Wolfram Syndrome type 2 (WFS2) is considered a phenotypic and genotypic variant of WFS, whose minimal criteria for diagnosis are diabetes mellitus and optic atrophy. The disease gene for WFS2 is CISD2. The clinical phenotype of WFS2 differs from WFS1 for the absence of diabetes insipidus and psychiatric disorders, and for the presence of bleeding upper intestinal ulcers and defective platelet aggregation. After the first report of consanguineous Jordanian patients, no further cases of WFS2 have been reported worldwide. We describe the first Caucasian patient affected by WFS2. The proband was a 17 year-old girl. She presented diabetes mellitus, optic neuropathy, intestinal ulcers, sensorineural hearing loss, and defective platelet aggregation to ADP. Genetic testing showed a novel homozygous intragenic deletion of CISD2 in the proband. Her brother and parents carried the heterozygous mutation and were apparently healthy, although they showed subclinical defective platelet aggregation. Long runs of homozygosity analysis from SNP-array data did not show any degree of parental relationship, but the microsatellite analysis confirmed the hypothesis of a common ancestor. Our patient does not show optic atrophy, one of the main diagnostic criteria for WFS, but optic neuropathy. Since the “asymptomatic” optic atrophy described in Jordanian patients is not completely supported, we could suppose that the ocular pathology in Jordanian patients was probably optic neuropathy and not optic atrophy. Therefore, as optic atrophy is required as main diagnostic criteria of WFS, it might be that the so-called WFS2 could not be a subtype of WFS. In addition, we found an impaired aggregation to ADP and not to collagen as previously reported, thus it is possible that different experimental conditions or inter-patient variability can explain different results in platelet aggregation. Further clinical reports are necessary to better define the clinical spectrum of this syndrome and to re-evaluate its classification.

Aims The purpose of this work is to find the gut microbial fingerprinting of pediatric patients with type 1 diabetes. Methods The microbiome of 31 children with type 1 diabetes at onset and of 25 healthy children was determined using multiple polymorphic regions of the 16S ribosomal RNA. We performed machine-learning analyses and metagenome functional analysis to identify significant taxa and their metabolic pathways content. Results Compared with healthy controls, patients showed a significantly higher relative abundance of the following most important taxa: Bacteroides stercoris, Bacteroides fragilis, Bacteroides intestinalis, Bifidobacterium bifidum, Gammaproteobacteria and its descendants, Holdemania, and Synergistetes and its descendants. On the contrary, the relative abundance of Bacteroides vulgatus, Deltaproteobacteria and its descendants, Parasutterella and the Lactobacillus, Turicibacter genera were significantly lower in patients with respect to healthy controls. The predicted metabolic pathway more associated with type 1 diabetes patients concerns “carbon metabolism,” sugar and iron metabolisms in particular. Among the clinical variables considered, standardized body mass index, anti-insulin autoantibodies, glycemia, hemoglobin A_1c, Tanner stage, and age at onset emerged as most significant positively or negatively correlated with specific clusters of taxa. Conclusions The relative abundance and supervised analyses confirmed the importance of B stercoris in type 1 diabetes patients at onset and showed a relevant role of Synergistetes and its descendants in patients with respect to healthy controls. In general the robustness and coherence of the showed results underline the relevance of studying the microbioma using multiple polymorphic regions, different types of analysis, and different approaches within each analysis.

The fecal microbiome of 55 obese children and adolescents (BMI-SDS 3.2 ± 0.7) and of 25 normal-weight subjects, matched both for age and sex (BMI-SDS − 0.3 ± 1.1) was analysed. Streptococcus, Acidaminococcus, Sutterella, Prevotella, Sutterella wadsworthensis, Streptococcus thermophilus, and Prevotella copri positively correlated with obesity. The inferred pathways strongly associated with obesity concern the biosynthesis pathways of tyrosine, phenylalanine, tryptophan and methionine pathways. Furthermore, polyamine biosynthesis virulence factors and pro-inflammatory lipopolysaccharide biosynthesis pathway showed higher abundances in obese samples, while the butanediol biosynthesis showed low abundance in obese subjects. Different taxa strongly linked with obesity have been related to an increased risk of multiple diseases involving metabolic pathways related to inflammation (polyamine and lipopolysaccharide biosynthesis). Cholesterol, LDL, and CRP positively correlated with specific clusters of microbial in obese patients. The Firmicutes/Bacteroidetes-ratio was lower in obese samples than in controls and differently from the literature we state that this ratio could not be a biomarker for obesity.

Wolfram Syndrome (WS) is an autosomal recessive neurodegenerative disorder characterized by Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness identified by the acronym “DIDMOAD”. The WS gene, WFS1, encodes a transmembrane protein called Wolframin, which recent evidence suggests may serve as a novel endoplasmic reticulum calcium channel in pancreatic β-cells and neurons. WS is a rare disease, with an estimated prevalence of 1/550.000 children, with a carrier frequency of 1/354. The aim of our study was to determine the genotype of WS patients in order to establish a genotype/phenotype correlation. We clinically evaluated 9 young patients from 9 unrelated families (6 males, 3 females). Basic criteria for WS clinical diagnosis were coexistence of insulin-treated diabetes mellitus and optic atrophy occurring before 15 years of age. Genetic analysis for WFS1 was performed by direct sequencing. Molecular sequencing revealed 5 heterozygous compound and 3 homozygous mutations. All of them were located in exon 8, except one in exon 4. In one proband only an heterozygous mutation (A684V) was found. Two new variants c.2663 C>A and c.1381 A>C were detected. Our study increases the spectrum of WFS1 mutations with two novel variants. The male patient carrying the compound mutation [c.1060_1062delTTC]+[c.2663 C>A] showed the most severe phenotype: diabetes mellitus, optic atrophy (visual acuity 5/10), deafness with deep auditory bilaterally 8000 Hz, diabetes insipidus associated to reduced volume of posterior pituitary and pons. He died in bed at the age of 13 years. The other patient carrying the compound mutation [c.409_424dup16]+[c.1381 A>C] showed a less severe phenotype (DM, OA).