Mutation spectrum of type I glycogen storage disease in Hungary.

We performed mutation analysis in 12 Hungarian type I glycogen storage disease (GSD I) patients in order to determine the mutation spectrum. All patients were clinically classified as GSD Ia. Nine patients carried biallelic G6PC mutations (p.Q27fsX35, p.D38V, p.W70X, p.K76N, p.W77R, p.R83C, p.E110Q, p.G222R), with E110Q reported only in Hungary. However, three patients displayed two common G6PT1 (SLC37A4) mutations (p.L348fsX400, p.C183R) which were originally described in association with GSD Inon-a. Review of the literature and our data show that G6PT1 mutations are not associated with neutropenia and related clinical findings in approximately 10% of these cases. Homozygosity for the truncating G6PT1 mutation p.L348fsX400 can be observed with and without neutropenia, indicating that one or more modifiers of the action of G6PT1 exist. Our data are suitable to provide DNA-based and thus noninvasive confirmation of diagnosis in Hungarian patients with this disorder.

Cavernous transformation of the portal vein causing jaundice, presenting in the form of Wilson's disease.

The following is a case review of portal vein cavernous malformation presenting with intermittent cholestasis and jaundice in a 4 year old child. Correct assessment was supported by radiology, later laparoscopy, yet hindered by histopathology representative Wilson's disease and elevated urinary copper excretion. During surgical procedure the stenosis of the common bile duct secondary to extremely dilated portal vein reticulation was solved by Roux-en-Y choledochojejunostomy. After a one-year follow up the child remains asymptomatic.

Prevalence of alpha1-antitrypsin phenotypes in patients with IgA nephropathy.

BACKGROUND: alpha1-antitrypsin (AAT) is the main protease inhibitor in the blood. Several different AAT phenotypes exist. The most common variant is the MM phenotype, which is also associated with normal AAT levels. The less common phenotypes with Z and S variants are associated with low AAT levels. AAT deficiency is a risk factor for pulmonary emphysema, liver impairment and some immune-mediated diseases, some of which are also associated with IgA nephropathy (IgAN). In fact, liver impairment resulting from AAT deficiency may directly contribute to renal abnormalities resembling IgAN. PATIENTS AND METHODS: We investigated AAT phenotype and AAT levels in 100 IgAN patients who did not have end-stage liver disease. Fifteen patients in our sample had secondary IgAN. We also tested for the presence of renal deposition of AAT in patients heterozygous for AAT variants as well as in a randomly chosen group of patients with MM phenotype. We checked for any association between AAT phenotype and the progression of IgAN as well as the prevalence of diseases associated with IgAN (i.e. secondary IgAN). RESULTS: Twelve patients in our sample were heterozygous for AAT variants. Phenotypes were MZ in 5 patients, MS in 3, MF in 1, ML in 2 and ME in 1 patient. AAT levels were lower in these 12 patients than in those homozygous for the M variant (1.17+/-0.46 vs. 1.44+/-0.34 g/l, p < 0.05). We found renal deposition of AAT in 2 heterozygous patients and in 1 of the 12 patients which were randomly chosen. End-stage renal (ESRF) failure developed in 3 of the 12 heterozygous patients and in 6 of the 88 homozygous patients (p = 0.07) during the follow-up. The prevalence of heterozygosity was significantly higher in patients with secondary IgAN than in those with primary IgAN ((5/15 vs. 7/85; p < 0.02). CONCLUSIONS: AAT phenotype is not associated with the risk of primary IgA nephropathy, but might have an impact on disease outcome as well as on the risk of secondary IgAN.

Short-term omeprazole treatment does not influence biochemical parameters of bone turnover in children.

Gastric proton pump inhibitors are widely used in the treatment of dyspeptic problems and for the eradication of H. pylori infection. Data are not available on whether omeprazole, a representative of proton pump inhibitors, influences the function of osteoclastic H+-pump in children. We studied the impact of short-term omeprazole administration on the biochemical parameters of bone turnover in pediatric patients. Urinary calcium excretion, serum total alkaline phosphatase activity, collagen type 1 crosslinked C-telopeptide, and osteocalcin levels were determined in 34 children [20 girls (9 prepubertal) and 14 boys (6 prepubertal)] before and after 2 weeks of omeprazole treatment at a dose of 20 mg/day. The measured parameters were within the healthy reference range in each patient. None of them altered during the study in any age or in any gender. We conclude that omeprazole, at a dose of 20 mg/day, does not significantly influence the investigated biochemical parameters of osteoclast and osteoblast function in pediatric patients.

[Treatment of infants with acute diarrhea in Hungary]. / A csecsemókori akut hasmenés kezelésének hazai gyakorlata.

In the treatment of infants with acute diarrhoea complicated by mild to moderate dehydration, there is a great importance of rapid rehydration over 3-4 hours with oral rehydration solution containing 60 mmol/l sodium and then the rapid reintroduction of normal diet or breast feeding which should be continued all the time if possible. The pharmacological treatment of diarrhoea is not justified. In the present study which was part of a European multicentre survey using questionnaires the authors analysed how the recommendation of European Society of Pediatric Gastroenterology, Hepatology and Nutrition are followed in Hungary. It was evaluated 131 returned questionnaires, 80 of primary care and 51 of hospital-based pediatricians. The overwhelming majority of pediatricians (92%) recommended the oral rehydration at the beginning of treatment. The four fifth of them use the ORS with recommended composition. Only 31% of them use rapid oral rehydration over 3-4 hours. Merely 10% of them suggest the early reintroduction of normal feeding after the oral rehydration, while more than half of the respondent pediatricians (52%) think that temporarily the use of lactose free formula is justified. It is a very favourable fact that 84% of doctors recommend the continuation of breast feeding. Some kind of drugs for the treatment of diarrhoea is suggested by 15% of repliers. On the base of results it is obvious that the guidelines for the treatment of acute diarrhoea in infancy is complied only partially in Hungary and the reintroduction of normal feeding is delayed.

[Helicobacter infection in children]. / Gyermekkori Helicobacter pylori-infekció.

Consensus was achieved on the following issues: in children H. pylori infection causes chronic gastritis, but rarely gastric and duodenal ulcer disease. Eradication of H. pylori leads to healing of these conditions. To-date, there is no evidence demonstrating a link between H. pylori gastritis and abdominal pain except in those children where a gastric or duodenal ulcer is present. Children should be investigated for H. pylori infection only if their symptoms are suggestive of organic disease rather than functional abdominal pain. Endoscopy with biopsies is the optimal method to investigate a child with upper gastrointestinal symptoms suggestive of organic disease but this should only be carried out when a diagnostic work up using non-invasive methods has excluded other causes such as lactose maldigestion, constipation, coeliac disease, liver or biliary tact disease. If H. pylori is identified through investigations carried out during endoscopy the infection should be treated. Treatment should be monitored with a reliable non-invasive test and the 13C-urea breath test is the preferred method. H. pylori eradication in such children will cure gastritis but there is no data to support a relationship between a cure of H. pylori gastritis and symptom relief except in patients with ulcer disease. Further studies are needed to establish whether there are any specific symptoms associated with H. pylori gastritis alone and whether infected children without ulcer disease benefit from anti-H. pylori therapy regarding their symptoms. This consensus meeting did not deal with the optimal therapy for H. pylori infection as there are insufficient studies concerned the best treatment in children.

Dipeptidyl peptidase activity of CD26 in serum and urine as a marker of cholestasis: experimental and clinical evidence.

Dipeptidyl peptidase IV (CD26) is a membrane-associated enzyme that is expressed on the surface of T cells and on the hepatocyte brush border. In a soluble form it is present in serum. CD26 has been implicated in the regulation of T cell activation and in the metabolism of hormones and cytokines. Dipeptidyl peptidase (DPP) activity is elevated in the urine and serum of patients with biliary atresia (BA). To clarify the role of cholestasis in the development of increased serum and urinary DPP/CD26 activity, we studied the mechanism of activity increase in experimentally induced cholestasis of CD26-deficient and wild-type rats. The clinical utility of serum and urinary DPP/CD26 activity measurements was tested in adult and pediatric patients with hepatobiliary diseases and in liver transplant recipients. The results establish CD26-associated serum DPP activity as a novel, clinically useful marker of cholestasis and demonstrate that in contrast with alkaline phosphatase levels, DPP levels do not change in metastatic bone disease. Additionally, DPP activity is useful as a urinary test of cholestasis in infants who are not receiving nephrotoxic medication.

Detection of mtDNA deletion in Pearson syndrome by two independent PCR assays from Guthrie card.

Pearson syndrome is a multisystem juvenile condition associated with deletions in the mitochondrial genome. The most common 4977 bp deletion of mitochondrial DNA (mtDNA) can mainly be detected in the patients' peripheral blood. Here we report a child with a clinically unclarified diagnosis where molecular genetic results proved Pearson syndrome from stored dried blood sample 6 months after the patient's death. PCR amplification around the breakpoint of the most common mtDNA deletion could detect the presence of mutated mtDNA. Another polymerase chain reaction (PCR) assay indicated the low level of wild type mtDNA in patients' blood. We believe that this case shows the importance of storing Guthrie card and the availability of detection of Pearson syndrome from dried blood sample.

[Late onset type I tyrosinemia]. / Késöi kezdetü I. típusú tyrosinaemia.

The authors present a case of tyrosinemia type 1, 3 years old girl at the time of diagnosis. The presenting symptoms were 3 times colic, obstipation, acute encephalopathy, hypertension, hyponatremia, according to the porphyric crisis. Her kidney function tests gave normal results during illness, only once an increased calcium turnover was observed. She has no singe of rachitis. Cirrhosis of the liver was proved by biopsy because of progressively rising gammaGT and alfa-fetoprotein levels. A new ensime-blocker (NTBC) treatment was started in an international collaboration. The authors compare the history of this case to that of others published in the literature. They summarize the pathomechanism of the disease.

Two new mutations in the glucose-6-phosphatase gene cause glycogen storage disease in Hungarian patients.

Glycogen storage disease type 1a (von Gierke disease, GSD-1A) is caused by the deficiency of microsomal glucose-6-phosphatase (G6Pase) activity which catalyzes the final common step of glycogenolysis and gluconeogenesis. The cloning of the G6Pase cDNA and characterization of the human G6Pase gene enabled the identification of the mutations causing GSD-1a. This, in turn, allows the development of non-invasive DNA-based diagnosis that provides reliable carrier testing and prenatal diagnosis. Here we report on two new mutations E110Q and D38V causing GSD-1a in two Hungarian patients. The analyses of these mutations by site-directed mutagenesis followed by transient expression assays demonstrated that E110Q retains 17% of G6Pase enzymatic activity while the D38V abolishes the enzymatic activity. The patient with the E110Q has G222R as his other mutation. G222R was also shown to preserve about 4% of the G6Pase enzymatic activity. Nevertheless, the patient presented with the classical severe symptomatology of the GSD-1a.

[Favorable effect of breast feeding and late introduction of cow's milk on the prevention of suspected allergic symptoms in infancy]. / Az anyatejes táplálás és a késöi tehéntejfehérje-bevitel kedvezö hatása a csecsemökori allergiára utaló tünetek megelözésében.

The authors studied in Káposztásmegyer belonging to the IVth district of Budapest the way of feeding and the frequency of skin, respiratory and gastrointestinal symptoms suggesting allergic disease in the first year of life of 405 infants born in 1993. It was analyzed whether the frequency of symptoms was related to the duration of breast feeding and the first introduction of cow's milk protein. In the 53 infants with symptoms the duration of breast feeding was significantly shorter (mean 12.5 weeks) than in the symptomless ones (20.2 weeks, p < 0.01). The first introduction of cow's milk was also significantly earlier in the infants with symptoms (mean 6.2 weeks) than in the healthy ones (11.8 weeks, p < 0.01). Cow's milk protein was more frequently introduced before the age of one months in infants with suspected cow's milk protein allergy (56%), than in the symptomless infants (34%, p < 0.01). It can be concluded that the shorter duration of breast feeding and the earlier exposure of cow's milk protein may increase the prevalence of allergic symptoms in infancy.

[Simultaneous occurrence of ulcerative colitis and psoriasis in childhood]. / Colitis ulcerosa és psoriasis együttes elöfordulása gyermekkorban.

Authors report of a 10 years old girl who at age 2 showed signs of psoriasis and after 8 years typical symptoms of ulcerative colitis manifested. In connection with this case the association of two diseases is emphasized which may be explained by the similarity of genetic and immunological factors in both disorder. It is accentuated that at the observation of enteral symptoms in patients with psoriasis the possibility of non specific inflammatory bowel disease has also to be considered.

[Biliary calculi in infancy and childhood]. / Epekövesség csecsemö- és gyermekkorban.

Authors analyse the data of 48 children with cholelithiasis (29 girls, 19 boys, mean age: 8,7 years). In the infants the gallstones developed mostly on the basis of predisposing disease and in them the spontaneous stone dissolution is frequent. Patients were divided into two groups. In the I. group gallstones developed at the presence of predisposing diseases, in the II. group such disease were not identified. In childhood more patients belong to the I. group as our results and earlier reports show, in this group characteristic symptoms cannot be found. In the II. group the vague abdominal pain was the most frequent symptom. Beyond the age of 10 years the sex ratio and the symptoms are similar to those of adults. In the I. group in 8 cases, while in the II. in 16 cases was operation done. In the latter group in two patient stone dissolution took place with Ursodeoxycholicacid. In childhood complication are infrequent. The ultrasound examination is a very useful tool in the diagnosis and follow up of these patients.

Cardiac vagal hyperactivity in adolescent anorexia nervosa.

Adolescent anorexia nervosa, a psychiatric disease with high mortality, is often associated with bradycardia. We studied the vagal control of sinus node function in anorexic subjects, to investigate the mechanism of anorexic bradycardia. Cardiac vagal tone was determined in a group of 11 adolescent anorexic girls and in 11 age- and height-matched controls. Cardiac vagal tone in the anorexic patients was measured as the change in R-R interval in response to complete cholinergic blockade; in addition, non-invasive indices of cardiac vagal tone and baroreflex sensitivity were determined in both anorexic and control subjects. Cardiac vagal tone in anorexic subjects was 465 +/- 52 (SE) ms, about 30% higher than values reported for healthy subjects. Vagal tone values were directly related to percent weight loss (R = 0.69, P = 0.017). Non-invasive indices of both cardiac vagal activity and baroreflex sensitivity were significantly higher in the anorexic group as compared to controls; the percent increase of cardiac vagal tone, however, exceeded the increase of baroreflex sensitivity. Cardiac vagal hyperactivity significantly contributes to the bradycardia of anorexic subjects. The excess vagal activity is only partly explained by enhanced baroreflex sensitivity.

[Studying the role of Helicobacter pylori infection in recurrent abdominal pain in children]. / Helicobacter pylori fertözés vizsgálata visszatérö hasfájós gyermekeknél.

The authors studied the role of Helicobacter pylori at recurrent abdominal pain in childhood. Helicobacter pylori infection hasn't been found at the 42 examined children. The endoscopy showed esophagitis in 34 cases. The quick urease test, the histological examination, and the bacterial culture are proposed to carry out in ulcus duodeni, gastritis typ. B ulcus ventriculi and not necessary to carry out if the endoscopy shows only esophagitis--emphasize the authors.

[ A case of successfully treated duodenal hemangioma]. / Duodenum haemangioma gyógyult esete.

In some cases the radical removal of gastrointestinal hemangiomas involves an excessive risk or too extensive operation. Consequently some other solution has to be applied. At our patient with duodenum haemangioma the combination of angiographic embolism and endoscopic sclerotization was successfully employed.