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)

Congenital erythropoietic porphyria (CEP) is a rare disorder of heme biosynthesis. Skeletal abnormalities have been described in patients with this disease. We report a 25-year-old woman with osteodystrophy from CEP. On examination, mild hepatosplenomegaly, multiple hyperpigmented scars, hypertrichosis, erythrodontia and red coloration of urine were found. Biochemical studies showed increased serum levels of alkaline phosphatase, fasting and total 24-h urinary calcium excretion. Serum 250H vitamin-D concentration was low due to avoidance of sun exposure. Skeletal radiographs disclosed marked vertical and horizontal trabecular pattern and biconcavity of most of the dorsal and lumbar vertebral bodies. Several round sclerotic lesions (1-3 cm in diameter) were seen in the skull, pelvis and one lumbar vertebrae. The sclerotic lesions were augmented in size and number compared to X-rays obtained 8 years before. Bone mineral density (evaluated by DEXA) was markedly reduced at the spine and moderately diminished at the proximal femur and total skeleton. Treatment for 11 months with pamidronate (and the addition of hydrochlorotiazide for the last 6 months) reduced to normal values the serum levels of alkaline phosphatase and fasting urinary calcium. The 24-h urinary excretion of calcium and hydroxyproline were also decreased. The BMD increased in all the skeletal areas with presumably hyperactive bone marrow: spine, head, ribs and pelvis (and total skeleton), but did not change at the extremities and diminished at the femoral neck. Patients with CEP may present osteodystrophy characterized by sclerotic lesions and osteopenia, most likely due to accelerated bone turnover in areas of active bone marrow.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Congenital erythropoietic porphyria: skeletal manifestations and effect of pamidronate treatment. 802 43

Haemophagocytic syndromes (HS) are the clinical manifestation of an increased macrophagic activity with haemophagocytosis. Pathophysiology is related to a deregulation of T-lymphocytes and excessive production of cytokines. The main clinicobiological features are fever, hepatosplenomegaly, adenopathies, skin rash, neurological features, cytopenias, hypertriglyceridaemia, hyperferritinaemia and coagulopathy. Diagnosis is based on examination of the bone marrow which shows benign histiocytes actively phagocytosing haemopoietic cells. Acquired HS are mostly associated with an underlying disease such as immunodeficiency, haematological neoplasias and autoimmune diseases. Infection-associated HS was originally described by Risdall in 1979, in viral disease. Since the initial description HS has also been documented in patients with bacterial, parasitic or fungal infections. Epstein-Barr virus (EBV) is the causative agent in most cases. In EBV-associated HS, which sometimes has a fatal course, unregulated T-cell reaction or uncontrolled B-cell proliferation may release cytokines. Management of HS consists of early diagnosis, careful screening for, and prompt treatment of, infections and detection and therapy of any underlying disease. Prognosis of infection-associated haemophagocytic syndrome (IAHS) is better than that in other types of secondary HS. Management of cytokine imbalance should be useful to improve the outcome and reduce the mortality rate in these cases.
Baillieres Best Pract Res Clin Haematol 2000 Jun
PMID:Haemophagocytic syndrome associated with infections. 1094 19

Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology and pathogenesis. AOSD is a rare condition, usually presenting with high fever accompanied by systemic manifestations. The disease is a heterogeneous pathological entity with a range of etiologies, manifestations and prognosis. There is no single diagnostic test for AOSD; rather, the diagnosis is based upon clinical criteria such as arthralgia, fever, skin rash, lymphadenopathy, and hepatosplenomegaly. Determination of the procalcitonin level and the biological response to empirical corticosteroid therapy generally helps the diagnosis, while immune-serology, as a 'screening' test, will not add meaningful information in most cases. Treatment consists of anti-inflammatory medications. Non-steroid anti-inflammatory drugs have limited efficacy, corticosteroid therapy and disease-modifying antirheumatic drugs are usually required. Novel therapeutic approaches, such as anti-tumor necrosis factor blockade and stem cell transplantation, are promising. In this chapter we present clinical and laboratory parameters of 18 patients diagnosed with AOSD at our institution between 1997 and 2003, and review the literature.
Best Pract Res Clin Rheumatol 2004 Oct
PMID:Adult-onset Still's disease. 1545 25

Gain-of-function mutations in LRP5 have been shown to cause high BMD disorders showing variable expression of some clinical symptoms, including torus palatinus and neurological complications. In an extended family, we were able to add craniosynostosis and developmental delay to the clinical spectrum associated with LRP5 mutations. We report on an extended four-generation family with 13 affected individuals (7 men and 6 women) in which an autosomal dominant type of osteosclerosis segregates. Osteosclerosis was most pronounced in the cranial base and calvarium, starting in early childhood with variable expression and a progressive character. Craniosynostosis at an early age was reported in four affected family members (two males and two females). The patients also presented with dysmorphic features (macrocephaly, brachycephaly, wide and high forehead, hypertelorism, prominent cheekbones, prominent jaw). They have normal height and proportions. Neurological complications like entrapment of cranial nerves resulting in optical nerve atrophy, hearing loss, and facial palsy were reported in two individuals. A mild developmental delay was reported in three affected individuals. None of the patients have torus palatinus, increased rate of fractures, osteomyelitis, hepatosplenomegaly, or pancytopenia. A missense mutation 640G-->A (A214T) in the low-density lipoprotein receptor-related protein 5 (LRP5) gene was found in all affected individuals analyzed, including cases in whom craniosynostosis, a mild developmental delay, and/or macrocephaly is observed. To our knowledge, this is the first report in the literature of patients presenting with autosomal dominant osteosclerosis in whom a variable expression of craniosynostosis, macrocephaly, and mild developmental delay is observed, which is most likely associated with a mutation in the LRP5 gene. These phenotypes can therefore be added to the clinical spectrum of LRP5-associated bone disorders.
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PMID:An autosomal dominant high bone mass phenotype in association with craniosynostosis in an extended family is caused by an LRP5 missense mutation. 1594 Mar 80

Systemic juvenile idiopathic arthritis (sJIA) is a rare, systemic inflammatory disease classified as a subtype of JIA. Besides arthritis, it is characterised by systemic features such as spiking fever, skin rash, hepatosplenomegaly or serositis. It is becoming clear now that abnormalities in the innate immunity (cytokines such as interleukin (IL)-1, IL-6 and IL-18, and neutrophils and monocytes/macrophages rather than lymphocytes) play a major role in the pathogenesis of sJIA, distinguishing it from other JIA subtypes. Another distinctive feature of sJIA is its strong association with macrophage activation syndrome (MAS). Based on this, consensus is emerging that sJIA should be viewed as an autoinflammatory syndrome rather than a classic auto-immune disease. As a consequence of the progression in understanding the underlying mechanisms of sJIA, major changes in the management are evolving. So far, treatment has been based on glucocorticosteroids in combination with disease-modifying drugs such as methotrexate. Recently, remarkable improvement has been observed with IL-1 and IL-6 targeted therapies. These therapies might also change the long-term outcome of this disease. However, controlled trials set up in international collaboration are needed to determine the optimal treatment strategies for all sJIA patients.
Best Pract Res Clin Rheumatol 2009 Oct
PMID:Systemic JIA: new developments in the understanding of the pathophysiology and therapy. 1985 30

In adults, elevated transaminases and hepatomegaly, often mild, with moderate to massive idiopathic splenomegaly might hint to a lysosomal storage disease (LSD). In most of these cases, hepatosplenomegaly does not eventually lead to cirrhosis, hepatocellular carcinoma or cholestasis. Nevertheless, the hepatic clinical findings might be the incentive for the patient to present at the physician's office. Many of the currently known >50 lysosomal storage diseases might manifest in liver: out of these, the most important ones in adults are: Gaucher disease, cholesterol ester storage disease (CESD) and the Niemann-Pick diseases. An increase of plasma chitotriosidase should alert the physician for the presence of an LSD. For Gaucher's disease, enzyme supplementation and substrate deprivation constitute effective therapeutic options. Fabry's disease, the most prevalent lysosomal storage disease, does usually not affect the liver, but causes painful episodes of hands' or feet pain (acroparesthesias), left ventricular hypertrophy, renal failure, early stroke and decreased life expectancy. The emerging advent of effective therapeutic options and the cumulative prevalence of lysosomal storage diseases urge the hepatologist to add these diagnostic pathways to the clinical repertoire.
Best Pract Res Clin Gastroenterol 2010 Oct
PMID:Lysosomal storage diseases as differential diagnosis of hepatosplenomegaly. 2095 64

Gaucher disease (GD) is an inherited lysosomal storage disorder affecting multiple organs. Non-neuronopathic GD, the most common form, can present with hepatosplenomegaly, anaemia, bleeding tendencies, thrombocytopenia, skeletal pathologies, growth retardation and, in severe cases, with pulmonary disease. The bone manifestations include bone infarcts, avascular bone necrosis, lytic lesions, osteosclerosis, fractures due to osteoporosis and, rarely, acute osteomyelitis. Bone pain of varying intensity, fractures and joint collapses increase the patients' morbidity and impair their mobility and quality of life. Currently available therapies - enzyme replacement therapy and substrate reduction therapy - have shown to improve blood count and the visceral manifestations within a short time. Beneficial effects have also been documented on bone pain, bone crises and the extent of osteoporosis. The article focusses on the bone pathologies of GD including its pathophysiology, current diagnostics, clinical management and therapeutic effects of enzyme replacement therapy, substrate reduction therapy and bone-specific therapies.
Best Pract Res Clin Rheumatol 2011 Oct
PMID:Miscellaneous non-inflammatory musculoskeletal conditions. Gaucher disease and bone. 2214 46

Myelofibrosis (MF) is a clonal stem cell disorder characterized by ineffective erythropoiesis and extramedullary hematopoiesis leading to progressive bone marrow failure, severe anemia, constitutional symptoms, hepatosplenomegaly, and thrombosis. MF can arise following a history of polycythemia vera (PV) or essential thrombocythemia (ET), or can present de novo as primary myelofibrosis (PMF). The disease course is variable with median survival ranging from months to years. Clinical and biological features such as advanced age, leukocytosis, anemia, transfusion dependence, and elevated inflammatory markers can impact prognosis in patients with PMF. Cytogenetic abnormalities and molecular markers such as JAK2 V617F, ASXL1, and CALR mutations have also been identified as prognostic variables. Several different scoring systems have been developed based on these prognostic factors. In this review, we will discuss the clinical, biological, molecular, and cytogenetic prognostic factors that have been identified in PMF, and the current prognostic models that have been developed to guide treatment decisions.
Best Pract Res Clin Haematol 2014 Jun
PMID:Prognostication in MF: from CBC to cytogenetics to molecular markers. 2518 26

Distinctive facial features, hepatosplenomegaly or cardiomyopathy with or without associated skeletal dysplasia are clinical manifestations that may be suggestive of an underlying lysosomal storage disorder (LSD), However, these features may not be evident in certain subtypes associated primarily with central nervous system involvement. Age at onset can be broad, ranging from infancy to adulthood. Diagnosis may be delayed, as manifestations may be slow to evolve (taking months to years), particularly in those with later (adult-)onset, and in isolated cases (i.e., those without a prior family history). Diagnosis of individual subtypes can be confirmed using a combination of biochemical and molecular assays. In a few LSDs, treatment with hematopoietic stem cell transplantation, enzyme replacement or substrate reduction therapy is available. Symptomatic and palliative measure may enhance quality of life for both treatable and currently untreatable cases. Genetic counseling is important, so patients and their families can be informed of reproductive risks, disease prognosis and therapeutic options. Investigations of underlying disease mechanisms are enhancing knowledge about rare diseases, but also other more common medical conditions, on account of potential convergent disease pathways.
Best Pract Res Clin Endocrinol Metab 2015 Mar
PMID:Non-neuronopathic lysosomal storage disorders: Disease spectrum and treatments. 2598 71

Two distinct metabolic abnormalities are encompassed under the eponym Niemann-Pick disease (NPD). The first is due to the deficient activity of the enzyme acid sphingomyelinase (ASM). Patients with ASM deficiency are classified as having types A and B Niemann-Pick disease (NPD). Type A NPD patients exhibit hepatosplenomegaly in infancy and profound central nervous system involvement. They rarely survive beyond two years of age. Type B patients also have hepatosplenomegaly and pathologic alterations of their lungs, but there are usually no central nervous system signs. The age of onset and rate of disease progression varies greatly among type B patients, and they frequently live into adulthood. Recently, patients with phenotypes intermediate between types A and B NPD also have been identified. These individuals represent the expected continuum caused by inheriting different mutations in the ASM gene (SMPD1). Patients in the second NPD category are designated as having types C and D NPD. These patients may have mild hepatosplenomegaly, but the central nervous system is profoundly affected. Impaired intracellular trafficking of cholesterol causes types C and D NPD, and two distinct gene defects have been found. In this chapter only types A and B NPD will be discussed.
Best Pract Res Clin Endocrinol Metab 2015 Mar
PMID:Types A and B Niemann-Pick disease. 2598 76


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