Guinea pig transglutaminase immunolinked assay does not predict coeliac disease in patients with chronic liver disease.

BACKGROUND: It has been suggested that serological screening for coeliac disease (CD) should be performed in patients with chronic unexplained hypertransaminasaemia. AIMS: To evaluate the specificity for CD diagnosis of serum IgA antitissue transglutaminase (tTG) determination in consecutive patients with chronic hypertransaminasaemia using the most widely utilised ELISA based on tTG from guinea pig as the antigen. PATIENTS AND METHODS: We studied 98 patients with chronic hypertransaminasaemia, evaluated for the first time in a hepatology clinic. Serum anti-tTG and antiendomysial (EmA) assays were performed. Patients positive for EmA and/or anti-tTG were proposed for intestinal biopsy. Finally, all sera were reassayed for anti-tTG using an ELISA based on human recombinant tTG as the antigen. RESULTS: A total of 94/98 hypertransaminasaemic patients were positive for hepatitis virus markers, with 82/98 (83%) positive for anti-hepatitis C virus. Liver histology showed that most patients had mild or moderate chronic hepatitis while severe fibrosis or overt liver cirrhosis was found in 20/98. CD screening showed that 15/98 (16%) hypertransaminasaemic subjects had anti-tTG values in the same range as CD patients; however, IgA EmA were positive in only 2/98 (2%). Distal duodenal biopsy, performed in nine patients, showed subtotal villous atrophy in the two EmA+/anti-tTG+ patients but was normal in 7/7 EmA-/anti-tTG+ subjects. The presence of anti-tTG+ values in EmA- patients was unrelated to particular gastrointestinal symptoms, other associated diseases, severity of liver histology, or distribution of viral hepatitis markers. There was a significantly higher frequency of positive serum autoantibodies (antinuclear, antimitochondrial, antismooth muscle, and anti-liver-kidney microsomal antibodies) in anti-tTG+/EmA- patients than in the other subjects (9/13 v 10/83; p<0.003). Also, a correlation was found between serum gamma globulin and anti-tTG values (p<0.01). When sera were tested with the ELISA based on human tTG as the antigen, no false positive results were observed: only the two EmA+ patients with atrophy of the intestinal mucosa were positive for anti-tTG while all others were negative, including those false positive in the ELISA based on guinea pig tTG as the antigen. CONCLUSIONS: In patients with elevated transaminases and chronic liver disease there was a high frequency of false positive anti-tTG results using the ELISA based on tTG from guinea pig as the antigen. Indeed, the presence of anti-tTG did not correlate with the presence of EmA or CD. These false positives depend on the presence of hepatic proteins in the commercial tTG obtained from guinea pig liver and disappear when human tTG is used as the antigen in the ELISA system. We suggest that the commonly used tTG ELISA based on guinea pig antigen should not be used as a screening tool for CD in patients with chronic liver disease.

[Retroperitoneal hematoma during heparin therapy. Comments on 3 cases]. / Ematoma retroperitoneale in corso di terapia eparinica. Considerazioni su tre casi.

The authors review the literature during the past ten years relating to the onset of retroperitoneal hemorrhage during heparin treatment. The phenomenon may be attributed to a thrombotic genesis involving the adrenal glands and may or may not be correlated to the presence of heparin-induced immune phenomena. The severity of the phenomenon is readily understood: given that the pathology is heparin-dependent, suspension of heparin treatment is the first main step to be taken; this is evidently a cause of risk in relation to the pathology that imposes the use of heparin. The rarity of this complication means that, according to the authors, it has been undervalued. They report three cases which were brought to their attention over the past three years. On the basis of their experience, the authors underline the importance of knowing the causes that are supposed to be responsible for the complication and the study of blood coagulative status. In order not to overlook the possible adrenal genesis of the phenomenon they also recommend a careful exploration of the adrenal glands when faced with a retroperitoneal hematoma in which the source of hemorrhage cannot be identified.

Del(4)(pter-->q33:) case report and review of the literature.

We report a case on a female newborn child with a deletion of the 4q33qter region. The patient showed facial dysmorphisms, cleft palate and congenital cardiac defect. In order to contribute to a better definition of the 4q33qter deletion syndrome we have compared the clinical findings of our patient with those in nine reported cases. The characteristic symptoms of these patients seem to be: mental retardation, upper slanting of the palpebral fissures, depressed nasal bridge, low set/dysplastic ears, cleft palate, micrognathia, dysmorphic hands and feet.

2q35qter duplication syndrome: phenotypic definition.

Two sibs with multiple congenital anomalies and severe mental retardation were found to have a 2q35qter duplication as a result of a balanced maternal translocation. The clinical features of our two cases are compared with those reported in literature as having either a 2q35qter duplication or a wider duplicated segment without the involvement of any other chromosome deletion or duplication. The typical phenotype is described considering the characteristic clinical features as: hypotonia, hypertelorism, short and beaked nose, flat nasal bridge, thin upper lip, micrognathia, low set and dysmorphic ears, clinodactyly finger V and cryptorchidism.

Involvement of the 4q21 region in human malignant melanomas: cytogenetic and immunocytochemical characterization of three primary cell cultures.

The GRO1 oncogene (melanoma growth-stimulating activity alpha) has been localized in region 4q21. The involvement of this chromosomal region in clonal aberrations found in primary melanoma cell cultures could have an important role in the etiology and pathogenesis of this tumor. We characterized three primary cell cultures obtained from different patients, each of which showed clonal chromosomal aberrations involving the 4q21 region.

Inv dup(15): contribution to the clinical definition of phenotype.

One of the primary goals in medical genetics is a precise clinical definition of chromosomal diseases. This is now possible because of the increased number of case reports and new techniques. A male patient, without a clear-cut syndrome, was cytogenetically investigated. Chromosomal analysis showed a small unidentified bisatellited supernumerary marker. In situ hybridization with a biotin-labeled DNA probe for the chromosome 15 centromere (D15Z1) demonstrated that the marker was derived from chromosome 15. Hybridization with the Prader-Willi Syndrome Cosmid biotinylated probe (localized to band 15q11-q13) showed a signal on both ends suggesting a marker with a symmetrical inv dup(15) and a breakpoint localized in q13. It was then possible to define the karyotype as: 47,XY,+ inv dup(15) (pter-q13::q13-pter). All cases of inv dup(15) reported in the literature were reviewed, paying particular attention to the different breakpoints involved, in order to provide a better clinical definition of this syndrome.

Granulomatous slack skin: cytogenetic and molecular analyses.

Granulomatous slack skin (GSS) is a rare disorder which is considered a slowly evolving T-cell lymphoma associated with granulomatous inflammation that mediates clastolysis. A combined cytogenetic, molecular, and cellular analysis was conducted on a clinically and histologically defined case of GSS. Cell cultures obtained from the skin biopsy showed trisomy of chromosome 8, and the DNA sample extracted from the skin biopsy showed a T-cell receptor beta-chain rearrangement.

First case of deletion 14q11.2q13: clinical phenotype.

The first case of interstitial deletion 14q11.2q13 is related. The patient showed a severe neurological picture, microcephaly, right plagiocephaly, bilateral cryptorchidy, left hip subluxation and various dysmorphisms. The authors analyzed the characteristic symptoms in order to obtain the specific clinical phenotype. In addition they programmed a clinical follow-up to evaluate the life expectation and the evolution of the disease.

20 p duplication as a result of parental translocation: familial case report and a contribution to the clinical delineation of the syndrome.

We report two related patients, presenting duplication 20p, with a characteristic phenotype including normal growth pattern, mental and psychomotor retardation, reduced motor coordination, poor language development, round face and prominent cheeks, vertebral and dental anomalies, and renal malformations. Familial chromosome analysis showed a balanced translocation t(20;21)(p11;q22) in three members of the family. These cases, together with those previously reported in the literature, allow us to make a better delineation of the duplication 20p syndrome, identifying more clearly the symptoms that must be considered as characteristic of this clinical picture.

A balanced complex chromosomal rearrangement (BCCR) with phenotypic effect.

The authors report on a case of balanced complex chromosomal rearrangement (BCCR) with phenotypic effect, describe the dysmorphisms and malformations observed, and discuss the various pathogenetic mechanisms. On the basis of these considerations, they underline the need for careful reporting of examined cases, distinguishing the characteristic signs from dysmorphisms that are described in several other chromosomal aberrations as well. Finally, they stress the importance of a more precise description of BCCRs for the purpose, among others, of a correct formulation of reproductive risk.