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)

Glycogen storage disease type IX (GSD type IX) results from a deficiency of hepatic phosphorylase kinase activity. The phosphorylase kinase holoenzyme is made up of four copies of each of four subunits (alpha, beta, gamma and delta). The liver isoforms of the alpha-, beta- and gamma-subunits are encoded by PHKA2, PHKB and PHKG2, respectively. Mutation within these genes has been shown to result in GSD type IX. The diagnosis of GSD type IX is complicated by the spectrum of clinical symptoms, variation in tissue specificity and severity, and its inheritance, either X-linked or autosomal recessive. We investigated 15 patients from 12 families with suspected GSD type IX. Accurate diagnosis had been hampered by enzymology not being diagnostic in five cases. Clinical symptoms included combinations of hypoglycaemia, hepatosplenomegaly, short stature, hepatopathy, weakness, fatigue and motor delay. Biochemical findings included elevated lactate, urate and lipids. We characterised causative mutations in the PHKA2 gene in ten patients from eight families, in PHKG2 in two unrelated patients and in the PHKB gene in three patients from two families. Seven novel mutations were identified in PHKA2 (p.I337X, p.P498L, p.P869R, p.Y116_T120dup, p.R1070del, p.R916W and p.M113I), two in PHKG2 (p.L144P and p.H48QfsX5) and two in PHKB (p.Y419X and c.2336+965A>C). There was a severe phenotype in patients with PHKG2 mutations, a mild phenotype with patients PHKB mutations and a broad spectrum associated with PHKA2 mutations. Molecular analysis allows accurate diagnosis where enzymology is uninformative and identifies the pattern of inheritance permitting counselling and family studies.
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PMID:Glycogen storage disease type IX: High variability in clinical phenotype. 1768 25

We report the case of a 22-year-old woman who presented with acute onset flaccid quadriparesis. Physical examination showed mild pallor with cervical and axillary lymphadenopathy, hepatomegaly, and bilateral smooth enlarged kidneys. Neurological examination revealed lower motor neuron muscle weakness in all the four limbs with hyporeflexia and normal sensory examination. Laboratory investigations showed anemia, severe hypokalemia, and metabolic acidosis. Urinalysis showed a specific gravity of 1.010, pH of 7.0, with a positive urine anion gap. Ultrasound revealed hepatosplenomegaly with bilateral enlarged smooth kidneys. Renal biopsy was consistent with the diagnosis of non-Hodgkin lymphoma (B cell type). Metabolic acidosis, alkaline urine, and severe hypokalemia due to excessive urinary loss in our patient were suggestive of distal renal tubular acidosis. Renal involvement in lymphoma is usually subclinical and clinically overt renal disease is rare. Diffuse lymphomatous infiltration of the kidneys may cause tubular dysfunction and present with hypokalemic paralysis.
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PMID:Diffuse lymphomatous infiltration of kidney presenting as renal tubular acidosis and hypokalemic paralysis: case report. 1807 21

Gaucher disease is a recessively inherited lysosomal storage disorder, caused by deficiency of glucocerebrosidase activity. Affected individuals usually present with hepatosplenomegaly, anaemia, thrombocytopenia, and skeletal diseases. A wide range of neurological manifestations have also been recognized in Gaucher patients including acute neurological deterioration in infancy, mental retardation, ocular motor apraxia, seizure, and parkinsonism. Although muscle weakness is not an uncommon finding in patients with Gaucher disease, the aetiology of weakness is not well understood. We prospectively investigated seven Gaucher patients and found that four of them (patients 1-4) had mild to moderate degree of proximal-predominant symmetrical muscle weakness in four limbs. By history, three patients (patients 1-3) developed insidious onset of nonprogressive muscle weakness in four limbs with easy muscle fatigue from adolescence. A needle electromyographic study detected some small, brief polyphasic waves in these four patients. Muscle biopsy in one patient (patient 1) showed a few atrophic type II muscle fibres without infiltration of Gaucher cells. Three patients (patients 1-3) continuously received enzyme replacement therapy with imiglucerase and their muscle strength seemed improved after two years. We concluded that Gaucher disease may be associated with myopathy.
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PMID:Myopathy in Gaucher disease. 1819 73

Pyogenic liver abscess (PLA) is a process with significant morbidity and mortality and is a rare complication in an aisled way in patients with autosomal dominant polycystic kidney disease (ADPKD). In addition to hepatic cyst infection, intracystic hemorrhage is another complication seen in ADPKD patients; however, the liver parenchyma itself remains normal. A PLA located in normal liver tissue in these kinds of patients has not been previously reported. Fusobacterium nucleatum is an anaerobic bacterium with rare involvement other than in periodontal infections. A 58-year-old Caucasian male, who was on hemodialysis treatment from July 2004 due to end-stage renal disease secondary to ADPKD, was admitted with fever, rigor, chills, weakness, and abdominal pain of 10 days duration. During that time, ciprofloxacin 500 mg, twice daily, gentamycin 80 mg/48 h, and vancomycin 1 g/week, were prescribed, but treatment was interrupted by hospitalization. Physical examination on admission revealed that the patient had a fever of 39.8 degrees C, pallor, chills, right upper quadrant abdominal pain, and hepatosplenomegaly. Abdominal ultrasound revealed a 5.3 cm diameter collection with irregular configuration located in the caudate lobe. Abdominal computed tomography (CT) showed a large multiloculated hepatic collection. The PLA was managed with antibiotics (metronidazole) and continuous catheter drainage (8Fr drainage catheters [Abocath-T, Abbott, Sligo, Ireland]) into the abscess. Fluid culture was positive for F. nucleatum. Complete remission was obtained after 12 days without complications. We describe a PLA by F. nucleatum, in a very rare location in an ADPKD patient undergoing hemodialysis without complicated cysts, managed with antibiotics and percutaneous drainage with satisfactory resolution.
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PMID:A case report of a pyogenic liver abscess caused by Fusobacterium nucleatum in a patient with autosomal dominant polycystic kidney disease undergoing hemodialysis. 1825 20

Hematological complications have been frequently associated with acute brucellosis, but pancytopenia is less frequently seen. Also, capillary leak syndrome has been rarely reported in the literature. In this report, we present a case of brucellosis with pancytopenia leading to capillary leak syndrome. A 21-year-old man was admitted to hospital with complaints of a one-month history of weakness, sweats, and fever and he had hepatosplenomegaly and edema over the pretibial areas. Hemogram revealed pancytopenia and biochemical tests revealed moderate hypoalbuminemia, elevations of lactate dehydrogenase and aspartate aminotransferase. He was diagnosed as brucellosis and capillary leak syndrome. He was given doxycycline and rifampicin. The patient's symptoms were resolved after treatment.
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PMID:The first documented case of brucellosis manifested with pancytopenia and capillary leak syndrome. 1845 81

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by extreme paucity of adipose tissue from birth, and early onset of metabolic complications related to insulin resistance. Mutations in three genes, 1-acylglycerol 3-phosphate-O-acyltransferase 2 (AGPAT2), Berardinelli Seip Congenital Lipodystrophy 2 (BSCL2), and Caveolin-1 (CAV1) are associated with the three subtypes of this disorder, CGL1, CGL2 and CGL3, respectively. We report two siblings of Hispanic origin who displayed characteristic features of CGL such as generalized loss of subcutaneous fat from birth, acanthosis nigricans, acromegaloid habitus, umbilical prominence, hepatosplenomegaly, hypoleptinemia, dyslipidemia, and insulin resistance. However, no disease causing variants were detected in the DNA sequence of AGPAT2, BSCL2 or CAV1 genes. Further, whole body magnetic resonance imaging (MRI) in the two siblings revealed marked loss of subcutaneous, intraabdominal and intrathoracic fat like in other patients with CGL, but preservation of bone marrow fat which is invariably lost in all patients with CGL1 and CGL2, but not in the patient reported with CGL3. They also had generalized muscle weakness during infancy and early childhood associated with a nearly fivefold increase in serum creatine kinase (CK) levels, but with normal muscle biopsy and electrophysiologic studies. Both patients were also found to have atlantoaxial dislocation requiring surgical intervention. Thus, this pedigree represents a novel subtype of CGL characterized by generalized loss of body fat but with preservation of bone marrow fat, congenital muscular weakness and cervical spine instability. The genetic basis of this novel subtype remains to be determined.
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PMID:Novel subtype of congenital generalized lipodystrophy associated with muscular weakness and cervical spine instability. 1869 12

We report four sporadic and three familial patients with Camurati-Engelmann disease. One patient had follow-up examinations over 8 years. Pain in the extremities and muscle weakness were common clinical symptoms. Most patients also had cranial nerve impairment, hepatosplenomegaly, a waddling gait, and elevated serum alkaline phosphatase levels. Long bones were affected in all. We discuss the differential diagnosis for this interesting bone entity.
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PMID:Camurati-Engelmann disease: imaging, clinical features and differential diagnosis. 1921 2

A 24-year-old man was referred to our clinic in August 2003 with complaints of weakness, dizziness, and bilateral knee pain of 3 years' duration. Bilateral digital clubbing had been found on routine physical examination during his military service 4 years earlier. There were no cardiorespiratory or abdominal symptoms. There was no compromise in the activities of everyday life. The patient was not a chronic smoker. In the family history of the patient, his brother had been diagnosed with pachydermoperiostosis in another center 2 years earlier, but did not return to the hospital for a follow-up investigation of myelofibrosis. On physical examination, the patient showed marked drumstick clubbing of the hands (Fig. 1), and a pale general appearance. The causes of digital clubbing are shown in Table 1 (Fawcett RS, Linford S, Stulberg DL. Nail abnormalities: clues to systemic disease. Am Fam Physician 2004; 69: 1417-1424). Deep nasolabial folds were seen on the face. Skin hypertrophy, cutis verticis gyrata, and seborrhea on the face were also observed. The patient also complained of hyperhidrosis. Examination of the cardiovascular system was normal. There was bilateral swelling of the ankle and knee (Fig. 2). Hepatosplenomegaly was found on abdominal examination. Investigations showed hypochromic microcytic anemia [hemoglobin, 8.58 g/dL (normal, 12.2-18.1 g/dL); hematocrit, 28.1% (normal, 37.7-53.7%); white blood cell count, 3430/mm(3) (normal, 4600-10,200/mm(3)); neutrophils, 2470/mm(3) (normal, 2000-6900/mm(3)); lymphocytes, 820/mm(3) (normal, 600-3400/mm(3)); platelets, 162,000/mm(3) (normal, 142,000-424,000 mm(3)); mean corpuscular volume, 73.7 fL (normal, 80-97 fL)]. Anisocytosis, poikilocytosis, microcytosis, and hypochromia were observed on peripheral blood examination, and the erythrocyte sedimentation rate was 37 mm/h. The serum C-reactive protein level was 50.1 mg/L (normal, 0-5 mg/L). Biochemical parameters, including serum calcium, phosphate, alkaline phosphates and liver function tests, were found to be within the normal range. The causes of secondary hypertrophic osteoarthropathy associated with pulmonary, rheumatologic, endocrine, cardiac, and gastroenterologic disorders were excluded. Growth hormone level and thyroid function tests were normal. Antinuclear antibody, TORCH [Toxoplasma immunoglobulin M (IgM), rubella IgM, cytomegalovirus IgM, herpes simplex IgM] panel, and markers of hepatitis were negative. Serum Igs and rheumatoid factor were found to be within the normal range. There was subperiosteal new bone formation on bilateral knee X-ray (Fig. 3). Radiography of the chest, pulmonary function tests, arterial blood gas, and echocardiography were normal. Abdominal ultrasonography revealed hepatosplenomegaly. Amyloid deposition was not determined in rectal biopsy. Reticulin-type myelofibrosis was found on bone marrow biopsy (Figs 4 and 5). In the cytogenetic study, monosomy 22 was detected in four of 20 metaphase plates.
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PMID:An interesting case of pachydermoperiostosis with idiopathic myelofibrosis associated with monosomy 22. 1965 69

We present the case of a 25-year-old woman with a history of weakness, weight loss, anemia, and elevated liver enzymes. Outpatient diagnostic evaluation, including abdominal ultrasound and endoscopies, revealed no conclusive explanation for the clinical picture and the patient was admitted to our clinic. Because of the hepatosplenomegaly together with the elevated liver enzymes, one of our differential diagnoses was that of liver disease. To clarify this, we performed a minilaparoscopy, which showed multiple diffuse distributed spots of livid color without clear margins distributed all over both liver lobes. A biopsy taken from these areas revealed the diagnosis of peliosis hepatis with irregular and diffusely enlarged hepatic sinusoids with an irregular structure. Peliosis hepatis is associated with numerous infectious and neoplastic diseases, but also occurs as a result of toxic liver damage. Further evaluation of our patient with an x-ray and a computed tomography (CT) scan revealed a mediastinal mass and a CT-guided biopsy showed classical Hodgkin's lymphoma. After completing further screening, a definitive diagnosis of Hodgkin's lymphoma stage II/N/B (Ann-Arbor) was established and chemotherapy according to the German Hodgkin's study group protocol with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (the BEACOPP regimen) was initiated. After the first chemotherapy cycle, the patient's symptoms and laboratory values improved rapidly. Taken together, we present the case of a patient with peliosis hepatis as an uncommon manifestation of Hodgkin's lymphoma. Despite an extensive literature search, we could not find any case of peliosis hepatis associated with a de novo diagnosis of classical Hodgkin's disease.
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PMID:First reported case of disease: peliosis hepatis as cardinal symptom of Hodgkin's lymphoma. 1988 16

Histiocytic sarcoma (HS) is a very rare neoplasm that often shows an aggressive clinical course and systemic symptoms, such as fever, weight loss, adenopathy, hepatosplenomegaly and pancytopenia. It may present as localized or disseminated disease. We describe here a 63-yr-old male who manifested systemic symptoms, including fever, weight loss and generalized weakness. Abdominal and chest computed tomography failed to show specific findings, but there was suspicion of multiple bony changes at the lumbar spine. Fusion whole body positron emission tomography, bone scan and lumbar spine magnetic resonance imaging showed multiple bone lesions, suggesting a malignancy involving the bone marrow (BM). Several BM and bone biopsies were inconclusive for diagnosis. Necropsy showed replacement of the BM by a diffuse proliferation of neoplastic cells with markedly increased cellularity (95%). The neoplastic cells were positive for lysozyme and CD68, but negative for T- and B-cell lineage markers, and megakaryocytic, epithelial, muscular and melanocytic markers. Morphologic findings also distinguished it from other dendritic cell neoplasms.
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PMID:A case of histiocytic sarcoma presenting with primary bone marrow involvement. 2011 90


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