Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infantile Refsum's disease (IRD) is a peroxisomal deficiency disease which is closely related to neonatal adrenoleukodystrophy (NALD) and the Zellweger syndrome (ZS). Recent observations suggest that NALD and ZS are separate genetic disorders but the delimitation towards IRD remains uncertain. We present here the first autopsy report of a patient who was clinically and biochemically diagnosed as having IRD, and we compare the findings with those from NALD and ZS. The main gross and microscopic findings comprised micronodular liver cirrhosis, small hypoplastic adrenals without degenerative changes, and large groups of lipid macrophages in liver, lymph nodes and certain areas of the cerebral white matter. The brain showed no malformations except for a severe hypoplasia of the cerebellar granule layer and ectopic location of the Purkinje cells in the molecular layer. A mild and diffuse reduction of axons and myelin was found in the corpus callosum and periventricular white matter, the corticospinal tracts, and the optic nerves. Large numbers of perivascular macrophages were present in the same areas but there was no active demyelination. The retina and cochlea showed severe degenerative changes. Peripheral nerves, skeletal system and kidneys were normal. Electron microscopy showed characteristic cytoplasmic inclusions with bilamellar profiles in macrophages in the liver, lymph nodes and brain but not in the adrenals. Similar inclusions were found in liver cells and astrocytes. The findings differ from ZS which shows cortical renal cysts, skeletal changes, liver changes, cerebral micropolygyria, neuronal heterotopias, and demyelination of the white matter. Cases with NALD show mild cerebral malformations, active demyelination, degenerative changes of the adrenals, liver changes, and bilamellar electromicroscopic inclusions in macrophages. Our cases thus resembled NALD but lacked active demyelination, cerebral cortical malformations and adrenal degenerative changes. Further autopsy studies will be necessary to determine whether these changes are consistent findings in IRD.
 ...
PMID:Infantile Refsum's disease: a generalized peroxisomal disorder. Case report with postmortem examination. 245 20

Peroxisomes or microbodies are peculiar subcellular organelles with an important role in the metabolism of a variety of different organic compounds. Particularly they are an important site of bile acids synthesis. Some hepatic diseases, mainly cholestatic, can to be reconnected at disorders of bile acids synthesis by these organelles. From the biochemical point some diseases present alterations of the cholesterol side chain (Zellweger syndrome, pseudo-Zellweger syndrome, infantile Refsum's disease, neonatal adrenoleukodystrophy), other diseases present errors involving the steroid nucleus (familial giant cell hepatitis). Zellweger disease or cerebro-hepato-renal syndrome is characterized clinically by skeletal changes, muscle hypotonia, renal cysts, psychosomatic retardation and persistent cholestasis and from the ultrastructural standpoint by the virtual absence of liver cell peroxisomes. Pseudo-Zellweger disease shows many of the clinical features of Zellweger disease but differs from this condition on account of the presence of abundant peroxisomes in the liver cells. Infantile Refsum's disease and neonatal adrenoleukodystrophy show typical clinical disorders and liver damage leading to cirrhosis. "Familial giant cell hepatitis" is characterized by jaundice from the first days of life, hepatosplenomegaly, cholestasis, lack of physical malformations. The disorder is due to defective biosynthesis of the bile acids with formation of allo-bile acids.
 ...
PMID:[Liver pathologies due to peroxisome disorders]. 818 91