Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary hemochromatosis (HH) is the most common autosomal recessive disorder in populations of caucasian origin with a prevalence of 1 : 200-400 for homozygous patients. Currently, 4 types of HH are distinguished. The classical and most common form is type 1 hemochromatosis which is characterized by HFE gene mutations on chromosome 6. The disease results from an excessive iron absorption leading to multiple manifestations such as hepatomegaly, diabetes mellitus, cardiomyopathy, infertility, and hepatic fibrosis/cirrhosis if untreated. A distinct clinical feature of hemochromatosis is represented by involvement of the joints (arthropathy of hemochromatosis) which occurs frequently and often before iron overload is present. Severity of arthropathy usually does not correlate with the extent of iron overload. In contrast to most other manifestations, it is not improved by iron depletion but can be treated symptomatically. This review outlines clinical aspects as well as pathogenesis, diagnosis and therapy of the disease.
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PMID:[Arthropathy of hereditary hemochromatosis]. 1499 Dec 75

Mulibrey nanism is an autosomal recessive prenatal-onset growth disorder characterized by dysmorphic features, cardiomyopathy, and hepatomegaly. Mutations in TRIM37 encoding a tripartite motif (TRIM, RING-B-box-coiled-coil)-family protein underlie mulibrey nanism. We investigated the ubiquitin ligase activity predicted for the RING domain of TRIM37 by analyzing its autoubiquitination. Full-length TRIM37 and its TRIM domain were highly polyubiquitinated when co-expressed with ubiquitin. Polyubiquitination was decreased in a mutant protein with disrupted RING domain (Cys35Ser;Cys36Ser) and in the Leu76Pro mutant protein, a disease-associated missense mutation affecting the TRIM domain of TRIM37. Bacterially produced GST-TRIM domain fusion protein, but not its Cys35Ser;Cys36Ser or Leu76Pro mutants, were polyubiquitinated in cell-free conditions, implying RING-dependent modification. Ubiquitin was also identified as an interaction partner for TRIM37 in a yeast two-hybrid screen. Ectopically expressed TRIM37 rapidly formed aggregates that were ubiquitin-, proteasome subunit-, and chaperone-positive in immunofluorescence analysis, defining them as aggresomes. The Cys35Ser;Cys36Ser mutant and the Leu76Pro and Gly322Val patient mutant proteins were markedly less prone to aggregation, implying that aggresomal targeting reflects a physiological function of TRIM37. These findings suggest that TRIM37 acts as a TRIM domain-dependent E3 ubiquitin ligase and imply defective ubiquitin-dependent degradation of an as-yet-unidentified target protein in the pathogenesis of mulibrey nanism.
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PMID:TRIM37 defective in mulibrey nanism is a novel RING finger ubiquitin E3 ligase. 1588 86

Amyloidosis is an uncommon plasma-cell dyscrasia with an incidence of eight patients per million per year. It is often difficult to recognize because of the myriad symptoms and vague nature of the clinical presentation. Symptoms include fatigue, dyspnea, edema, paresthesias, and weight loss. Clinical syndromes at presentation include nephrotic-range proteinuria with or without renal insufficiency, cardiomyopathy, hepatomegaly, symptomatic peripheral neuropathy, and autonomic failure. Recent advances have occurred in evaluation of patients by using the free light chain assay and new prognostic assessments with cardiac biomarkers. Newly developed therapeutic strategies, involving high-dose and intermediate-dose chemotherapy, have evolved in the last 3 years. This paper reviews a diagnostic pathway clinicians can use to diagnose the disorder, assess a patient's prognosis, and logically plan a therapeutic strategy.
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PMID:Amyloidosis. 1602 46

Amyloidosis is a rare plasma cell proliferative disorder. The annual incidence in Olmsted County, Minnesota, is 8 in 1,000,000 patients. This is a difficult disorder to diagnose, because the symptoms at presentation are vague and include dyspnea, paresthesias, edema, weight loss, and fatigue. The clinical syndromes at the time of presentation include nephrotic-range proteinuria with or without renal failure, cardiomyopathy, "atypical multiple myeloma," hepatomegaly, and autonomic or peripheral neuropathy. The serum immunoglobulin free light chain assay has been an important step forward in classifying systemic amyloidosis as an immunoglobulin light chain form and in monitoring therapy. Recently, the importance of serum cardiac biomarkers in assessing outcome has been recognized. New therapies developed over the past 5 years include high-dose chemotherapy with stem cell reconstitution, combinations of alkylating agents with dexamethasone, and, most recently, thalidomide.
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PMID:Amyloidosis: diagnosis and management. 1635 26

Glycogenosis type III (Cori disease) is an autosomal recessive disorder caused by the deficiency of the glycogen debranching enzyme, encoded by the AGL gene, and existing in six isoforms alternately spliced in a tissue-specific way. Generally, disease onset occurs early on starting from the first year of life, with hepatomegaly, hypoglycemia, hyperlipidemia, increased CK levels, and, in some cases, short stature and slight mental retardation. Frequently, hepatomegaly tends to resolve spontaneously and inexplicably during childhood, when myopathy, often associated with cardiomyopathy, arises. This disease is known to lack almost invariably clear links between the genotype and clinical phenotype. We describe nine new mutations in Italian patients: four nonsense (p.Arg285X, p.Lys422X, p.Arg910X, p.Arg977X), three frameshift (c.442delA, c.753_756delGACA, c.3963delG), and two missense (p.Ala1120Pro, p.Arg524His). Particularly, the nonsense p.Arg285X is linked to an exonic splicing enhancer and it was found to produce two species of transcripts at the same time. Moreover, we discuss a subgroup of subjects carrying c.2681+1G>A, which has proven to be the most frequent mutation among our patients. The previously described c.664+3A>G was also detected in two patients, both homozygous. The present work is yet another confirmation that the individual genetic background plays a pivotal role in influencing the phenotypes, as occurs in other metabolic diseases.
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PMID:Hepatic and neuromuscular forms of glycogenosis type III: nine mutations in AGL. 1670 13

Primary systemic amyloidosis is a rare disease with protean manifestations. Presence of nephrotic syndrome in the absence of diabetes and hypertension, cardiomyopathy in the absence of ischemia, restrictive cardiac defect, demyelinating polyneuropathy, or unexplained hepatomegaly should alert the physician to the possibility of amyloidosis. Initial steps in the diagnostic evaluation of patients with suspected amyloidosis include serum and urine immunoelectrophoresis and immunofixation studies. Demonstration of amyloid material on tissue biopsy (e.g., subcutaneous fat) is required for diagnosis. Availability of effective treatments has improved the outlook of patients with primary systemic amyloidosis. Early diagnosis is critical to optimizing the chances of effective therapy.
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PMID:Primary systemic amyloidosis. Early diagnosis and therapy can improve survival rates and quality of life. 1691 52

Patients with long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) deficiency manifest hypoketotic hypoglycemia, hepatomegaly, hypotonia, lactic acidemia, acute renal failure, cardiomyopathy, and sudden death. We describe four novel mutations of the alpha- and beta-subunits of the mitochondrial trifunctional protein in four patients from three unrelated families. Their plasma acylcarnitine profiles suggested the presence of LCHAD deficiency by demonstrating highly elevated 3-hydroxyacyl carnitines by tandem mass spectrometry (MS/MS). Patients 1 and 2 had siblings who had died of lactic acidemia during the neonatal period. These patients also manifested lactic acidemia and died in the neonatal period. Patient 3 had a family history of Reye-like syndrome. She exhibited acute renal failure, rhabdomyolysis, pericardial effusion, and myopathy at the age of 12 years. DNA analysis of patients 1 and 2 revealed homozygosity for a c.1689+2T>G mutation of the HADHA gene, resulting in the skipping of exon 16 with an in-frame 69-bp deletion. Patient 3 was a compound heterozygosity of the HADHB gene, N307D/N389D. Patient 4, a 25-month-old baby, manifested recurrent episodes of lethargy, metabolic acidosis, elevated liver enzymes, and dark urine from the age of 10 months. Mutation analysis of the HADHB gene of patient 4 identified compound heterozygosity of N114D/N307D.
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PMID:Identification of novel mutations of the HADHA and HADHB genes in patients with mitochondrial trifunctional protein deficiency. 1714 51

alpha-N-Acetylgalactosaminidase deficiency is a lysosomal disorder with clinically very different infantile and adult forms. To date, 12 patients from eight families are known. Neuroaxonal dystrophy or moderate psychomotor retardation, without visceral involvement, have been reported in the infantile form. We describe a new Spanish patient with Schindler disease who presented with hepatomegaly and cardiomyopathy, traits not previously associated with this disease. There was no dysmorphism or neurological involvement in the patient, who died at the age of 8 months. alpha-N-Acetylgalactosaminidase activity was reduced in fibroblasts and liver to 1.6% and 0.57% of controls, respectively. Several lysosomal enzyme activities associated with infantile cardiomyopathy were found in the normal ranges. The patient was a compound heterozygote for the novel mutation p.D217N (c.649G>A) in exon 6 and the already reported mutation p.E325K (c.973G>A) in exon 8. The description of this new case broadens the clinical spectrum of the infantile forms and indicates that Schindler disease should be considered in the diagnosis of metabolic cardiomyopathies.
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PMID:A new infantile case of alpha-N-acetylgalactosaminidase deficiency. Cardiomyopathy as a presenting symptom. 1717 32

Here we report a newborn with VLCAD deficiency with a severe neonatal onset type who presented with hypoglycemia, cardiomyopathy, mild hepatomegaly and slight hypoalbuminemia. The patient was also homozygous for a new missense mutation (R456H). Postmortem examination of the liver, heart and skeletal muscle revealed diffuse lipid accumulation in various amounts. Mild lobular and portal fibrosis as well as severe macrovesicular steatosis were also found in the liver. The fatal course of the patient may have resulted from diffuse lipid accumulation in the liver and myocardium, which probably began during the intrauterine life with slight hypoalbuminemia as a silent marker of this process.
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PMID:A newborn with VLCAD deficiency. Clinical, biochemical, and histopathological findings. 1720 56

Primary (AL) amyloidosis is the most common form of systemic amyloidosis seen in current clinical practice. The symptoms of the disease are usually vague, special features are seen in fewer than one fifth of patients, and the combination of organs and systems involved provides a clue for the diagnosis. We describe a patient in whom asymptomatic hepatomegaly, cardiomegaly, hyperlipidaemia and elevated serum alkaline phosphatase level were found during routine examination; the final diagnosis was primary systemic AL amyloidosis with severe cardiomyopathy, resulting in a fatal outcome within eight months from the diagnosis.
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PMID:Unusual initial presentation of primary systemic (AL) amyloidosis with severe cardiomyopathy and fatal outcome. 1724 12


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