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)

A study of 11 autopsied cases of the cerebro-hepato-renal syndrome of Zellweger (ZS) is reported. All cases had severe, persistent congenital hypotonia, hepatic lobular disarray, renal cortical cysts and pulmonary hypoplasia. Many had cardiovascular malformations, hepatomegaly, cerebral cortical gyral maldevelopment and pancreatic islet hyperplasia. Additional, less frequent findings are delineated. Results of iron content studies of hepatic and renal tissues are related to age of survival and possible development of fibrosis.
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PMID:Studies of malformation syndromes of man XIB: the cerebro-hepato-renal syndrome of Zellweger: comparative pathology. 124 88

Peroxisome-deficient disorders including Zellweger syndrome, neonatal adrenoleukodystrophy and infantile Refsum disease are characterized by hypotonia, psychomotor delay, hepatomegaly and dysmorphism. Multiple peroxisomal enzymes are deficient in these disorders probably due to the defect of transport machinery of enzymes. Defects of beta-oxidation enzymes causes an accumulation of very-long-chain fatty acids, which is closely related to the pathogenesis. Catalase, a marker enzyme of peroxisome, is distributed in the cytosol. Immunocytochemical staining of peroxisomes using anti-catalase is a useful tool for prenatal and postnatal diagnosis. Although the primary etiology of peroxisomal deficiency has not been determined, genetic heterogeneity was clarified by complementation studies. At least 8 genes are involved in the formation of functional peroxisomes.
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PMID:[Clinical biochemical and genetic aspects of peroxisome-deficient disorders]. 137 33

The cerebrohepatorenal syndrome of Zellweger is a congenital syndrome of multiple manifestations, including hepatomegaly and liver dysfunction. Treatment is generally of a supportive nature, aimed at improving nutrition and growth, controlling the central nervous system symptoms and limiting progression of liver disease. Because the liver disease in Zellweger syndrome may be attributed to an overproduction and accumulation of cholestanoic acids, exacerbated by diminished primary bile acid synthesis, we hypothesized that primary bile acid administration would be beneficial in improving liver function by a mechanism involving down-regulation in the synthesis of these atypical bile acids. We report here the clinical and biochemical responses to primary bile acid administration in a 2-mo-old boy who was seen with the typical signs of Zellweger syndrome. Liver disease was evident from hepatomegaly and elevated serum liver enzymes and bilirubin. The diagnosis was supported by markedly elevated serum very long chain fatty acids and the bile acids dihydroxycholestanoic acid and trihydroxycholestanoic acid. Confirmation of the lack of peroxisomes was established by electron microscopy. When the patient was 6 mo old, the primary bile acids cholic acid and chenodeoxycholic acid, (100 mg each/day) were administered orally. A significant improvement in biochemical indices of liver function occurred with a normalization of the serum bilirubin and liver enzymes and a histological improvement in the extent of inflammation and bile duct proliferation and disappearance of cannalicular plugs. Serum and urinary cholestanoic acids showed a significant decrease within a few days. A striking and sustained increase in growth was observed after therapy, and an improvement in neurological symptoms was noted. In conclusion, this study indicates that primary bile acid therapy improves liver function and growth in the patient with peroxisomal dysfunction and should be considered in the supportive therapies for this condition.
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PMID:Oral bile acid treatment and the patient with Zellweger syndrome. 173 22

We describe a relatively new syndrome in four children with characteristic facial dysmorphism, sensorineural hearing loss, severe visual impairment with retinitis pigmentosa, hypotonia, hepatomegaly, and severe developmental delay. Two patients had intracranial hemorrhage secondary to a vitamin K-responsive clotting defect; both had steatorrhea. Liver biopsy specimens in two children showed an accentuated lobular architecture with prominent fibrous bands in the portal area. In one, the ultrastructure showed accumulation of abnormal substances and occasional trilaminar structures in hepatocytes and other cells. All four patients had elevated serum phytanic acid concentrations (0.3 to 2.7 mg/dl, normal less than 0.2 mg/dl) and deficient fibroblast phytanic acid oxidase activity (0.1 to 6.7 pmol/mg protein/hr, normal 23 to 87 pmol/mg protein/hr). Serum pipecolic acid was 7 to 55 times normal, and the ratio of C26/C22 very long chain fatty acids was increased (0.10 to 0.22; normal less than 0.03). This characteristic syndrome has been described in several children and called infantile Refsum disease or phytanic acid storage disease. Its relationship to neonatal adrenoleukodystrophy, hyperpipecolic acidemia, and Zellweger syndrome is discussed.
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PMID:Dysmorphic syndrome with phytanic acid oxidase deficiency, abnormal very long chain fatty acids, and pipecolic acidemia: studies in four children. 241 87

Nine cases of neonatal adrenoleukodystrophy are described. All patients had abnormal facial features, moderate to severe hypotonia, hepatomegaly, and retinitis pigmentosa. The clinical course was rapidly progressive in six cases and more protracted in three others. Biological signs of adrenal insufficiency were present in five cases. CT scan showed a demyelinating process in four patients. Trilamellar inclusions were found in the liver of four cases and dark and complex lipidic inclusions in three other cases. In the three necropsied patients there was severe alteration of the white matter involving particularly the cerebellum in two cases. Gyral and cytoarchitectonic disturbances were absent in all three cases. Increased plasma levels of very long chain fatty acids (8/8), phytanic acid (7/8) and bile fluid trihydroxycoprostanic acid (2/4) confirmed the deficiency of multiple peroxisomal enzymes. Clinical, histopathological and biochemical findings of these nine cases are compared to those reported in other neonatal adrenoleukodystrophy cases and to those of other neonatal peroxisomal disorders, that is cerebro-hepato-renal syndrome of Zellweger and infantile Refsum's disease.
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PMID:Neonatal adrenoleukodystrophy. 242 Sep 40

Infantile Refsum's disease was diagnosed in three male patients, presenting with facial dysmorphia, retinitis pigmentosa, neurosensory hearing loss, hepatomegaly, osteopenia and delayed growth and psychomotor development. An elevated plasma phytanic acid concentration and a deficient phytanic acid oxidase activity in fibroblasts were found with an accumulation of very long chain fatty acids in plasma and fibroblasts. There were elevated pipecolic acid levels in plasma, urine and CSF, and abnormal bile acid metabolites in plasma. Deficient activity of acylCoA: dihydroxyacetone phosphate acyl transferase was found in thrombocytes and fibroblasts of these patients as well as an impaired de novo plasmalogen biosynthesis in fibroblasts. These biochemical abnormalities, previously described in the Zellweger syndrome, suggest multiple peroxisomal dysfunction in our patients.
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PMID:Infantile Refsum's disease: biochemical findings suggesting multiple peroxisomal dysfunction. 242 95

An 18-month-old infant presented with a history of arrest of neurological development from the age of eight months, with progressive ataxia, deafness, retinitis pigmentosa and hepatomegaly. Biochemical investigations revealed an elevated plasma phytanic acid level and deficiency of phytanic acid oxidase in skin fibroblasts. Histopathological findings in a liver biopsy were similar to those reported in infantile phytanic acid storage disease. Unexpected findings were the presence of elevated levels of plasma pipecolic acid, and elevated plasma long-chain fatty acid ratios, biochemical findings previously considered to be diagnostic of Zellweger's hepato-cerebro-renal syndrome, and of adrenoleucodystrophy, respectively. Recent biochemical evidence suggests that this patient, and other similar cases that have recently come to our attention, may have a fundamental defect in the peroxisomal enzyme system.
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PMID:Infantile Refsum's disease: a peroxisomal storage disorder? 243 38

Three patients affected by infantile Refsum disease are described with mental retardation, minor facial dysmorphia, chorioretinopathy, sensorineural hearing deficit, hepatomegaly, failure to thrive and hypocholesterolaemia. Initially, only an accumulation of phytanic acid was thought to be present. More recent findings showed a biochemical profile very similar to that found in classical Zellweger syndrome or neonatal adrenoleukodystrophy. Morphologically typical peroxisomes were absent in the liver. All three disorders are associated with multiple peroxisomal dysfunction. Because of these similarities pertinent clinical data of our three patients are compared with those of reported patients diagnosed as having infantile Refsum disease, neonatal adrenoleukodystrophy or Zellweger syndrome who survived for several years. Attention is drawn to the difference in severity of clinical features, ranging from infantile Refsum's disease to neonatal adrenoleukodystrophy and, finally, to Zellweger syndrome.
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PMID:Infantile Refsum disease: an inherited peroxisomal disorder. Comparison with Zellweger syndrome and neonatal adrenoleukodystrophy. 244 76

Progresses in biochemistry permit one to distinguish three biochemical forms of Zellweger Syndrome: 1) hyperpipecolic acidemia, 2) neonatal adrenoleukodystrophy, and 3) infantile Refsum's disease, which have similar clinical manifestations. A seven-month-old male patient with Zellweger Syndrome is presented. He had absence of peroxismes in the liver and elevated pipecolic acids and abnormal levels of bile acids in the blood. The child had a typical neurologic clinical manifestation with hepatomegaly. The ophthalmoscopy revealed grey disks and retinitis pigmentosa with extinguished ERG and law and delayed VEP. The importance of the constant retinal involvement in Zellweger Syndrome is discussed.
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PMID:Zellweger syndrome, retinal involvement. 262 5

A male infant with glutaric aciduria II secondary to electron transfer flavoprotein: ubiquinone oxidoreductase deficiency is compared to previously reported cases of glutaric aciduria II. A common pattern of anomalies in patients with malformations (8/16) includes macrocephaly, large anterior fontanelle, high forehead, flat nasal bridge, telecanthus, and malformed ears. Abnormalities such as hypotonia, cerebral gliosis, heterotopias, hepatomegaly, hepatic periportal necrosis, polycystic kidneys, and genital defects in glutaric aciduria II are reminiscent of those in Zellweger syndrome, whereas elevations of glutaric, ethylmalonic, adipic, and isovaleric acids are quite distinctive. A unique ultrastructural alteration of the glomerular basement membrane was observed in the proposita. This manifestation may represent an early stage in renal cyst formation and provide a diagnostic criterion for glutaric aciduria II when enzyme studies are unavailable.
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PMID:Glutaric aciduria type II: review of the phenotype and report of an unusual glomerulopathy. 265 91


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