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)

Five unrelated patients with protoporphyria (PP) had diagnostic liver biopsies performed to assess the degree of liver damage. The porphyrin content of the liver was quantitated and characterized and liver damage was assessed. Ultraviolet (UV) microscopy was performed in each case. Liver structure was assessed by light, polarization and electron microscopy. In 3 patients the liver was visualized directly before biopsy through a peritoneoscope. Liver damage ranged from minimal cell necrosis to portal fibrosis; the latter was observed in a 27-year-old sib of a patient (M.I.) who had died, aged 29, 3 years previously in liver failure from PP-related cirrhosis. Liver tissue from the latter patient which was obtained at the time of autopsy was re-examined by light and polarization microscopy. Hepatic pigment deposits, thought to be lipofuscin, showed birefringence on polarization microscopy in two cases, one of them being patient M.I. with PP-cirrhosis. Liver fluorescence on UV microscopy was centrizonal, punctate, faded rapidly and was easily distinguishable from that seen in porphyria cutanea tarda (PCT). The porphyrin content of the liver tissue in biopsied patients was between 5 mug and 80 mug, and in the autopsy case 1600 mug protoporphyrin/g wet weight liver, and on thin layer chromatography only dicarboxylic porphyrins were demonstrable. Hepatic cytochrome P-450 levels in protoporphyria were within normal range. Vmax and Km for aminopyrine-N-demethylation and benzpyrene hydroxylation did not differ significantly from our findings in PCT, variegate porphyria in remission and in non-porphyric controls. However, the activity of hepatic delta-aminolaevulinic acid (ALA) synthetase was significantly enhanced in 2 of the 3 patients in whom this measurement was performed.
 ...
PMID:The hepatic lesion in protoporphyria (PP): preliminary studies of haem metabolism, liver structure and ultrastructure. 100 82

A patient with cavitary tuberculosis, hepatic cirrhosis, bullous skin lesions over sun-exposed surfaces, disorientation, and a chronic, as well as recent, history of illicit alcohol consumption was found to have acute variegate porphyria by characteristic fecal and urinary porphyrin studies. Elevated levels of lead and arsenic were found in serum and urine without evidence of heavy metal storage in hair and liver. We suspect that the variegate porphyria was precipitated by the ingestion of heavy metals contained in illicit alcohol. In a patient with disorientation, bullous skin lesions, and a history of illicit alcohol ingestion, one must consider heavy metal intoxication and secondary porphyrin abnormalities.
 ...
PMID:Variegate porphyria and heavy metal poisoning from ingestion of "moonshine". 687 66

Porphyrias are divided into erythropoietic and hepatic manifestations. Erythropoietic porphyrias are characterized by cutaneous symptoms and appear in early childhood. Erythropoietic protoporphyria is complicated by cholestatic liver cirrhosis and progressive hepatic failure in 10%, of patients. Acute hepatic porphyrias (delta-aminolaevulinic acid dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria and variegate porphyria) are characterized by variable extrahepatic gastrointestinal, neurological-psychiatric and cardiovascular manifestations requiring early diagnosis to avoid life-threatening complications. Acute hepatic porphyrias are pharmacogenetic and molecular regulatory diseases (without porphyrin accumulation) mainly induced by drugs, sex hormones, fasting or alcohol. The disease process depends on the derepression of hepatic delta-aminolaevulinic acid synthase following haem depletion. In contrast to the acute porphyrias, nonacute, chronic hepatic porphyrias such as porphyria cutanea tarda are porphyrin accumulation disorders leading to cutaneous symptoms associated with liver disease, especially caused by alcohol or viral hepatitis. Alcohol, oestrogens, haemodialysis, hepatitis C and AIDS are triggering factors. Porphyria cutanea tarda is the most common porphyria, followed by acute intermittent porphyria and erythropoietic protoporphyria. The molecular genetics of the porphyrias is very heterogenous. Nearly every family has its own mutation. The mutations identified account for the corresponding enzymatic deficiencies, which may remain clinically silent throughout life. Thus, the recognition of the overt disorder with extrahepatic manifestations depends on the demonstration of biochemical abnormalities due to these primary defects and compensatory hepatic overexpression of hepatic delta-aminolaevulinic acid synthase in the acute porphyrias. Consequently, haem precursors are synthesized in excess. The increased metabolites upstream of the enzymatic defect are excreted into urine and faeces. The diagnosis is based on their evaluation. Primary enzymatic or molecular analyses are noncontributary and may be misleading. Acute polysymptomatic exacerbations accompany a high excretory constellation of porphyrin precursors delta-aminolaevulinic acid and porphobilinogen. Homozygous or compound heterozygous variants of acute hepatic porphyrias may already manifest in childhood.
 ...
PMID:Erythropoietic and hepatic porphyrias. 1111 26

Porphyrias are a heterogenous group of diseases that may result in disabling or life threatening neurovisceral symptoms and/or cutaneous photosensitivity. In acute intermittent porphyria, the clinical features, particularly neurological symptoms, may be life-threatening and disabling. Conventional treatment with human hemin, though effective in reducing symptoms, does not reverse neuropathy when structural nerve damage has occurred and may cause intense phlebitis. Liver transplantation (LT) may be considered as treatment for those with repeated life-threatening acute attacks resulting in poor quality of life, requirement of ventilatory support, and progressive loss of venous access due to hemin infusion. Patients with variegate porphyria (VP) present after puberty with neurovisceral symptoms and skin manifestations. LT resolved VP in the 1 patient reported in the literature. Aminolaevulinic acid dehydratase deficient porphyria is a rare autosomal recessive disorder and a child who presented with failure to thrive and required transfusions and parenteral nutrition did not improve with LT. In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin in the bone marrow. Protoporphyrin is hepatotoxic and pigment loading of hepatocytes and bile canalicular sludging may result in progressive cholestasis and cirrhosis. LT is beneficial for such patients with end-stage liver disease. Perioperative management includes use of filters on operative lights to prevent skin burns and intestinal perforation. Other concerns include development of neuropathy, biliary complications, and recurrent liver disease. This review addresses the rationale, patient selection, evaluation, management issues, and technique of performing LT in various types of porphyria.
 ...
PMID:Liver transplantation for porphyria: who, when, and how? 1776 98