The authors describe four members of a family with a novel P284S presenilin 1 mutation presenting a clinical phenotype characterized by early-onset dementia, paratetraparesis, dysarthria, dysphagia, and marked involvement of brain white matter. The distinctive clinical and MRI findings in the family studied extend the phenotypic spectrum of dementia associated with mutation of the PS1 gene.

The objective of this study was to study genetic and phenotypic features of a family with X-linked Charcot-Marie-Tooth consisting of a healthy father, affected mother, two affected sons and one healthy one. A detailed electrophysiological and neuroimaging study, along with sequencing of the Cx32 gene, was performed in all family members. A novel Cx32 123 G>C mutation, determining an aminoacid variation (Glu41Asp), was found in the mother and the affected sons. An alteration in brainstem evoked potentials was found in the mother and one affected son. The affected son, who underwent magnetic resonance imaging, showed symmetrical hyperintensities in paratrigonal white matter, not found in his heterozygous mother, while both subjects exhibited alterations in brain metabolite ratios derived from localised proton-magnetic resonance spectroscopy. These data extend previous findings about central nervous system involvement in Cx32 mutated subjects and further support a functional role of the protein expression in oligodendrocytes.

Clinical picture of adult's celiac disease (CD) may be protean, including both organic and functional disturbances such as dyspeptic symptoms that may in part be ascdbed to associated gut dismotility.We studied upper digestive function in 10 consecutive celiac patients (8 F, 2 M; age range 20-64 yr), diagnosed according to Marche's criteria, following a free diet and complaining of dyspepsia.40% had sporadic dysphagia and one als0 had associated scleroderma.Esophageal 24 hour pH-metry, 99Tc Scintigraphic study of gastric emptying of liquid meal, esophageal and gastrointestinal (8 pts) manometric studies, and tests of autonomic function (hearth rate response to deep breathing, cough test, lying-tostanding and Valsalva manoeuvre, according to Ewing's criteria) were performed.Upper gut organic disease, gastric intraepithelial lymphocitic infiltration and Helicobacter pylori gastritis were excluded.Manometric studies were carried out by standard perfused system, and the gastrointestinal ones were conducted for 5 hours during fasting and 1 after feeding.As control group 33 healthy subjects of both sexes (age range 20-35 yr) were recruited.RESULTS: 50% of patients had esophageal motor abnormalities (nutcracker esophagus 20%, nonspecific disorders 20% and scleroderma 10%) and 30% had evidence of pathologic acid reflux.Analysis of gastro-intestinal tracings showed activity fronts (AF) in all subjects, but with a significantly reduced frequence of the antral component (1/8 vs 18/33, p< 0.01); their mean duration was reduced (3,5-,-0.9vs 6.9±1.4 min, p<0.01) and their recurrence was increased (1/195 vs 1/99 min, p<0.01).85% of patients displayed isolated or nonpropagated bursts and/or clusters of contractions (also present in the postprandial period in 3 subjects) and antral postprandial hypomotility.40% of patients showed delayed gastric emptying by scintigraphic study (7/2 > 100 mins) that correlated to manometric picture; 20% of patients had positive autonomic tests (score > 4).We conclude that in untreated CD upper gastrointestinal dismotilities are frequently present, and these may be ascdbed to a visceral neuropathy, although autonomic tests do not show a stdct concordance with the manometric ones.

The Sardinian population in many aspects differs from other Caucasoid populations, particularly for its degree of homogeneity. For this reason we have studied 50 adult Sardinian patients with celiac disease (CD) and 50 control healthy Sardinian individuals by RFLP analysis and by extensive oligotyping for 17 HLA-DPB1, 8-DQB1 and 9-DQA1 alleles, and established their -DPB1 alleles and -DQB1 -DQA1 genotypes. The heterodimer HLA-DQB1*0201/-DQA1*0501, present in 96% of our patients, is strongly associated with CD susceptibility, confirming published reports. On the other hand we found in 11 of 50 probands (22%) the presence of the allele -DQB1*0502/DQA1*0102. This genotype is extremely rare in other Caucasian populations and appears to confer limited protection in CD Sardinian patients.

Coeliac sprue is a relatively frequent disease with protean clinical manifestations. Recent studies suggest that gastrointestinal motor abnormalities may explain some symptoms complained of by such patients. We investigated whether coeliac patients have oesophageal motor abnormalities from both a clinical and a physiological point of view. Thirty-six consecutive adult sprue subjects (14 during the florid phase and 22 on gluten-free diet) were studied. A clinical questionnaire on gastrointestinal symptoms (with emphasis on those of oesophageal origin) was administered. Moreover, 18 patients (13 on free and five on gluten-free diet) gave their consent for oesophageal manometry and eight subjects for pH-metry also. Oesophageal clinical symptoms were compared with those of 144 age- and sex-matched controls from a general population sample, and manometry with that of 34 healthy volunteers. Of coeliac patients 50% complained of dysphagia (P < 0.001 vs. controls) and 14% noncardiac chest pain (P = NS vs. controls). Manometric examination showed motor abnormalities in 67% of the subjects examined, consisting of nutcracker oesophagus, hypotonic lower oesophageal sphincter associated with simultaneous contractions, and frequent repetitive (> 3 peaks) contractions. These abnormalities were equally distributed among free and gluten-free diet patients. pH-metry showed only one pathological reflux out of eight subjects studied. We conclude that patients with coeliac sprue may display abnormal oesophageal motility. This confirms previous studies suggesting that gastrointestinal motor abnormalities should probably be added to the clinical spectrum of the disease.

The Sardinian population in many aspects differs from other Caucasoid populations, particularly for its degree of homogeneity. For this reason we have studied 50 adult Sardinian patients with celiac disease (CD) and 50 control healthy Sardinian individuals by RFLP analysis and by extensive oligotyping for 17 HLA-DPB 1, 8-DQB I and 9-DQA 1 alleles, and established their -DPB I alleles and -DQB I -DQA I genotypes. The heterodimer HLA-DQB 1 *0201/-DQA 1 *0501, present in 96% of our patients, is strongly associated with CD susceptibility, confirming published reports. On the other hand we found in 11 of 50 probands (22%) the presence of the allele -DQB 1 *05021 DQA1*0102. This genotype is extremely rare in other Caucasian populations and appears to confer limited protection in CD Sardinian patients.

The duodenal endoscopic pictures were studied in 12 adult coeliacs patients, aged between 18 and 76 years, mean age 41.9 +/- 17.6 yrs. All patients carried out D-xylose absorption test, antigliadin IgA antibodies and distal duodenum biopsy. The more frequent endoscopic picture was the disappearance of Kerckring's folds; nevertheless in 5 patients the loss of Kerckring's folds was associated with duodenal mucosa irregularity. We believe that in future the knowledge of this new endoscopic picture will be useful in coeliac's disease diagnosis.

The IgA antigliadin antibodies AGA title was detected in 37 patients with IDDM, mean age 32.59 +/- 14.71, where mean duration of disease was 8.76 +/- 9.62 years, and 29 patients with NIDDM, mean age 55.31 +/- 14.71, where disease lasted 11.5 +/- 5.55 years. A group of 51 normal pts. was employed as control. In IDDM group 2 cases on 37 showed high AGA title (case n. 1 and n. 2) but just the case n. 1 where IDDM lasted 16 years, showed an histologic picture of coeliac disease (partial villous atrophy), while in the case n. 2 where IDDM was at the onset, the histologic picture was normal. The increase of AGA title in the IDDM at the onset is rarely associated with coeliac disease, but it seems to be an aspecific response. Viceversa an increased AGA title is in IDDM for greater than 1 years often associated with coeliac disease. In NIDDM no high AGA title was found. The prevalence of coeliac disease in our patients with IDDM was 1:37 and we suggest that diabetics be screened routinely for antigliadin antibody.

Intraluminal manometry was used to assess the motor activity of the oesophagus and upper (UES) and low (LES) oesophageal sphincter in 10 patients, 5 female and 5 male, average age 35.9 range 17-50, suffering from insulin-dependent diabetes mellitus. Non-invasive cardiovascular tests were also performed to evaluate autonomous neuropathy together with control tests of glyco-metabolic compensation (fructosamine and HbA1c). An increase in the basic tone of the UES was observed in 8 patients while in 3 this was associated with its incomplete release. Five patients evidenced aspecific motor disturbance such as spontaneous motor activity characterised by repetitive segmentary waves at times with biphasic appearance. IOS activity was within normal limits. It is considered that these disturbances may be attributable to the autonomous neuropathy that often complicates diabetes mellitus and that oesophageal motor disturbance, albeit aspecific, should be considered an early sign of autonomous neuropathy. It is therefore though that manometric oesophageal study may be considered a useful investigative tool for early evidencing of disturbances linked to autonomous neuropathy.

The authors describe two cases of celiac disease that simulated mesangial IgA nephropathy (Berger's disease). In both cases, gluten-free diet rapidly abated the histological and clinical picture, renal as well as intestinal. The authors conclude that all patients with Berger's disease should be tested systematically for antigliadin antibodies of the IgA class with a view to more accurate clinical classification and therapeutic planning.

The functional alterations in the digestive tract observable during diabetes mellitus are frequent albeit often asymptomatic. They affect several different districts and are still not clearly defined aetiopathogenetically. It was therefore decided to evaluate the gastric transit times of a balanced liquid meal labelled with 99-Tc-colloidal sulphide in a group of patients suffering from insulin-dependent diabetes and in a group of 10 controls. The anatomical integrity of the oesophago-gastro-duodenal tract has been evaluated by endoscopy and histology. Transit times (T/2) proved significantly increased in diabetics (92.38 +/- 33.397 minutes) compared to the controls (48.63 +/- 16.423 minutes), p 0.001. No correlation was observed between gastric transit times, duration of the diabetic disease, degree of glyco-metabolic compensation and presence of autonomous neuropathy.