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

Cholestasis is a common feature of several malignant diseases, including pancreatic, hepatic, gallbladder, and ampullary carcinomas. It is usually secondary to main bile duct obstruction or widespread hepatic metastasis, but it can also be a paraneoplastic syndrome of other underlying malignancies. Stauffer's syndrome is a rare paraneoplastic manifestation of renal cell carcinoma (RCC) that is characterized by elevated alkaline phosphatase, erythrocyte sedimentation rate, alpha-2-globulin, and gamma-glutamyl transferase, thrombocytosis, prolongation of prothrombin time, and hepatosplenomegaly, in the absence of hepatic metastasis and jaundice. A rare variant of this syndrome with jaundice has recently been described in 3 cases in the literature. We report a patient who presented with abdominal pain and cholestatic jaundice in whom RCC was incidentally found during initial workup. Jaundice and liver dysfunction resolved completely after surgical resection of the tumor. This case illustrates the protean manifestations of RCC, and the importance of considering Stauffer's syndrome and its variant in the differential diagnosis of anicteric and icteric cholestasis, which may allow early recognition and treatment of an underlying malignancy.
 ...
PMID:Stauffer's syndrome variant with cholestatic jaundice: a case report. 1680 61

Significant hyperbilirubinaemia, anemia, and splenomegaly are common features in patients with severe haemolysis due to pyruvate kinase (PK) deficiency. Until now, severe neonatal PK deficiency has not been associated with fatal liver disease at this age. We present two neonatal cases of severe PK deficiency complicated with progressive fatal liver disease. The patients presented with severe haemolysis, progressive cholestasis, and hepatosplenomegaly, and both patients ultimately developed liver failure at a very young age. Despite extensive investigations, no specific explanation for liver disease and failure was found. We suggest that the PK deficiency itself directly led to liver dysfunction.
 ...
PMID:Pyruvate kinase deficiency associated with severe liver dysfunction in the newborn. 1765 6

ABCB4 (MDR3), a lipid translocator, moves phosphatidylcholine from the inner to the outer leaflet of the canalicular membrane. Genetic mutations of ABCB4 lead to three distinct but related hepatobiliary diseases. Progressive familial intrahepatic cholestasis (PFIC) type 3 is a chronic cholestatic syndrome characterized by a markedly elevated gamma-glutamyltranspeptidase. Patients present with jaundice, pruritus, and hepatosplenomegaly. Periportal inflammation progresses to biliary cirrhosis and causes portal hypertension. Ursodeoxycholic acid (UDCA) normalizes liver function tests in approximately one half of treated PFIC type 3 patients. Partial responders or nonresponders eventually will require liver transplantation. Gallstone patients with ABCB4 mutations may have low phospholipid-associated cholelithiasis syndrome, characterized by cholesterol gallstones and intrahepatic microlithiasis, along with recurrent biliary symptoms, despite cholecystectomy. Patients with ABCB4 mutations also may develop intrahepatic brown pigment stones. UDCA may improve biliary symptoms even before the dissolution of stones occurs. Additional therapies such as farnesoid X receptor ligands/agonists and benzfibrates show future therapeutic promise. Intrahepatic cholestasis of pregnancy affects pregnant women with abnormal ABCB4. These women suffer from disabling pruritus and also may experience steatorrhea. Fetuses are at high risk for prematurity and stillbirths. The definitive treatment is delivery of the baby. In the interim, limited fat intake, fat-soluble vitamin supplementation, and UDCA with or without S-adenosylmethionine can provide symptomatic relief. Additional hepatobiliary diseases related to ABCB4 mutations are likely to be identified. This may result in the discovery of additional therapies for PFIC type 3, gallstones, and intrahepatic cholestasis of pregnancy.
 ...
PMID:The Multiple Facets of ABCB4 (MDR3) Deficiency. 1822 10

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.
 ...
PMID:Lysosomal storage diseases as differential diagnosis of hepatosplenomegaly. 2095 64

Hyperargininemia is a rare inborn error of metabolism due to arginase deficiency, which is inherited in an autossomal recessive manner. Arginase is the final enzyme of the urea cycle and catalyzes the conversion of arginine to urea and ornithine. This condition typically presents in early childhood (between 2 and 4 years of age) with developmental delay associated with progressive spastic paraparesis. Neonatal presentation is very uncommon with a poorly described outcome. Here, we discuss two cases of neonatal cholestasis as initial clinical presentation of hyperargininemia. In case 1, diagnosis was established at 2 months of age upon investigation of the etiology of cholestatic injury pattern and hepatosplenomegaly, and treatment was then initiated at when the patient was 3 months old. Unfortunately, the patient had progressive biliary cirrhosis to end-stage liver disease complicated with portal hypertension for which she underwent successful orthotopic liver transplant at 7 years of age. In case 2, hyperargininemia was identified through newborn screening and treatment was started when patient was 21 days old. Cholestasis was only identified in the patient's further evaluation and it resolved 2 weeks into treatment. The patient is currently 18 months old and her development and neurological examination remain unremarkable. Neonatal cholestasis as first presentation of hyperargininemia is rare, but this disorder should be included in the differential diagnosis of unexplained cholestasis in the neonate. In fact, these two cases suggest that arginase deficiency may be the cause of cholestatic liver disease.
 ...
PMID:Neonatal cholestasis: an uncommon presentation of hyperargininemia. 2122 17

Mitochondrial disorders recognized in the neonatal period usually present as a metabolic crisis combined with one or several organ manifestations. Liver disorder in association with a respiratory chain deficiency may be overlooked since liver dysfunction is common in severely sick newborn infants. Lactacidosis, hypoglycemia, elevated serum transaminases and conjugated bilirubin are common signs of mitochondrial hepatopathy. Hepatosplenomegaly may occur in severe cases. A clinical picture with fetal growth restriction, postnatal lactacidosis, hypoglycemia, coagulopathy, and cholestasis, especially in combination with neurological symptoms or renal tubulopathy, should alert the neonatologist to direct investigations on mitochondrial disorder. A normal lactate level does not exclude respiratory chain defects. The most common liver manifestation caused by mutated mitochondrial DNA (deletion) is Pearson syndrome. Recently, mutations in several nuclear DNA genes have been identified that lead to mitochondrial hepatopathy, e.g. mitochondrial depletion syndrome caused by DGUOK, MPV17, SUCLG1, POLG1, or C10ORF2 mutations. A combination of lactacidosis, liver involvement, and Fanconi type renal tubulopathy is common when the complex III assembly factor BCS1L harbors mutations, the most severe disease with consistent genotype-phenotype correlation being the GRACILE syndrome. Mutations in nuclear translation factor genes (TRMU, EFG1, and EFTu) of the respiratory chain enzyme complexes have recently been identified. Diagnostic work-up of neonatal liver disorder should include assessment of function and structure of the complexes as well as mutation screening for known genes. So far, treatment is mainly symptomatic.
 ...
PMID:Mitochondrial hepatopathies in the newborn period. 2168 Feb 70

Citrin deficiency (CD) is an autosomal recessive disorder with SLC25A13 as causative gene that encodes citrin, the liver-type aspartate/glutamate carrier isoform 2 (AGC2). Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), the major CD phenotype at pediatric age, has been previously reported as a self-limiting condition with clinical presentations resolving between 6 months and 1 year of life. We report the prenatal diagnosis of CD in a family with a fatal NICCD proband. The proband was a 10-month-old male presenting cough for 8 days and jaundiced skin 1 day. Physical examination revealed fever, dark jaundiced sclera and skin, hoarse breathing sounds, and hepatosplenomegaly. Laboratory tests uncovered elevated cholestatic indices, increased ammonia, and prolonged activated partial thromboplastin time and prothrombin time, and reduced fibrinogen. Sonography showed the features of liver cirrhosis. Metabolome analysis uncovered large quantity of 4-hydroxyphenyllactate and dicarboxylates in urine and increased citrulline and methionine in blood. The patient passed away due to liver failure at his age of 13.5 months. Mutation analysis revealed him a homozygote of 851del4, a four-base deletion in exon 9 of SLC25A13 gene. On request of the parents who had a second fetus, prenatal diagnosis of CD was performed by PCR-electrophoresis following amniocentesis and amniocyte culture, and demonstrated the fetus a carrier of the same mutation. The fatal proband in the present report has provided clinical evidence challenging the traditional concept on NICCD prognosis. Moreover, as the first trial on CD prenatal diagnosis, this study might open a novel area for clinical management of CD.
 ...
PMID:Prenatal diagnosis of citrin deficiency in a Chinese family with a fatal proband. 2209 53

Niemann-Pick type C (NPC; OMIM 257219) disease is a neurodegenerative lysosomal storage disorder characterized by accumulation of unesterified cholesterol in the lysosomal/late endosomal system. This autosomal recessive disorder occurs in approximately 1/150,000 births. The broad clinical spectrum ranges from a prenatal severe presentation to an adult-onset chronic neurodegenerative disease. Data about prenatal presentation of NPC are limited. A female newborn was born at 34(2) weeks' gestation with a birth weight of 3070 g, and transferred to the Neonatal Intensive Care Unit because of nonimmune hydrops fetalis (NIHF) and respiratory distress. On admission, a physical examination revealed skin edema, mild respiratory distress, and abdominal distention due to massive ascites. Hepatosplenomegaly and cholestasis increased progressively and bleeding diathesis occurred. Results of an abdominal ultrasonography showed hepatosplenomegaly and segmental multicystic dysplastic left kidney. Foamy cells with a lysosomal phospholipid storage pattern compatible with NPC were found in the bone marrow smear. Cultured fibroblasts showed a strongly elevated filipin staining (classical NPC cellular phenotype), establishing the diagnosis of NPC. The infant died on the 52(nd) day of life because of respiratory distress due to lung involvement of NPC, massive ascites, and progressive liver failure. Results of an autopsy showed multiorgan storage disease involving the liver, spleen, lymph nodes, thymus, lungs, and brain. Here, we present a preterm infant with NIHF as a sign of severe prenatal-onset NPC and review the literature.
 ...
PMID:Prenatal-onset Niemann-Pick type C disease with nonimmune hydrops fetalis. 2412 Jan 57

Leukemoid reaction, defined as a total leukocyte count of >50,000/mm, is most commonly related to antenatal administration of steroids, infections, and transient myeloproliferative disorder of Down syndrome in newborns. Atypical presentations of viral infections can be a diagnostic challenge in the newborn period. Cytomegalovirus (CMV) infection causes a multisystem disease, and symptomatic infants generally present with intrauterine growth restriction, hepatosplenomegaly, cholestasis, rash, thrombocytopenia, and microcephaly. We present a case of a preterm infant with severe myeloid leukemoid reaction (leukocyte count >100,000/mm) at birth who was diagnosed with congenital CMV infection on the basis of CMV polymerase chain reaction results after the appearance of cholestasis, blueberry muffin rash, and hepatosplenomegaly.
...
PMID:Severe leukemoid reaction in a preterm infant with congenital cytomegalovirus infection. 2407 52

Congenital erythropoietic porphyria is a rare autosomal recessive disorder of porphyrin metabolism in which the genetic defect is the deficiency of uroporphyrinogen III cosynthase (UIIIC). Deficiency of this enzyme results in an accumulation of high amounts of uroporphyrin I in all tissues, leading to hemolytic anemia, splenomegaly, erythrodontia, bone fragility, exquisite photosensitivity, and mutilating skin lesions. We discuss a female infantile case who was admitted for jaundice; bullous lesions appeared on her trunk during phototherapy in the neonatal period. The skin biopsy findings were consistent with epidermolysis bullosa. Due to persistent hepatosplenomegaly and cholestasis, metabolic tests and liver biopsy were performed. During the follow-up, hemolytic anemia and red urine were detected. The levels of porphyrin metabolites were determined at high concentrations in plasma, stool and urine analysis, which were suggestive of congenital erythropoietic porphyria.
...
PMID:Bullous skin lesions in a jaundiced infant after phototherapy: a case of congenital erythropoietic porphyria. 2419 86


<< Previous 1 2 3 4 5 6 Next >>