Y-chromosome markers in Turner syndrome: Screening of 130 patients.

BACKGROUND: The presence of Y-chromosome material in patients with Turner syndrome (TS) is a risk factor for the development of gonadoblastoma. Cytogenetic analysis detects Y-chromosome mosaicism in about 5% of Turner patients. However, if Y-chromosome sequences are present in only a few cells, they may be missed by routine analysis. The use of molecular techniques to detect the presence of Y-chromosome fragments in such patients is becoming increasingly important. AIM: The objective of our study was to analyze cryptic Y-chromosome derivatives in Hungarian TS patient population by real-time PCR (RT-PCR). SUBJECTS AND METHODS: Cytogenetic and RT-PCR methods were used to examine peripheral blood DNA of 130 Hungarian patients with TS for the presence of Y-chromosome. With RT-PCR, 4 regions throughout the Y-chromosome were analyzed. RESULTS: Initial cytogenetic karyotyping assessing 10-50 metaphases revealed 3 patients with Y-chromosome positivity. RT-PCR revealed further 6 patients with Y-chromosome, who were initially considered as Y-negatives by standard kayotyping. The consecutive cytogenetic analysis of a large number (about 100) of metaphases (in 5 patients) and/or FISH (in 6 patients) however, also confirmed the presence of the Y-chromosome in these patients. Prophylactic gonadectomy was carried out in all 9 patients and 1 of them was diagnosed as having bilateral gonadoblastoma without clinical symptoms. CONCLUSIONS: We recommend a routine molecular screening for hidden Y-chromosome sequences in Turner patients, who are negative for Y-chromosome by conventional cytogenetic analysis, in order to calculate the future risk of developing gonadoblastoma.

Appropriate sampling times for growth hormone (GH) measurement during insulin tolerance testing (ITT) in children.

BACKGROUND: The Pfizer International Metabolic Database (KIMS), a large pharmacoepidemiologic database for adults with growth hormone deficiency (GHD), was recently analyzed to determine which tests are in use to assess GHD and how well they correlate. At the time of this analysis, a total of 15,724 tests had been reported to KIMS. The most frequently used is the insulin tolerance test (ITT), followed in order by the arginine stimulation test (AST), the glucagon stimulation test (GST) and the GH-releasing hormone+arginine (GHRH+arg) test. The ITT correlated with both the AST and the GST, but not with the GHRH+arg. CONCLUSIONS: For the AST and GST, use of a diagnostic threshold of 3 mug/l does not attenuate the effects of severe GHD.

Influence of formulas with borage oil or borage oil plus fish oil on the arachidonic acid status in premature infants.

Several studies have reported that feeding gamma-linolenic acid (GLA) has resulted in no increase in arachidonic acid (AA) in newborns. This result was ascribed to the eicosapentaenoic acid (EPA)-rich fish oil used in these formulas. Docosahexaenoic acid (DHA) sources with only minor amounts of EPA are now available, thus the addition of GLA to infant formulas might be considered an alternative to AA supplementation. Sixty-six premature infants were randomized to feeding one of four formulas [ST: no GLA, no long-chain polyunsaturated fatty acids; BO: 0.6% GLA (borage oil); BO + FOLOW: 0.6% GLA, 0.3% DHA, 0.06% EPA; BO + FOHIGH: 0.6% GLA, 0.3% DHA, 0.2% EPA] or human milk (HM, nonrandomized) for 4 wk. Anthropometric measures and blood samples were obtained at study entry and after 14 and 28 d. There were no significant differences between groups in anthropometric measures, tocopherol, and retinol status at any of the studied time points. The AA content of plasma phospholipids was similar between groups at study start and decreased significantly until day 28 in all formulafed groups, but not in the breast-fed infants [ST: 6.6 +/- 0.2%, BO: 6.9 +/- 0.3%, BO + FOLOW: 6.9 +/- 0.4%, BO + FOHIGH: 6.7 +/- 0.2%, HM: 8.6 +/- 0.5%, where values are reported as mean +/- standard error; all formulas significantly different (P< 0.05) from HM]. There was no significant influence of GLA or fish oil addition to the diet. GLA had only a very limited effect on AA status which was too small to obtain satisfactory concentrations (concentrations similar to breast-fed babies) under the circumstances tested. The effect of GLA on AA is independent of the EPA and DHA content in the diet within the dose ranges studied.

Prenatal diagnosis of steroid 21-hydroxylase deficiency by allele-specific amplification.

OBJECTIVE: Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency (21-OHD) is the most common cause of ambiguous genitalia in females at birth. Here, we report the first prenatal diagnosis of 21-OHD by DNA analysis in Hungary. METHODS: Allele-specific amplification (ASA) of the DNA obtained by chorionic villus sampling was performed. RESULTS: The fetus had a homozygous nonsense mutation (Gln318Stop), suggesting a salt-wasting phenotype. Dexamethasone treatment of the mother was started on the 8th gestational week and, as the fetus was an affected female, it was continued until term. The newborn had normal external genitalia at birth, and severe salt-wasting crisis and postnatal virilization was prevented by mineralo- and glucocorticoid replacement therapy. CONCLUSION: 21-OHD was genotyped by ASA, and virilization of the fetus was prevented by antenatal dexamethasone therapy.

Transient but not permanent neonatal diabetes mellitus is associated with paternal uniparental isodisomy of chromosome 6.

OBJECTIVES: The factors determining the pathogenesis of transient and permanent neonatal diabetes mellitus are poorly characterized. The purpose of this study was to examine the role of chromosome 6 in the pathogenesis of neonatal diabetes mellitus and to detect differences between these 2 phenotypes. METHODS: Microsatellite markers (D6S334, D6S286, D6S310, D6S308, D6S292, D6S311, and D6S403) and human leukocyte antigen DQ alleles were examined using polymerase chain reaction and DNA fragment electrophoresis in 3 patients with transient and 3 patients with permanent neonatal diabetes mellitus. Humoral markers of islet cell autoimmunity and clinical characteristics were analyzed in the 2 groups. RESULTS: A patient with transient neonatal diabetes mellitus (TND) and macroglossia carrying paternal uniparental isodisomy (UPD) of chromosome 6 has been identified. The isodisomy affected the whole chromosome; no maternal chromosome 6 sequences were detected. The permanent neonatal diabetes mellitus cases and the other 2 cases with TND did not have UPD. None of the patients had high-risk type 1 diabetes human leukocyte antigen DQ alleles and most infants were negative for islet cell-specific autoantibodies indicating that none of the 2 forms of neonatal diabetes mellitus is likely to be of autoimmune origin. An association of TND and persistent granulocytopenia is described for the first time. CONCLUSIONS: We propose that transient and permanent forms of neonatal diabetes mellitus have different genetic background and represent different disease entities. TND is associated with UPD of chromosome 6 suggesting that an imprinted gene on chromosome 6 is responsible for this phenotype. It seems that 2 copies of the paternal allele are necessary for the development of TND; therefore, it is likely that overexpression of a putative gene located on chromosome 6 alters pancreatic beta-cell maturation and insulin secretion.

[Acute metabolic cataract as a first manifestation of IDDM in an adolescent girl]. / Akut metabolikus cataracta, mint az 1-es típusú diabetes elsö tünete serdülókorú lányban.

The authors present a case report of a 13.5 yrs old girl. The first manifestation of her diabetes was the sudden decrease of her vision due to bilateral cataract. There was no report of perinatal of actual infection, previous trauma, radiation exposure or drug consumption. She was hypermetropic, for that she regularly underwent ophthalmological examination, including fundoscopy. In the patient's history the usual presenting signs of diabetes i.e. weight loss, polyuria, polydipsia, weakness were absent. Upon admission in the hospital, blood sugar was 32.3 mmol/l, HbAIC 12.3%. After correction of her mild ketoacidosis and controlling her elevated serum glucose level she undervent bilateral cataract phacoemulsification, and artificial lens implant on day 14th and 58th. The patient regained her previous visual acuity, while her diabetes was controlled with 0.83 IU/kg/day of insulin. In the Hungarian literature the authors did not find any similar case. In the literature 22 similar cases were described.

[Androgen-producing adrenocortical adenoma in childhood. Pitfalls of differential diagnosis]. / Androgént termeló mellékvesekéreg adenoma gyermekkorban. A differenciáldiagnosztika buktatói.

A two-year-old girl presented with clitoromegaly and an abdominal mass. Diagnostic procedures including sonography, computerized tomography, scintigraphy and measurement of catecholamines in urine excluded neuroblastoma, but suspected Wilms-tumor. Before completing the steroid measurements therapy was initiated according to Wilms-tumor (preoperative cytostatic therapy followed by surgical removal of the tumor). Morphology of the tumor, the serum and urinary steroid profile proved a benign adrenocortical adenoma producing mainly delta 5-steroids including the weak androgen, dehydroepiandrosterone.