Impact of Type 2 diabetes on Glucokinase diabetes (GCK-MODY) phenotype in a Roma (Gypsy) family - case report.

OBJECTIVES: Glucokinase (GCK) diabetes is a mild form of the monogenic diabetes characterized by the fasting hyperglycemia without signs of metabolic syndrome and very low risk for chronic complications of diabetes. For the Type 2 diabetes (T2D), signs of the metabolic syndrome with high risk for chronic micro- and macro-vascular complications are typical. The prevalence of the GCK-diabetes is estimated from 0.5 to 1% in the diabetic patients. The T2D is the most prevalent type of the diabetes (it encompasses more than 85% of all the diabetic patients). According to the epidemiology, the coincidence of these two diabetes subtypes may occur; nevertheless no case reports on the above mentioned two diabetes subtypes have been published. The aim of the study was: 1) to perform the DNA analysis in three brothers, two of them with the fasting hyperglycemia and one with normal glucose tolerance, and their father with T2D metabolic syndrome and 2) to study the coincidence of the GCK-diabetes with T2D and its effect on the diabetic phenotype. PATIENTS AND METHODS: We report about a Roma (Gypsy) family consisting of three brothers: 17 years old probant and two older brothers (21 and 25 years), and their father. The probant is suffering from fasting hyperglycemia. His 25 years old diabetic brother and their father suffer from obesity, hypertension, dyslipidemia, and hyperglycemia. The glucokinase gene was analyzed by direct sequencing in each of the brothers and their father, and appropriate phenotype characteristics were also carried out on each of the family members. RESULTS: In the proband and his diabetic brother with the fasting hyperglycemia, a heterozygous mutation of the glucokinase gene p.Arg36Trp was found. The proband's phenotype was consistent with the GCK-diabetes, while the diabetic brother displayed already features of the metabolic syndrome. Although, the latter one suffered from the overweight, hypertension, and elevated triglycerides, his fasting hyperglycemia (8.3 mmol/l) was still consistent with the GCK-diabetes. Their father is also a heterozygous mutation carrier of the same mutation displaying all the features of the metabolic syndrome. In his case, the fasting hyperinsulinemia (43.5 µU/ml) and fasting plasma glucose (10.4 mmol/l) are more typical for the T2D than GCK-diabetes. CONCLUSIONS: We found coincidence between the GCK-diabetes and T2D in the members of a single Roma (Gypsy) family. Since the chronic complications are rare in the GCK-diabetes, the major risk factor for the further morbidity may be in the development of the T2D. The overlapping of the GCK-diabetes with other types of diabetes, particularly the T2D, makes the diagnostics difficult and therefore, it might be one of the reasons why the estimated prevalence of the GCK-diabetes seems to be higher than the real one as it has been reported in several studies.

[Pendred syndrome among patients with hypothyroidism: genetic diagnosis, phenotypic variability and occurrence of phenocopies]. / Pendreduv syndrom u pacientu s hypotyreózou: genetická diagnostika, fenotypová variabilita a výskyt fenokopií.

BACKGROUND: Pendred syndrome (OMIM274600) is one of the causes of congenital hypothyroidism due to thyroid dyshormonogenesis. It is an autosomal recessive disease classically characterized by dyshormonogenetic goitre and sensorineural deafness. It is caused by mutations in PDS/SLC26A4 gene encoding for pendrin--an anion transporter, mostly expressed in the thyroid gland and the inner ear. The thyroid impairment in Pendred syndrome develops only in 80% of affected individuals in form of a euthyroid or hypothyroid goitre, which is rarely present at birth, when it can be diagnosed by the neonatal screening for congenital hypothyroidism. The study was aimed to identify patients with Pendred syndrome among children with congenital or postnatal non-autoimmune hypothyroidism and subsequently confirm the diagnosis by finding mutations in the PDS/SLC26A4 gene. METHODS AND RESULTS: We examined two-hundred thirty-six Caucasians with hypothyroidism diagnosed by screening or developing later in childhood. The clinical diagnosis of Pendred syndrome was based on the laboratory and ultrasonographic signs of thyroid dyshormonogenesis (elevated TSH, low T4/fT4, goitre or normal thyroid volume) in association with sensorineural hearing loss. In subjects clinically diagnosed as Pendred syndrome, we sequenced all 21 exons of the PDS/SLC26A4 gene and their flanking intron-exon junctions. Among 236 children, nine fulfilled the diagnostic criteria of Pendred syndrome. In four, the diagnosis was confirmed by identification of mutations in the PDS/SLC26A4 gene, the remaining five patients were concluded phenocopies. CONCLUSIONS: Our study confirms the high phenotypic variability of thyroid impairment in Pendred syndrome and underlines the necessity of a molecular-genetic investigation for establishing the diagnosis in regard of the great number of phenocopies. However, from the endocrinologist's point of view, the genetic testing is only reasonable in patients with congenital hypothyroidism due to dyshormonogenesis in association with sever to profound sensorineural hearing loss.

[Hyperinsulinism--a new pathogenic cause of cardiovascular diseases]. / Hyperinzulinizmus--nová patogenetická cesta kardiovaskulárnych chorôb?

Authors call attention to the insulin-resistance and following hyperinsulinism, as important and may be also the basic factor, which is determining for high cardiovascular morbidity and mortality. Authors analyze the pathogenesis of the Reaven's syndrome X, syndrome 5H and their symptoms--insulin-resistance, hyperinsulinism, hyperlipemia with obesity, hypertension and eventually hirsutism. Authors analyze the congenital and acquired factors, which influence its manifestation and so occurrence of the cardiovascular diseases in the adulthood. In the past paediatricians gave little attention to this problem because they supposed the problem as the problem of the adult medicine. We can see that full 5H syndrome is only the top of the iceberg with basis in childhood. In the prevention of the cardiovascular diseases the task of the paediatricians is therefore not substitutable and in future they need to give to the X syndrome extraordinary attention.

[Problems in children with growth hormone deficiency in Slovakia]. / Problematika detí s deficitom rastového hormónu na Slovensku.

The authors give an account of 71 patients treated on account of complete growth hormone deficiency in Slovakia. Before the age of five the diagnosis was established in 24 children, after the age of 10 in 17 patients. Nine patients suffer from panhypopituitarism, while isolated deficiency of growth hormone was recorded in 34 patients. Perinatal pathology plays an important role in the aetiology. A tumour caused the disorder in five children. Treatment of the majority of patients was not systematic and was inadequate because of shortage of growth hormone. When regular substitution treatment was started before the age of 8 years, the therapeutic results were very satisfactory. The authors draw attention to the danger of further deterioration of care of children with growth hormone deficiency for economic reasons.

[Fluorescence angiography in children with type I diabetes mellitus]. / Fluorescencná angiografia u detí s diabetes mellitus I. typu.

The authors present results of research pertaining to chronic ophthalmological complications in a group of 72 children with type I diabetes mellitus. Fluorescent angiography revealed a double incidence of diabetic ophthalmological complications, as compared with ophthalmoscopic examination and at the same time the authors detected a higher incidence of diabetic retinal changes in children during puberty.

Increased incidence of congenital hypothyroidism in Gypsies in east Slovakia as compared with white population.

Ethnic Gypsies represent 9 percent of total population of East Slovakia. However, during first three and half years of compulsory screening of congenital hypothyroidism (CH) there were 15,346 Gypsy newborns which was 16.8 percent of a total number of 90,760 newborns. Out of these Gypsy newborns 7 cases of CH were found (i.e. 1:2192), while 12 cases of CH were observed among 75,414 white newborns (i.e. 1:6284), which was significantly less than that in newborns Gypsies (P less than 0.05). Since the far highest coefficient of inbreeding ever reported for any European population or ethnic groups has been found by others in newborns Gypsies living in Slovakia (Fg = 0.017 obtained by genealogic method and Fi = 0.084 obtained by the method of isonymy), it may be suggested that a high incidence of CH in newborns Gypsies may be due to some genetic and hereditary factors. Though a direct interrelationship cannot be definitely established from the present data and still remains far from to be elucidated, the present observation may be considered as a contribution to the study of this problem.