Bardet-Biedl syndrome (BBS) is a rare autosomal recessively inherited disease with major clinical symptoms such as: obesity, retinal degeneration, polydactyly and renal abnormalities. The aim of the study was to assess the spectrum of gene variants among patients with BBS, identified on the basis of nationwide genetic studies of monogenic diabetes in Polish population. Out of 575 patients enrolled for genetic testing from February 2017 to July 2019, 25 patients with a clinical suspicion of BBS were selected. The identification of pathogenic variants was performed by using targeted next-generation sequencing (NGS) on Illumina NextSeq 550 platform involving the SureSelect assay (Agilent, Santa Clara, CA, USA). BBS was genetically confirmed in 10 of 25 suspected patients. In patients, 14 different variants were found in six genes, mainly in BBS9 and BBS10 gene, including two novel variants. A strong association between hyperglycemia and insulin resistance in patients and the presence of variants in BBS9 gene was observed. Identification of 14 variants, including two new mutations using the NGS method, is the first molecular characteristic of Polish patients with Bardet–Biedl syndrome. It gives hope for earlier proper diagnosis of BBS in future patients selected from children with early childhood obesity and their medical multidisciplinary care.

Background: Recognizing insulin resistance (IR) in children remains challenging due to uncertain IRI-HOMA cut-offs and unclear recommendations for evaluating IR based on OGTT. In our study, we compare the effectiveness of IRI-HOMA and IRI-Belfiore (OGTT-based) in detecting IR and its metabolic complications in children. Methods: The analysis included 553 children who were hospitalized at the Department of Endocrinology and Metabolic Diseases of the Polish Mother’s Memorial Hospital Research Institute (PMMH-RI) in Lodz, Poland, between 2002 and 2018 due to various reasons—of these, 67.5% were girls. All underwent OGTT for glucose and insulin assessment. IR diagnosis relied on IRI-HOMA and IRI-Belfiore. IR based on IRI-HOMA was evaluated using three criteria: (A) >2.5; (B) >2.67 in boys and >2.22 in girls before puberty and >5.22 and >3.82 during puberty, respectively; (C) >95th percentile according to charts for IRI-HOMA in children. Results: Prepubertal children exhibited significantly lower IRI-HOMA and IRI-Belfiore than their pubertal counterparts (p < 0.00005). IRI-HOMA and IRI-Belfiore values positively correlated with age and BMI SDS value (p < 0.000001 for all calculations). As many as 26% to 46.9% of children with normal IRI-HOMA showed elevated IRI-Belfiore, with notably higher levels of triglycerides, a lower HDL cholesterol fraction, and a lower HDL/total cholesterol ratio in this subgroup. Conclusions: A notable proportion of children exhibited elevated IRI-Belfiore levels despite having normal IRI-HOMA values. This suggests the possibility of peripheral IR preceding hepatic IR in children—omitting an OGTT may therefore lead to overlooking cases of IR. Children diagnosed with IR via OGTT displayed significantly poorer lipid profiles compared to those without IR (characterized by normal values in both IRI-HOMA and IRI-Belfiore). This underscores the ability of OGTT-derived IR indices to identify individuals at risk of developing complications associated with obesity and IR before the onset of metabolic syndrome (MS) symptoms. If IR is already detected in children based on fasting glucose and insulin levels (IRI-HOMA), further evaluation may not be warranted, as OGTT results often simply confirm the diagnosis.

Bardet–Biedl syndrome (BBS) and Alström syndrome (ALMS) are rare multisystem diseases with an autosomal recessive mode of inheritance and genetic heterogeneity, characterized by visual impairment, hearing impairment, cardiomyopathy, childhood obesity, and insulin resistance. The purpose of our study was to evaluate the indicators of nervous system changes occurring in patients with ALMS and BBS using optical coherence tomography (OCT) and magnetic resonance spectroscopy (MRS) methods compared to a group of healthy subjects. The OCT results showed significantly lower macular thickness in the patient group compared to the control group (p = 0.002). The MRS study observed differences in metabolite levels between the study and control groups in brain areas such as the cerebellum, thalamus, and white matter. After summing the concentrations from all areas, statistically significant results were obtained for N-acetylaspartate, total N-acetylaspartate, and total creatine. Concentrations of these metabolites were reduced in ALMS/BBS patients by 38% (p = 0.0004), 35% (p = 0.0008), and 28% (p = 0.0005), respectively. Our results may help to understand the pathophysiology of these rare diseases and identify strategies for new therapies.