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

Four cases of neonatal haemochromatosis presenting as fulminant hepatic failure in the newborn were diagnosed by autopsy. In all four cases the diagnosis was made by histochemical demonstration of excessive iron deposition in hepatocytes and extrahepatic parenchymal cells, particularly pancreatic acinar epithelium, thyroid follicular epithelium and distal renal tubules. No haemosiderin was detectable in the extrahepatic mononuclear-phagocytic cells of the spleen, lymph nodes and bone marrow. The liver was the most severely affected organ. The hepatic haemosiderosis was associated with massive hepatocellular necrosis of prenatal onset in three patients, one of whom showed formation of regenerative nodules, establishing true congenital cirrhosis. Other inconstant findings included giant cell transformation, diffuse sinusoidal fibrosis with segregation of small groups of hepatocytes and cholestasis with pseudoacinar change of liver cell plates. The fetal liver disease had its onset in the late second trimester of pregnancy and was reflected clinically by severe panhypoproteinaemia with non-immune hydrops; hyperbilirubinaemia and haemorrhagic diatheses were apparent in the newborn. Neonatal haemochromatosis is a metabolic disorder, probably of autosomal recessive inheritance. The site and nature of the basic defect remain uncertain. Pathologists should be aware of this condition and its potential recurrence in subsequent pregnancies.
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PMID:Neonatal haemochromatosis. 225 73

Neonatal haemochromatosis is a disorder which affects foetuses and newborns. It is characterized by hepatocellular insufficiency, often appearing on the first day of life in the form of coagulopathy, hypoalbuminemia, hypoglycemia and jaundice. While spontaneous recovery has been reported, most of these infants die, and the diagnosis was previously often made during autopsy. With the help of MRI and salivary gland biopsies, plus increasing awareness of this disorder, the diagnosis is now often made quite early, and successful liver transplantations have been reported. Recently, there have also been encouraging preliminary reports of successful intervention with antioxidant and chelation pharmacotherapy, using a combination of selenium, vitamin E, N-acetylcysteine, deferoxamine, and prostaglandin E. We describe two patients with neonatal haemochromatosis who were both treated with this new "cocktail", one of whom died at five days of age, while the other survived, but needed a liver transplant at 2 1/2 months of age. The pathology of this condition is characterized by hepatic cirrhosis with giant cell transformation, and by siderosis of extrahepatic tissues. The prognosis is poor, and our experience with antioxidant treatment has been disappointing. Liver transplantation is a therapeutic option, but its use is limited by the scarcity of donor organs and the small size of many of the patients.
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PMID:[Neonatal hemochromatosis]. 954 1

Neonatal haemochromatosis (NH) is a severe and newly recognised syndrome of uncertain aetiology, characterised by congenital cirrhosis or fulminant hepatitis and widespread tissue iron deposition. NH occurs in the context of maternal disease including viral infection, as a complication of metabolic disease in the fetus, and sporadically or recurrently, without overt cause, in sibs. Although an underlying genetic basis for NH has been suspected, no test is available for predictive analysis in at risk pregnancies. As a first step towards an understanding of the putative genetic basis for neonatal haemochromatosis, we have conducted a systematic study of the mode of transmission of this disorder in a total of 40 infants born to 27 families. We have moreover carried out a molecular analysis of candidate genes (beta(2)-microglobulin, HFE, and haem oxygenases 1 and 2) implicated in iron metabolism. No pathogenic mutations in these genes were identified that segregate consistently with the disease phenotype in multiplex pedigrees. However, excluding four pedigrees with clear evidence of maternal infection associated with NH, a pedigree showing transmission of maternal antinuclear factor and ribonucleoprotein antibodies to the affected infants, and two families with possible matrilineal inheritance of disease in maternal half sibs, a large subgroup of the affected pedigrees point to the inheritance of an autosomal recessive trait. This included 14 pedigrees with affected and unaffected infants and a single pedigree where all four affected infants were the sole offspring of consanguineous but otherwise healthy parents. We thus report three distinct patterns of disease transmission in neonatal haemochromatosis. In the differentiation of a large subgroup showing transmission of disease in a manner suggesting autosomal recessive inheritance, we also provide the basis for further genome wide studies to define chromosomal determinants of iron storage disease in the newborn.
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PMID:Classification and genetic features of neonatal haemochromatosis: a study of 27 affected pedigrees and molecular analysis of genes implicated in iron metabolism. 1154 28

Juvenile hemochromatosis (JH) is an autosomal recessive disease causing iron overload before age 30 in both sexes. JH is characterised by hypogonadism, growth retardation and cardiomyopathy. Linkage of JH to chromosome lq is established in pedigrees throughout Europe. Studies of 29 patients in 20 families of diverse ethnic origin confirm early-onset iron overload. Neonatal hemochromatosis (NH) is a syndrome of unknown origin characterized by congenital cirrhosis or fulminant hepatitis with hepatic and extra-hepatic iron deposits. We assessed 40 infants from 27 families and identified 3 patterns of disease transmission. In 12 of the 27 there was >1 affected infant and in 5 families all infants were affected by NH. In 19 families unaffected children were also born. In 4 families there was bacterial or viral maternal infection associated with NH. In two families, antibodies to DNA or ribonuclear proteins were identified. In 12 families, unaffected children were born to the same parents in the absence of maternal antibodies or infection and without indications of maternal transmission. Consanguinity was observed in 1 family with 4 affected offspring (1 stillbirth + 3 neonatal deaths). Sequence analysis of HFE, beta2M, and both human heme oxygenase genes failed to identify any causal mutations in nuclear NH families but our study points to the existence of a cohort of patients likely to suffer from an autosomal recessive trait. A genome wide scanning study is underway to identify the putative locus.
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PMID:Hemochromatosis--neonatal and young subjects. 1254 31

Syndromic diarrhea (SD), also known as phenotypic diarrhea (PD) or tricho-hepato-enteric syndrome (THE), is a congenital enteropathy presenting with early-onset of severe diarrhea requiring parenteral nutrition (PN). To date, no epidemiological data are available. The estimated prevalence is approximately 1/300,000-400,000 live births in Western Europe. Ethnic origin does not appear to be associated with SD. Infants are born small for gestational age and present with facial dysmorphism including prominent forehead and cheeks, broad nasal root and hypertelorism. Hairs are woolly, easily removed and poorly pigmented. Severe and persistent diarrhea starts within the first 6 months of life (</= 1 month in most cases) and is accompanied by severe malabsorption leading to early and relentless protein energy malnutrition with failure to thrive. Liver disease affects about half of patients with extensive fibrosis or cirrhosis. There is currently no specific biochemical profile, though a functional T-cell immune deficiency with defective antibody production was reported. Microscopic analysis of the hair show twisted hair (pili torti), aniso- and poilkilotrichosis, and trichorrhexis nodosa. Histopathological analysis of small intestine biopsy shows non-specific villous atrophy with low or no mononuclear cell infiltration of the lamina propria, and no specific histological abnormalities involving the epithelium. The etiology remains unknown. The frequent association of the disorder with parental consanguinity and/or affected siblings suggests a genetic origin with an autosomal recessive mode of transmission. Early management consists of total PN. Some infants have a rather milder phenotype with partial PN dependency or require only enteral feeding. Prognosis of this syndrome is poor, but most patients now survive, and about half of the patients may be weaned from PN at adolescence, but experience failure to thrive and final short stature. DISEASE NAME AND SYNONYMS: Syndromic diarrhea - Phenotypic diarrhea - Tricho-hepato-enteric syndrome - Intractable diarrhea of infancy with facial dysmorphism - Trichorrhexis nodosa and cirrhosis - Neonatal hemochromatosis phenotype with intractable diarrhea and hair abnormalities - Intractable infant diarrhea associated with phenotypic abnormalities and immune deficiency.
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PMID:Syndromic (phenotypic) diarrhea in early infancy. 1830 70

Neonatal hemochromatosis (NH) is a clinical syndrome consisting of liver disease and pathologic siderosis of various extrahepatic tissues. NH is a form of secondary hemochromatosis in which severe fetal liver injury causes iron overload due to poor regulation of maternofetal iron flux. Gestational alloimmune liver disease (GALD) has been established as the cause of fetal liver injury resulting in nearly all cases of NH. In GALD, sensitization of some women to a fetal liver antigen results in development of specific antifetal liver IgG antibodies. When delivered to the fetal circulation these antibodies bind to the antigen and activate the terminal complement cascade resulting in hepatocyte injury and death. GALD may produce subacute and chronic fetal liver injury (congenital cirrhosis) typical of NH. It may also produce acute injury and acute liver failure of the fetus and newborn, often with no iron overload or siderosis.
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PMID:Gestational alloimmune liver disease and neonatal hemochromatosis. 2339 33

Neonatal hemochromatosis is a clinical condition in which severe liver disease in the newborn is accompanied by extrahepatic siderosis. Gestational alloimmune liver disease (GALD) has been established as the cause of fetal liver injury resulting in nearly all cases of NH. In GALD, a women is exposed to a fetal antigen that she does not recognize as "self" and subsequently begins to produce IgG antibodies that are directed against fetal hepatocytes. These antibodies bind to fetal liver antigen and activate the terminal complement cascade resulting in hepatocyte injury and death. GALD can cause congenital cirrhosis or acute liver failure with and without iron overload and siderosis. Practitioners should consider GALD in cases of fetal demise, stillbirth, and neonatal acute liver failure. Identification of infants with GALD is important as treatment is available and effective for subsequent pregnancies.
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PMID:Neonatal hemochromatosis. 2575 19