severe defect in the expression of the autoimmune regulator element. This may contribute to the development of autoreactive T-cells that are felt to be the causative agent of a number of the clinical hallmarks unique to OS. The genetic spectrum of OS was further expanded when a patient with clinical and immunologic features consistent with OS, without RAG mutation, was found to have mutations in both alleles coding for ARTEMIS, a key V(D)J recombination/DNA repair factor. Regardless of the underlying cause, early recognition is critical because patients die at a very young age without bone marrow transplantation. We describe an infant diagnosed with OS post-mortem in which death was directly related to the development of necrotizing enterocolitis.
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PMID:Necrotizing enterocolitis in an infant with Omenn syndrome. 1717 92

Autoinflammatory diseases are caused by pathologic activation of the innate immune system. Primary hemophagocytic lymphohistiocytosis (HLH) is an aggressive syndrome of excessive immune activation caused by monogenic mutations resulting in cytotoxic cell defects and subsequent failure to eliminate activated macrophages. Secondary HLH is often diagnosed in cases without a known Mendelian inheritance. However, some cases of "secondary" HLH have been shown to harbor mutations with partial dysfunction of the cytotoxic system. Recently, macrophage intrinsic abnormalities caused by NLRC4 inflammasome mutations have been linked to autoinflammation and recurrent macrophage activation syndromes resembling a primary HLH. We report a case of a former 28-week preterm infant with congenital anemia, ascites, and a heavy edematous placenta with fetal thrombotic vasculopathy, who developed hepatosplenomegaly and unexplained systemic inflammation with laboratory features of HLH in the early postnatal course and died at 2 months of age. Postmortem examination confirmed the hepatosplenomegaly with marked sinusoidal hemophagocytosis, along with striking hemophagocytosis in the bone marrow and lymph nodes. There was extensive acute and chronic ischemic bowel disease with matted bowel loops, fibrous adhesions, and patchy necrotizing enterocolitis features. Whole exome sequencing analysis demonstrated a novel mosaic heterozygous NLRC4 512 C> T (p.Ser171Phe) de novo mutation predicated to cause a dominant, gain-of-function mutation resulting in a constitutively active protein. The assembly of NLRC4-containing inflammasomes via an induced self-propagation mechanism likely enables a perpetuating process of systemic macrophage activation, presumed to be initiated in utero in this patient.
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PMID:Novel NLRC4 Mutation Causes a Syndrome of Perinatal Autoinflammation With Hemophagocytic Lymphohistiocytosis, Hepatosplenomegaly, Fetal Thrombotic Vasculopathy, and Congenital Anemia and Ascites. 2840 91