10 research outputs found
Diabetes Mellitus in Adolescents
Dijabetes melitus je skupina metaboliÄkih poremeÄaja karakteriziranih poviÅ”enom koncentracijom glukoze u krvi kao posljedicom nedostatnog luÄenja inzulina, izostanka njegova djelovanja ili kombinacije tih dvaju mehanizama. NajÄeÅ”Äi oblik dijabetesa u djece i adolescenata je dijabetes mellitus tipa 1, no s pandemijom pretilosti svjedoÄimo sve veÄoj uÄestalosti dijabetesa melitusa tipa 2 veÄ u toj dobi. UspjeÅ”no lijeÄenje dijabetesa posebno je važno upravo u vrijeme puberteta, ponajprije kako bi se omoguÄio normalan rast i razvoj te odgodila pojava kroniÄnih mikrovaskularnih komplikacija bolesti. Na žalost, s poÄetkom puberteta glikemijska se kontrola obiÄno pogorÅ”ava. PogorÅ”anje kontrole bolesti pripisuje se ponajprije psiholoÅ”kim problemima adolescentne dobi te slaboj suradljivosti u provoÄenju dijetetskih mjera i primjeni inzulina. Ipak, dokazano je da to nije jedini uzrok te da promjene endokrinog sustava uvelike pridonose pogorÅ”anju kontrole glikemije u adolescenata.Diabetes mellitus is a group of metabolic diseases characterized by high blood glucose levels resulting from defects in insulin secretion, insulin action, or both. The most common form of diabetes in children and adolescents is type 1 diabetes mellitus. However, there is a growing incidence of type 2 diabetes mellitus even in this age group due to a pandemic spread of obesity. Successful treatment of type 1 diabetes is of particular importance during puberty, primarily to achieve normal growth and sexual maturation as well as to reduce the risk of long-term microvascular complications. Yet, with the onset of puberty, glycemic control usually deteriorates. This deterioration is often attributed to the psychological problems of adolescence and poor compliance with diet and insulin administration. However, this is not the complete explanation since endocrine changes of puberty may also contribute to the poor glycemic control in adolescents
Occlusal Molar Surfaces in Females with Turnerās Syndrome
The aim of this study was to identify the molar occlusal features in 73 subjects with
the Turnerās syndrome (TS) and compared to a control group (CG) of 322 healthy females.
The occlusal features were scored on dental plaster casts using the Scoring Procedures
for Key Morphological Traits of the Permanent Dentition: The Arizona State
University Dental Anthropology System (ASU). The results were analyzed through frequency,
percentage and
2-test. TS subjects have more frequent reduction of cusp number,
distolingual cusp on the upper molars and distal cusp on the lower molar, with the
consequent reduction of the occlusal surface. Reduced size of occlusal surface and number
cusps on upper molars resulted in the transformation of rhomboid occlusal shape
into triangular, with the consequent loss of H-shaped groove system (in the upper right
first molars H-shaped groove system was significantly less frequently found in TS (p<
0.05); in the upper left second molars H-shaped groove system was significantly less frequently
found in TS (p<0.01). The X-chromosome aneuploidy can cause a decrease in
developmental homeostasis, which results in the alteration of apposition of the enamel
and in consequently substantial changes of the molar occlusal morphological features
Occlusal Molar Surfaces in Females with Turnerās Syndrome
The aim of this study was to identify the molar occlusal features in 73 subjects with
the Turnerās syndrome (TS) and compared to a control group (CG) of 322 healthy females.
The occlusal features were scored on dental plaster casts using the Scoring Procedures
for Key Morphological Traits of the Permanent Dentition: The Arizona State
University Dental Anthropology System (ASU). The results were analyzed through frequency,
percentage and
2-test. TS subjects have more frequent reduction of cusp number,
distolingual cusp on the upper molars and distal cusp on the lower molar, with the
consequent reduction of the occlusal surface. Reduced size of occlusal surface and number
cusps on upper molars resulted in the transformation of rhomboid occlusal shape
into triangular, with the consequent loss of H-shaped groove system (in the upper right
first molars H-shaped groove system was significantly less frequently found in TS (p<
0.05); in the upper left second molars H-shaped groove system was significantly less frequently
found in TS (p<0.01). The X-chromosome aneuploidy can cause a decrease in
developmental homeostasis, which results in the alteration of apposition of the enamel
and in consequently substantial changes of the molar occlusal morphological features
Primary hypothyroidism and nipple hypoplasia in a girl with Wolcott-Rallison syndrome
Abstract Wolcott-Rallison syndrome (WRS), caused by mutation in the EIF2AK3 gene encoding the PERK enzyme, is the most common cause of permanent neonatal diabetes mellitus (PNDM) in consanguineous families and isolated populations. Besides PNDM, it also includes skeletal abnormalities, liver and renal dysfunction, and other inconsistently present features. We present two siblings, who are WRS patients, and are Albanians from Kosovo born to unrelated parents. The older sister presented with PNDM, exocrine pancreatic insufficiency, short stature, microcephaly, normocytic anemia, delay in speech development, skeletal abnormalities, primary hypothyroidism, and hypoplastic nipples. Sequencing of the EIF2AK3 gene identified a homozygous mutation R902X in exon 13. The younger brother was diagnosed with PNDM and died from hepatic failure suggesting that he has been suffering from WRS as well. Including one previously reported patient from Kosovo carrying the same homozygous mutation, there are three WRS patients from this very small, ethnically homogenous region suggesting founder effect in this population. Conclusion: We postulate that thyroid hypoplasia with primary subclinical hypothyroidism already reported in two WRS patients and nipple hypoplasia could also be the phenotypic reflection of the mutation of pleiotropic EIF2AK3 gene in secretory cells
LOW DOSES OF SULPHONYLURIA AS A SUCCESSFUL REPLACEMENT FOR INSULIN THERAPY IN A PATIENT WITH NEONATAL DIABETES DUE TO A MUTATION OF KCNJ11 GENE ENCODING KIR6.2
Neonatalni dijabetes javlja se u 1 na 300 000 do 400 000 novoroÄenÄadi, a u manje od 50% od njih radi se o trajnom dijabetesu. Nedavno je dokazano da je najÄeÅ”Äi uzrok trajnoga neonatalnog dijabetesa aktivirajuÄa mutacija KCNJ11-gena koji kodira Kir6.2-podjedinicu kalijeva kanala (KATP-kanal) Äija je funkcija regulirana adenozin trifosfatom (ATP). Ovo je otkriÄe važno ne samo kao dokaz monogenske etiologije bolesti veÄ je izmijenilo i naÄin lijeÄenja ovih bolesnika, s obzirom na to da se na mutirane KATP-kanale koji nisu osjetljivi na ATP zbog mutacije Kir6.2-podjedinice i dalje mogu vezati preparati sulfonilureje i potaknuti endogeno izluÄivanje inzulina. Prikazujemo djeÄaka u kojeg su se simptomi dijabetesa javili u dobi od nepuna 3 mjeseca kada je uvedena inzulinska terapija, a u dobi od 4 godine i 7 mjeseci dokazano je da je njegova bolest uzrokovana aktivirajuÄom mutacijom R201H KCNJ11-gena koji kodira Kir6.2-podjedinicu KATP-kanala. Inzulinska terapija uspjeÅ”no mu je zamijenjena vrlo niskim peroralnim dozama glibenklamida, dugodjelujuÄeg preparata sulfonilureje. Ova nova saznanja nameÄu potrebu da se u sve djece u koje se dijabetes javi prije Å”estog mjeseca života Å”to ranije definira genski poremeÄaj, bez obzira na aktualnu životnu dob, a sve informacije o provoÄenju testiranja na mutacije KATP-kanala moguÄe je dobiti na internetskoj stranici www.diabetesgenes.org.Neonatal diabetes mellitus is a rare metabolic disorder with an estimated incidence of 1:300.000 to 400.000 newborns, and less than 50% of the neonates have permanent neonatal diabetes mellitus (PNDM). Recently, activating mutation in the KCNJ11 gene encoding Kir6.2 subunit of the adenosin triphosphate-sensitive potassium (KATP) channel has been described as the most frequent cause of PNDM. Under physiological circumstances KATP channel closure plays a central role in glucose-stimulated insulin secretion from pancreatic beta cells. Sulphonylurea drugs stimulate insulin secretion by binding to and closing KATP channels and thus bypassing beta cell metabolism stimulate the same chain of reactions as glucose. We describe a boy diagnosed with PNDM at the age of 3 months when insulin therapy was started, and at the age of 4.5 years KCNJ11 gene was sequenced and found that the boy carried a de novo activating R201H mutation. Insulin therapy was successfully switched to low doses of oral glibenclamide. Accordingly, it is important to emphasize that every person diagnosed with diabetes before six months of life, however old they actually are, should be tested for KATP mutations which is offered via the website www.diabetesgenes.org
LOW DOSES OF SULPHONYLURIA AS A SUCCESSFUL REPLACEMENT FOR INSULIN THERAPY IN A PATIENT WITH NEONATAL DIABETES DUE TO A MUTATION OF KCNJ11 GENE ENCODING KIR6.2
Neonatalni dijabetes javlja se u 1 na 300 000 do 400 000 novoroÄenÄadi, a u manje od 50% od njih radi se o trajnom dijabetesu. Nedavno je dokazano da je najÄeÅ”Äi uzrok trajnoga neonatalnog dijabetesa aktivirajuÄa mutacija KCNJ11-gena koji kodira Kir6.2-podjedinicu kalijeva kanala (KATP-kanal) Äija je funkcija regulirana adenozin trifosfatom (ATP). Ovo je otkriÄe važno ne samo kao dokaz monogenske etiologije bolesti veÄ je izmijenilo i naÄin lijeÄenja ovih bolesnika, s obzirom na to da se na mutirane KATP-kanale koji nisu osjetljivi na ATP zbog mutacije Kir6.2-podjedinice i dalje mogu vezati preparati sulfonilureje i potaknuti endogeno izluÄivanje inzulina. Prikazujemo djeÄaka u kojeg su se simptomi dijabetesa javili u dobi od nepuna 3 mjeseca kada je uvedena inzulinska terapija, a u dobi od 4 godine i 7 mjeseci dokazano je da je njegova bolest uzrokovana aktivirajuÄom mutacijom R201H KCNJ11-gena koji kodira Kir6.2-podjedinicu KATP-kanala. Inzulinska terapija uspjeÅ”no mu je zamijenjena vrlo niskim peroralnim dozama glibenklamida, dugodjelujuÄeg preparata sulfonilureje. Ova nova saznanja nameÄu potrebu da se u sve djece u koje se dijabetes javi prije Å”estog mjeseca života Å”to ranije definira genski poremeÄaj, bez obzira na aktualnu životnu dob, a sve informacije o provoÄenju testiranja na mutacije KATP-kanala moguÄe je dobiti na internetskoj stranici www.diabetesgenes.org.Neonatal diabetes mellitus is a rare metabolic disorder with an estimated incidence of 1:300.000 to 400.000 newborns, and less than 50% of the neonates have permanent neonatal diabetes mellitus (PNDM). Recently, activating mutation in the KCNJ11 gene encoding Kir6.2 subunit of the adenosin triphosphate-sensitive potassium (KATP) channel has been described as the most frequent cause of PNDM. Under physiological circumstances KATP channel closure plays a central role in glucose-stimulated insulin secretion from pancreatic beta cells. Sulphonylurea drugs stimulate insulin secretion by binding to and closing KATP channels and thus bypassing beta cell metabolism stimulate the same chain of reactions as glucose. We describe a boy diagnosed with PNDM at the age of 3 months when insulin therapy was started, and at the age of 4.5 years KCNJ11 gene was sequenced and found that the boy carried a de novo activating R201H mutation. Insulin therapy was successfully switched to low doses of oral glibenclamide. Accordingly, it is important to emphasize that every person diagnosed with diabetes before six months of life, however old they actually are, should be tested for KATP mutations which is offered via the website www.diabetesgenes.org
Growth hormone positive effects on craniofacial complex in Turner syndrome
Objective: Turner syndrome occurs in phenotypic females with complete or partial absence of X chromosome. The leading symptom is short stature, while numerous but mild stigmata manifest in the craniofacial region. These patients are commonly treated with growth hormone to improve their final height. The aim of this study was to assess the influence of long-term growth hormone therapy on craniofacial morphology in Turner syndrome patients. Design: In this cross-sectional study cephalometric analysis was performed on 13 lateral cephalograms of patients with 45,X karyotype and the average age of 17.3 years, who have received growth hormone for at least two years. The control group consisted of 13 Turner syndrome patients naive to growth hormone treatment, matched to study group by age and karyotype. Sixteen linear and angular measurements were obtained from standard lateral cephalograms. Standard deviation scores were calculated in order to evaluate influence of growth hormone therapy on craniofacial components. Results: In Turner syndrome patients treated with growth hormone most of linear measurements were significantly larger compared to untreated patients. Growth hormone therapy mainly influenced posterior face height, mandibular ramus height, total mandibular length, anterior face height and maxillary length. While the increase in linear measurements was evident, angular measurements and facial height ratio did not show statistically significant difference. Acromegalic features were not found. Conclusions: Long-term growth hormone therapy has positive influence on craniofacial development in Turner syndrome patients, with the greatest impact on posterior facial height and mandibular ramus. However, it could not compensate X chromosome deficiency and normalize craniofacial features
Incidence of Type 1 Diabetes Mellitus in 0 to 14-yr-old Children in Croatia ā 2004 to 2012 Study
BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) among children and adolescents increased during the last 50 yr. The T1DM incidence in Croatia was 8.87/100.000/yr over 1995-2003, with an annual increase of 9%, which placed Croatia among countries with moderate risk for T1DM.
AIM: To investigate incidence rates and trends of T1DM from 2004 to 2012 in 0 to 14-yr-old Croatian children, and to compare the results with previous studies in Croatia and other European countries.
METHODS: T1DM crude incidence rates are estimated for the entire group and three subgroups: 0-4, 5-9, and 10-14 yr. Standardized incidence is calculated using the method of direct standardization according to World Health Organization (WHO) standard world population. The incidence rates by gender, age groups, seasonality, and calendar year, and their interactions were analyzed using Poisson regression model.
RESULTS: A total of 1066 cases were ascertained over 2004-2012. The standardized incidence was 17.23/100.000/yr (95% CI: 16.19-18.26), with no significant differences in incidence rates or trends between boys and girls. Statistically significant annual increase of 5.87% (pā<ā0.001) was found for the whole group, and for the subgroups 5-9 yr (6.82%; pā<ā0.001) and 10-14 yr (7.47%; pā<ā0.001). In the youngest subgroup (0-4 yr), annual increase was lower (2.43%; pā=ā0338) and not statistically significant.
CONCLUSION: The incidence of childhood T1DM is increasing in Croatia, thus placing Croatia among countries with high risk for T1DM. The annual increment of 5.87% is considerably lower than 9.0% reported earlier, but still higher than the European average (3.9%). The increase in incidence ceased in youngest children
Pathogenic variants in GPC4 cause Kelpert Syndrome
Glypicans are a family of cell-surface heparan sulfate proteoglycans that regulate growth-factor signaling during development and are thought to play a role in the regulation of morphogenesis. Whole-exome sequencing of the Australian family that defined Keipert syndrome (nasodigitoacoustic syndrome) identified a hemizygous truncating variant in the gene encoding glypican 4 (GPC4). This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites. We subsequently identified seven affected males from five additional kindreds with novel and predicted pathogenic variants in GPC4. Segregation analysis and X-inactivation studies in carrier females provided supportive evidence that the GPC4 variants caused the condition. Furthermore, functional studies of recombinant protein suggested that the truncated proteins p.Gln506ā and p.Glu496ā were less stable than the wild type. Clinical features of Keipert syndrome included a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and digital abnormalities, whereas cognitive impairment and deafness were variable features. Studies of Gpc4 knockout mice showed evidence of the two primary features of Keipert syndrome: craniofacial abnormalities and digital abnormalities. Phylogenetic analysis demonstrated that GPC4 is most closely related to GPC6, which is associated with a bone dysplasia that has a phenotypic overlap with Keipert syndrome. Overall, we have shown that pathogenic variants in GPC4 cause a loss of function that results in Keipert syndrome, making GPC4 the third human glypican to be linked to a genetic syndrome