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)

This report describes a patient not suspected of having Klinefelter syndrome during life but diagnosed with it following postmortem examination using fluorescent in situ hybridization (FISH) for sex chromosomes and hormone serum analysis. A 49-year-old Japanese man had a history of nephrosis, heavy alcohol consumption, diabetes mellitus, and liver cirrhosis and had been undergoing dialysis for 10 years. He died of ruptured esophageal varices. Autopsy revealed hypogonadism, suggesting Klinefelter syndrome. This was confirmed by FISH, which showed a mosaic 46XY, 47XXY karyotype, and by serum analysis, which revealed high luteinizing hormone and follicle-stimulating hormone and low testosterone levels. Autopsy also revealed a nodular, bilateral, testicular Leydig cell hyperplasia. This report illustrates the value of postmortem laboratory investigations, particularly FISH for sex chromosomes and serum hormone analysis, for the demonstration of clinically uncertain or "occult" Klinefelter syndrome.
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PMID:Postmortem diagnosis of "occult" Klinefelter syndrome in a patient with chronic renal disease and liver cirrhosis. 1186 Mar 15

Juvenile haemochromatosis or haemochromatosis type 2 is a rare autosomal recessive disorder which causes iron overload at a young age, affects both sexes equally and is characterized by a prevalence of hypogonadism and cardiopathy. Patients with haemochromatosis type 2 have been reported in different ethnic groups. Linkage to chromosome 1q has been established recently, but the gene remains unknown. We report the analysis of the phenotype of 29 patients from 20 families of different ethnic origin with a juvenile 1q-associated disease. We also compared the clinical expression of 26 juvenile haemochromatosis patients with that of 93 C282Y homozygous males and of 11 subjects with haemochromatosis type 3. Patients with haemochromatosis type 2 were statistically younger at presentation and had a more severe iron burden than C282Y homozygotes and haemochromatosis type 3 patients. They were more frequently affected by cardiopathy, hypogonadism and reduced glucose tolerance. In contrast cirrhosis was not statistically different among the three groups. These data suggest that the rapid iron accumulation in haemochromatosis type 2 causes preferential tissue damage. Our results clarify the natural history of the disease and are compatible with the hypothesis that the HFE2 gene has greater influence on iron absorption than other haemochromatosis-associated genes.
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PMID:Natural history of juvenile haemochromatosis. 1206 Jan 40

Iron overload in body tissues can cause complications such as cirrhosis, cardiomyopathy, diabetes, hypogonadism and arthritis. In populations of northern European descent, most iron overload is due to hereditary haemochromatosis (HHC), a genetic condition that causes increased iron absorption. HHC can be treated or prevented by regular phlebotomy treatments. Some experts have called for population screening for HHC, so that early phlebotomy treatment can be initiated. Two screening tests are available: measurement of the serum iron transferrin saturation (Tf%) and genetic testing for HFE mutations. However, both methods have low positive predictive values. Current data suggest that most people at risk are unlikely to develop clinical symptoms and that the population prevalence of clinical complications of HHC is low, arguing against population screening. Two other prevention strategies are available. (1) Health provider education, to heighten awareness of HHC as an explanation for symptoms and signs seen in early iron overload including unexplained fatigue, joint pain, palpitations, abdominal pain, elevated liver function tests, hepatomegaly and elevated serum ferritin. (2) Family-based testing after a diagnosis of HHC, to ensure that relatives are evaluated for evidence of iron overload. More research is also needed to identify the factors that increase risk for disease in persons with excess iron uptake, to determine whether moderate iron overload is a health risk and to evaluate the causes of iron overload other than HHC.
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PMID:Hereditary haemochromatosis: a realistic approach to prevention of iron overload disease in the population. 1240 10

We report clinical and genetic characteristics of seven juvenile hemochromatosis (JH) patients (six females, one male) in two unrelated kinships from the southeastern U.S. All had severe iron overload. Mean age at diagnosis was 20 +/- 5 years (range 8-23 years). In six patients, the mean age at onset of signs and symptoms attributable to iron overload was 15 +/- 2 years (12-18 years); an 8-year-old girl had no symptoms. Six of the seven patients had hypogonadotrophic hypogonadism, two had severe cardiomyopathy, seven had hepatomegaly, two had hepatic cirrhosis, and five had hyperpigmentation. Two of four siblings with JH also had Hashimoto thyroiditis. One patient with severe cardiomyopathy improved with therapeutic phlebotomy, medical therapy for congestive heart failure, and a permanent pacemaker; the other died before phlebotomy was initiated. Estimates of average daily iron absorption before phlebotomy-induced iron depletion were 2.3, 3.1, and 1.7 mg in a male and two females, respectively. Both parents of four siblings with JH were heterozygous at two Ch1q loci (D1S1156, D1S2344); each of the four affected siblings was homozygous at both loci. An unaffected sib was heterozygous at D1S1156. One patient was heterozygous for HFE H63D, five others did not have HFE C282Y or H63D, and one was unavailable for testing. We conclude that JH occurs in the southeastern U.S. It is likely that JH allele(s) in at least one of the present kinships occur(s) on Ch1q, and presumably this represents a mutation(s) of the same gene localized to Ch1q in Italian and Greek JH kindreds. The present cases do not have HFE genotypes typical of hemochromatosis diagnosed in adults. Hashimoto thyroiditis, linked to Ch6p in many kinships, did not segregate with JH alleles on Ch1q in the present kinship.
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PMID:Juvenile hemochromatosis in the southeastern United States: a report of seven cases in two kinships. 1248 11

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

Four types of hereditary haemochromatosis have been identified. Type 1 is due to a point mutation in the HFE gene (C282Y) and leads via an increase in intestinal iron absorption to iron overload and organ damage. Type 2 is a juvenile form with manifestation before age 30; it affects both gender and is associated with severe cardiomyopathy and hypogonadism. The genetic defect of type 3 is located on chromosome 7q22 and affects the transferrin receptor 2. The consequences of type 3 are similar to those of type 1. The autosomal-dominant type 4 is located on chromosome 2q32 and affects the basolateral iron carrier ferroportin 1. In contrast to types 1 and 3 iron deposits in type 4 are seen predominantly in macrophages; in type 4 serum ferritin is significantly increased although transferrin saturation is only slightly abnormal. The prognosis of haemochromatosis is normal when phlebotomy therapy is started prior to manifestation of cirrhosis or diabetes. Screening strategies should be implemented to improve early detection.
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PMID:[Hereditary hemochromatosis]. 1267 39

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autosomal-recessive syndrome defined by two of the following conditions: chronic mucocutaneous candidiasis, hypoparathyroidism, or Addison's disease. Other autoimmune conditions may be associated, such as hypothyroidism, hypogonadism, insulin-dependent diabetes mellitus, chronic active hepatitis, pernicious anemia, vitiligo, alopecia, biliary cirrhosis, and ectodermal dysplasia. APECED is caused by mutations in the autoimmune regulator gene, mapping to 21q22.3. We report on three patients whose clinical and molecular features challenge the currently used diagnostic criteria for APECED. AR presented at 15 yr of age with a history of recurrent infections and mucocutaneous candidiasis. He is now 21 yr old, and no other signs or symptoms of APECED have appeared to date. DR presented at 7 yr of age with hypocalcemia and a prolonged Q-T interval on the electrocardiogram. He also had minor facial dysmorphisms and mild mental retardation. Serum calcium levels were low, PTH levels were undetectable, and hypoparathyroidism was therefore diagnosed. All other biochemical, immunological, and endocrinological tests were normal. DR is now 8 yr old with no other signs or symptoms of APECED. ST presented at 14 yr of age for alopecia aerata and pitted nail dystrophy and goiter. Thyroid function was normal in the presence of thyroid-specific antibodies. No other signs or symptoms of APECED have appeared to date. Genetic analysis revealed a typical mutation (R257X) on a single allele in both AP and DR; in ST, heterozygosity for a novel mutation (V484M) involving one of the zinc fingers of the plant homeodomain of the protein was found. The finding of a typical APECED mutation in two patients presenting with one isolated major clinical APECED feature and of a novel mutation in a patient presenting with atypical features of APECED onset suggests that the time might have come for updating the diagnostic criteria of this syndrome.
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PMID:Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome: time to review diagnostic criteria? 1284 57

This study aimed to assess the clinical, biochemical and hormonal factors contributing to low bone density in a large ambulatory group of patients with cirrhosis of diverse aetiology. Bone density of the lumbar spine, neck of femur, total hip, total body, as well as total body fat, was measured by dual X-ray (DEXA) absorptiometry in 81 men and 32 women (average age 50.3 years). Morning blood and urine samples were taken for hormonal and biochemical analysis. Viral hepatitis was the most common cause of cirrhosis (54%) and the severity of cirrhosis ranged from Child-Pugh A5-C14. Osteoporosis was most common in the lumbar spine but was present at any site in 31% of women and 22% of men, with osteopenia present in another 40% of both genders. Urinary deoxypyridinoline, a marker of bone resorption, was elevated in 56% of patients and was associated with increasing severity of cirrhosis and a higher prevalence of osteoporosis, particularly of the lumbar spine. Hip-bone density was primarily affected by low 25-hydroxyvitamin D levels and was associated with secondary hyperparathyroidism in one third of these patients. Additional important predictors for low bone density at all sites were age in women and testosterone in men. These findings indicate that, although the pathophysiology of osteoporosis in chronic liver disease is heterogeneous, high bone turnover may be the underlying pathophysiological mechanism in a significant subgroup of cirrhotic patients and may reflect metabolic effects of hypogonadism or secondary hyperparathyroidism on bone.
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PMID:The heterogeneity of bone disease in cirrhosis: a multivariate analysis. 1450 96

One of the most common genetic causes of iron overload is hereditary hemochromatosis (HHC), a condition characterized by overabsorption of dietary iron from the gastrointestinal tract. This condition can lead to excessive iron accumulation with resulting dysfunction in multiple organs, including the liver, skin, heart,joints, pancreas, and testes. The clinical consequences of HHC if undetected and untreated can be severe and include liver cirrhosis,hepatocellular carcinoma, diabetes mellitus, cardiac arrhythmias and failure, arthritis, and hypogonadism. HHC is one of the most common heritable conditions in white populations of Northern European origin. This article presents a case study of HHC, describing inheritance and genetics, disease characteristics and natural history, diagnosis, differential diagnosis, and management.
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PMID:Clinical consult: iron overload--hereditary hemochromatosis. 1533 Dec 58

The A16V mitochondrial targeting sequence polymorphism influences the antioxidant activity of MnSOD, an enzyme involved in neutralising iron induced oxidative stress. Patients with hereditary haemochromatosis develop parenchymal iron overload, which may lead to cirrhosis, diabetes, hypogonadism, and heart disease. The objective of this study was to determine in patients with haemochromatosis whether the presence of the Val MnSOD allele, associated with reduced enzymatic activity, affects tissue damage, and in particular heart disease, as MnSOD knockout mice develop lethal cardiomyopathy. We studied 217 consecutive unrelated probands with haemochromatosis, and 212 healthy controls. MnSOD polymorphism was evaluated by restriction analysis. The frequency distribution of the polymorphism did not differ between patients and controls. Patients carrying the Val allele had higher prevalence of cardiomyopathy (A/A 4%, A/V 11%, V/V 30%, p = 0.0006) but not of cirrhosis, diabetes, or hypogonadism, independently of age, sex, alcohol misuse, diabetes, and iron overload (odds ratio 10.1 for V/V, p = 0.006). The frequency of the Val allele was higher in patients with cardiomyopathy (0.67 v 0.45, p = 0.003). The association was significant in both C282Y+/+ (p = 0.02), and in non-C282Y+/+ patients (p = 0.003), and for both dilated (p = 0.01) and non-dilated stage (p = 0.04) cardiomyopathy, but not for ischaemic heart disease. In patients with hereditary haemochromatosis, the MnSOD genotype affects the risk of cardiomyopathy related to iron overload and possibly to other known and unknown risk factors and could represent an iron toxicity modifier gene.
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PMID:The mitochondrial superoxide dismutase A16V polymorphism in the cardiomyopathy associated with hereditary haemochromatosis. 1559 Dec 82


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