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Background: Neonatal diabetes with congenital hypothyroidism (NDH) syndrome is a rare condition caused by homozygous or compound heterozygous mutations in the GLI-similar 3 coding gene GLIS3. Almost 20 patients have been reported to date, with significant phenotypic variability. Case presentation: We describe a boy with a homozygous deletion (exons 5-9) in the GLIS3 gene, who presents novel clinical aspects not reported previously. In addition to neonatal diabetes, congenital hypothyroidism and other known multi-organ manifestations such as cholestasis and renal cysts, he suffered from hyporegenerative anemia during the first four months of life and presents megalocornea in the absence of elevated intraocular pressure. Compensation of partial exocrine pancreatic insufficiency and deficiencies in antioxidative vitamins seemed to have exerted marked beneficial impact on several disease symptoms including cholestasis and TSH resistance, although a causal relation is difficult to prove. Considering reports on persistent fetal hemoglobin detected in a few children with GLIS3 mutations, the transient anemia seen in our patient may represent a further symptom associated with either the GLIS3 defect itself or, secondarily, micronutrient deficiency related to exocrine pancreatic deficiency or cholestasis. Conclusions: Our report expands the phenotypic spectrum of patients with GLIS3 mutations and adds important information on the clinical course, highlighting the possible beneficial effects of pancreatic enzyme and antioxidative vitamin substitutions on characteristic NDH syndrome manifestations such as TSH resistance and cholestasis. We recommend to carefully screen infants with GLIS3 mutations for subtle biochemical signs of partial exocrine pancreatic deficiency or to discuss exploratory administration of pancreatic enzymes and antioxidative vitamins, even in case of good weight gain and fecal elastase concentrations in the low-to-normal range. [ABSTRACT FROM AUTHOR]

Background: To investigate changes in diabetes treatment over the last two decades in three age-groups of children and adolescents with type 1 diabetes (T1D) from Germany and Austria. Methods: 63,967 subjects (<18yr) with T1D documented between 1995 and 2014 from the DPV-database were included and stratified according to age (0.5-<6, 6-<12, 12-<18yr). Regression models were applied for insulin regimens (<3 and ≥4 injection time points/day, or continuous subcutaneous insulin infusion (CSII)), use of rapid- and long acting insulin analogues, NPH insulin, and frequency of self-monitoring of blood glucose (SMBG)/day. Models were adjusted for sex, diabetes duration, and migration background. P-value for trend was given. Findings: The number of subjects with <3 injection time points/day decreased from 1995 to 2014 to <5% in all age-groups (p<0.0001). Proportion of patients with ≥4 injections/day increased until the early 2000s, and then declined until 2014. This trend was not found in 6-<12yr olds (p = 0.3403). CSII increased in all age-groups (p<0.0001) with the highest increase in children <6 years (from 0.4% to 79.2%), and the lowest increase in 12-<18 year olds (from 1.0% to 38.9%). NPH insulin decreased in all age-groups (p<0.0001). Insulin analogues, especially rapid-acting, became more frequent in all age-groups (p<0.0001), accounting for 78.4% in 2014 for all subjects. The highest use was found in the youngest children (in 2014: 85.6%), the lowest use in 6-<12 year olds (in 2014: 72.9%). The number of SMBG/day increased from 2.2 to 6.4 with a similar rise in all age-groups (p<0.0001). Frequency was highest in subjects <6yr. Conclusions: In all age-groups, T1D treatment was intensified over the last 20 years. Age-specific differences in trends were particularly observed in the number of patients on CSII, in the number of patients with 4 or more injections/day, and in the frequency of SMBG/day. [ABSTRACT FROM AUTHOR]