C282Y and H63D mutations of the haemochromatosis gene in patients with iron overload.

OBJECTIVE: To determine the relevance of C282Y and H63D mutations of HEF gene in patients with iron overload. PATIENTS AND METHODS: Patients with iron overload referred to our Liver Unit were included in the study. The association of mutations to different diagnosis and their impact on the severity of the hepatopathy were explored. Sensitivity, specificity and positive and negative predictive values of mutations for the diagnosis of haemochromatosis were determined. RESULTS: The study included 78 patients with iron overload. The control group included 21 patients of similar age and sex ratio without iron overload nor hepatopathy. Twenty three patients had haemochromatosis, 22 alcoholic liver disease and 33 other diseases unrelated to iron metabolism. Seventy three per cent of patients with haemochromatosis were homozygous for the C282Y mutation. All the C282Y homozygous subjects had also haemochromatosis. Fifty three per cent of patients with alcoholic hepatopathy had some kind of mutation. This has been also observed in 70% of patients with iron-unrelated diseases. Such percentage was significantly greater than in the control group (24% with H63D mutation). C282Y homozygosity in patients with iron overload had a sensitivity of 73.9%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 89.6%. CONCLUSIONS: In our population, as in all the Western countries, haemochromatosis is mainly associated to homozygous C282Y mutation. The high frequency of mutations in patients with iron overload and without haemochromatosis suggests the involvement of such mutations in iron overload.

[Multiple hepatic focal nodular hyperplasia: its presentation in childhood and atypical evolution]. / Hiperplasia nodular focal múltiple hepática: presentación en la infancia y evolución atípica.

Multiple focal nodular hyperplasia is an uncommon benign liver tumor although its incidence has been increasing in the last few years. A case of focal nodular hyperplasia in a young woman is described, which was discovered in infancy and which presented two nodules in each lobe. The diagnosis was subsequently confirmed by large surgical biopsy. Conservative therapy was given for 16 years during which time there was progressive tumor growth, increase of pain and cholestatic enzymes. The unusual presentation this benign lesion may have, a strategy for its diagnosis and the generally conservative management that is currently favored are discussed.

[Spontaneous bacterial peritonitis caused by Listeria monocytogenes]. / Peritonitis bacteriana espontánea por Listeria monocytogenes.

We present a 68 year old male with alcoholic cirrhosis that was admitted with abdominal pain and fever. Hepatocarcinoma and spontaneous bacterial peritonitis by Listeria monocytogenes was diagnosed. The patient was treated with ampicillin and tobramycin during 25 days following a favorable course although ascitic fluid remained abnormal during 21 days. It is noted the rarity of Listeria as a cause of bacterial peritonitis in cirrhotic patients although they are immunodeficient. It is also important to establish the etiological origin because standard treatment of spontaneous bacterial peritonitis is cefotaxime and Listeria is resistant to this antibiotic. The 66% of spontaneous bacterial peritonitis secondary to Listeria monocytogenes infection in cirrhotic patients has been reported in Spain and this might be due to a higher incidence of human listeriosis in this country.

[Systemic amyloidosis presenting as cholestatic jaundice]. / Ictericia colestásica como forma de presentación de una amiloidosis sistémica.

We present a case of a 68 year old man with general deterioration and recent onset of jaundice that was admitted for clinical evaluation. Previous records were: treated bone tuberculosis, hypertrophic myocardiopathy and ischemic cardiopathy. Physical examination showed liver enlargement without evidence of chronic liver disease. Laboratory studies and other explorations such as abdominal ultrasound, CAT and ERCP did not leed to an objective diagnosis. Therefore, a liver biopsy was performed, showing liver amyloidosis AA type with amyloid deposits in portal spaces. The patient died three months later. The rarity of this clinical presentation is discussed and its poor prognosis outlined. Some peculiarities of liver deposits are reviewed.

[Acetylation polymorphism in lung cancer]. / Polimorfismo acetilador en el cáncer de pulmón.

The acetylation phenotype was determined, by means of sulfamethazine measurement, in 87 patients (83 male) with confirmed bronchogenic carcinoma and in 93 healthy control patients (41 male) of equal ages. 48 patients and 54 controls were classified as being "slow acetylators" (Ch2 n.s.) When the persons were individually analysed by phenotype, it was confirmed that the patients showed a significantly lower rate of acetylated sulfamethazine than the control group (p less than 0.02), owing to the poor acetylation of patients with small-cell lung cancer. This difference should be confirmed by more detailed pharmacokinetic studies before regarding it as a possible interference of paraneoplasic type. The polymorphism acetylator cannot be considered a genetic marker related to the risk of having lung cancer.

Polymorphic oxidation of debrisoquine in bladder cancer.

The oxidative polymorphism of debrisoquine has been determined in 125 patients with bladder cancer and in 556 healthy control subjects; 96.6% of patients and 93.9% of controls with a metabolic ratio of debrisoquine less than 12.6 were classified as extensive metabolizers of debrisoquine (P = NS). The distribution of frequencies of metabolic ratio values tended to have lower values in the patients (P less than 0.05), reflecting a higher oxidative rate of debrisoquine in urothelioma patients that cannot be explained solely in terms of enzymatic induction by drugs, tobacco or alcohol. Patients with a high occupational risk for urothelioma had lower metabolic ratio values (P = 0.03). Our results suggest that oxidative polymorphism of debrisoquine might be related to the pathogenesis of bladder cancer.

Acetylator polymorphism in Parkinson's disease.

Acetylator phenotype has been determined using sulphamethazine in 100 patients with Parkinson's disease and in 93 age-matched normal control subjects. Sixty-nine patients and 54 control subjects were classified as slow acetylators (NS). No relation was found among acetylator polymorphism and age at onset or clinical stage of disease. Amongst slow acetylators, the percentage of acetylated sulphamethazine in plasma was significantly lower in patients than in controls. Despite this finding, the results do not support any relationship between acetylator polymorphism and the risk of developing Parkinson's disease.

Acetylator phenotype in psoriasis.

Acetylator phenotype has been determined with sulfamethazine in 64 psoriatic patients and in 157 normal control subjects. Forty patients (62.5%) versus 90 control subjects (57.3%) were slow acetylators (p = NS). However, 81% of the 27 patients with psoriatic siblings were slow acetylators (p less than 0.05). Slow acetylator phenotype may be a genetic risk factor for the development of psoriasis.