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)

A 60-year-old woman was admitted to our hospital in February 1993 due to dizziness, dyspnea, abdominal pain, and high susceptibility to bleeding. Physical examination revealed livedo reticularis of the foot, but did not detect hepatosplenomegaly. Examination of the peripheral blood detected pancytopenia, leukoerythroblastosis, and tear-drop erythrocytes. Primary myelofibrosis (PMF) was diagnosed on the basis of bone marrow biopsy findings. Antiphospholipid syndrome (APS) was confirmed by positive response to anti-cardiolipin antibody and recurrent splenic infarction. Because of factor XIII deficiency, the patient experienced severe gingival bleeding after tooth extraction. Her condition was complicated by mesenteric arterial thromboembolism and she died of sepsis 5 years after onset. Although the incidence of immunopathy in PMF patients is high, few studies to date have focused on APS patients presenting with a variety of severe embolic symptoms. Our patient required careful monitoring due to bleeding tendency and thromboemboli.
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PMID:[Primary myelofibrosis with fatal mesenteric arterial thromboembolism caused by antiphospholipid syndrome]. 1049 39

Deficiency of adenosine deaminase 2 (DADA2) is a rare autoinflammatory disease that was firstly described in patients with early-onset strokes, livedo reticularis, and periodic fever resembling polyarteritis nodosa. In reported case series, researchers described highly variable manifestations, including autoimmunity, immunodeficiency, hepatosplenomegaly, pancytopenia, ichthyosiform rash, and arthritis, in patients with DADA2. A thirteen-year-old female patient who was born to consanguineous parents was admitted to our hospital with generalized edema and leg pain. A physical examination revealed splenomegaly and left knee arthritis. Nephrotic-range proteinuria and hypoalbuminemia were present, and a renal biopsy revealed amyloidosis. Despite the absence of periodic fever and livedo reticularis, our patient had suggestive features of DADA2, including low serum immunoglobulin G and immunoglobulin M levels, hepatosplenomegaly, and renal amyloidosis. We found a heterozygote Met694Val mutation in the Mediterranean fever gene and a novel homozygote Thr317Argfs*25 (c.950-950delCys) mutation in the cat eye chromosome region 1 gene. A functional analysis revealed absent plasma adenosine deaminase 2 activity. Canakinumab was administered because of unresponsive proteinuria despite 2 months of treatment with colchicine and methylprednisolone. Proteinuria improved after 7 doses of canakinumab. In conclusion, DADA2 should be considered in the differential diagnosis of renal amyloidosis, particularly in the absence of homozygote Mediterranean fever mutations. Although anti-tumor necrosis factor agents are widely offered in DADA2 treatment, we speculate that canakinumab may be an appropriate treatment of renal amyloidosis in DADA2.
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PMID:Renal Amyloidosis in Deficiency of Adenosine Deaminase 2: Successful Experience With Canakinumab. 3037 39

Deficiency of Adenosine Deaminase 2 (DADA2) is a monogenic autoinflammatory disorder characterized by livedo reticularis, skin ulcers, subcutaneous rash, aphthous ulcers, and leukocytoclastic vasculitis, neurological signs such as early onset stroke and polyneuropathy. A minority of DADA2 patients suffer from severe cytopenia and lymphoproliferation. Herein, we report an adolescent patient, followed up as having a hematological disorder for many years, eventually diagnosed as having DADA2. In view of the presence of elevated acute phase reactants, hepatosplenomegaly, low IgM level, lymphopenia, anemia, and neutropenia, and a subtle neurological involvement we considered DADA2 diagnosis. The diagnosis was confirmed by identification of a novel L451W mutation in CECR1 gene. The patient has been successfully treated with etanercept, monthly intravenous immunoglobulin replacement, and low-dose methylprednisolone. In conclusion, although the absence of skin and neurological findings, low IgM levels, and persistent lymphopenia should lead the physicians to consider DADA2 in patients with particularly complicated hematological abnormalities.
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PMID:A homozygote novel L451W mutation in CECR1 gene causes deficiency of adenosine deaminase 2 in a pediatric patient representing with chronic lymphoproliferation and cytopenia. 3152 99

Noonan syndrome-like disorder with loose anagen hair (NS/LAH) is one of the RASopathies, a group of clinically related developmental disorders caused by germline mutations in genes that encode components acting in the RAS/MAPK pathway. Among RASopathies, NS/LAH (OMIM 607721) is an extremely rare, multiple anomaly syndrome characterized by dysmorphic facial features similar to those observed in Noonan syndrome along with some distinctive ectodermal findings including easily pluckable, sparse, thin, and slow-growing hair. ADA2 deficiency (DADA2, OMIM 615688) is a monogenic autoinflammatory disorder caused by homozygous or compound heterozygous mutations in ADA2, with clinical features including recurrent fever, livedo racemosa, hepatosplenomegaly, and strokes as well as immune dysregulation. This is the first report of NS/LAH and ADA2 deficiency in the same individual. We report on a patient presenting with facial features, recurrent infections and ectodermal findings in whom both the clinical and molecular diagnoses of NS/LAH and ADA2 deficiency were established, respectively.
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PMID:ADA2 deficiency in a patient with Noonan syndrome-like disorder with loose anagen hair: The co-occurrence of two rare syndromes. 3158 51