AIMS/HYPOTHESIS: The aim of this work was to evaluate geographical variability and trends in the prevalence of diabetic ketoacidosis (DKA), between 2006 and 2016, at the diagnosis of childhood-onset type 1 diabetes in 13 countries over three continents. METHODS: An international retrospective study on DKA at diagnosis of diabetes was conducted. Data on age, sex, date of diabetes diagnosis, ethnic minority status and presence of DKA at diabetes onset were obtained from Australia, Austria, Czechia, Denmark, Germany, Italy, Luxembourg, New Zealand, Norway, Slovenia, Sweden, USA and the UK (Wales). Mean prevalence was estimated for the entire period, both overall and by country, adjusted for sex and age group. Temporal trends in annual prevalence of DKA were estimated using logistic regression analysis for each country, before and after adjustment for sex, age group and ethnic minority status. RESULTS: During the study period, new-onset type 1 diabetes was diagnosed in 59,000 children (median age [interquartile range], 9.0 years [5.5-11.7]; male sex, 52.9%). The overall adjusted DKA prevalence was 29.9%, with the lowest prevalence in Sweden and Denmark and the highest in Luxembourg and Italy. The adjusted DKA prevalence significantly increased over time in Australia, Germany and the USA while it decreased in Italy. Preschool children, adolescents and children from ethnic minority groups were at highest risk of DKA at diabetes diagnosis in most countries. A significantly higher risk was also found for females in Denmark, Germany and Slovenia. CONCLUSIONS/INTERPRETATION: DKA prevalence at type 1 diabetes diagnosis varied considerably across countries, albeit it was generally high and showed a slight increase between 2006 and 2016. Increased awareness of symptoms to prevent delay in diagnosis is warranted, especially in preschool children, adolescents and children from ethnic minority groups.

• MeSH
• diabetes mellitus 1. typu epidemiologie   genetika   metabolismus   MeSH
• diabetická ketoacidóza epidemiologie   genetika   metabolismus   MeSH
• dítě MeSH
• lidé MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Dánsko MeSH
• Německo MeSH
• Slovinsko MeSH

Genomics methodologies have significantly improved elucidation of Mendelian disorders. The combination with high-throughput functional-omics technologies potentiates the identification and confirmation of causative genetic variants, especially in singleton families of recessive inheritance. In a cohort of 99 individuals with abnormal Golgi glycosylation, 47 of which being unsolved, glycomics profiling was performed of total plasma glycoproteins. Combination with whole-exome sequencing in 31 cases revealed a known genetic defect in 15 individuals. To identify additional genetic factors, hierarchical clustering of the plasma glycomics data was done, which indicated a subgroup of four patients that shared a unique glycomics signature of hybrid type N-glycans. In two siblings, compound heterozygous mutations were found in SLC10A7, a gene of unknown function in human. These included a missense mutation that disrupted transmembrane domain 4 and a mutation in a splice acceptor site resulting in skipping of exon 9. The two other individuals showed a complete loss of SLC10A7 mRNA. The patients' phenotype consisted of amelogenesis imperfecta, skeletal dysplasia, and decreased bone mineral density compatible with osteoporosis. The patients' phenotype was mirrored in SLC10A7 deficient zebrafish. Furthermore, alizarin red staining of calcium deposits in zebrafish morphants showed a strong reduction in bone mineralization. Cell biology studies in fibroblasts of affected individuals showed intracellular mislocalization of glycoproteins and a defect in post-Golgi transport of glycoproteins to the cell membrane. In contrast to yeast, human SLC10A7 localized to the Golgi. Our combined data indicate an important role for SLC10A7 in bone mineralization and transport of glycoproteins to the extracellular matrix.

• MeSH
• dánio pruhované genetika   růst a vývoj   metabolismus   MeSH
• dospělí MeSH
• exom MeSH
• fenotyp MeSH
• fibroblasty metabolismus   patologie   MeSH
• fyziologická kalcifikace * MeSH
• genomika * MeSH
• glykomika * MeSH
• glykopeptidasa nedostatek   MeSH
• glykosylace MeSH
• Golgiho aparát metabolismus   patologie   MeSH
• kohortové studie MeSH
• kojenec MeSH
• kultivované buňky MeSH
• lidé MeSH
• mladý dospělý MeSH
• mutace * MeSH
• přenašeče organických aniontů závislé na sodíku genetika   metabolismus   MeSH
• rodokmen MeSH
• symportéry genetika   metabolismus   MeSH
• transport proteinů MeSH
• vrozené poruchy glykosylace komplikace   MeSH
• vývojové onemocnění kostí etiologie   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH