Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare, autosomal recessive inherited disease caused by the mutation of the FBP1 gene, the incidence is estimated to be between 1/350,000 and 1/900,000. The symptoms of affected individuals are non-specific and are easily confused with other metabolic disorders. The present study describes the clinical features of four Chinese pediatric patients who presented with hypoglycemia, hyperlactacidemia, metabolic acidosis, and hyperuricemia. Targeted-next generation sequencing using the Agilent SureSelect XT Inherited Disease Panel was used to screen for causal variants in the genome, and the clinically-relevant variants were subsequently verified using Sanger sequencing. Here, DNA sequencing identified six variations of the FBP1 gene (NM_000507.3) in the four patients. In Case 1, we found a compound heterozygous mutations of c.704delC (p.Pro235GlnfsX42) (novel) and c.960_961insG (p.Ser321Valfs) (known pathogenic). In Case 2, we found a compound heterozygous mutations of c.825 + 1G>A and c.960_961insG (both were known pathogenically). In Case 3, a homozygous missense mutation of c.355G>A (p.Asp119Asn) (reported in ClinVar database without functional study) was found. Case 4 had a compound heterozygous mutations c.720_729del (p.Tyr241GlyfsX33) (novel) and c.490G>A (p.Gly164Ser) (known pathogenically). Further in vitro studies in the COS-7cell line demonstrated that the mutation of ASP119ASN had no impact on protein expression, but decreased the enzyme activity, and with which the clinical significance of Asp119Asn can be determined to be likely pathogenic. This report not only expands upon the known spectrum of variation of the FBP1 gene, but also deepens our understanding of the clinical features of FBPase deficiency.

This study is aimed at examining the impact of ChatGPT on pediatric endocrine and metabolic conditions, particularly in the areas of screening and diagnosis, in both Chinese and English modes. A 40-question questionnaire covering the four most common pediatric endocrine and metabolic conditions was posed to ChatGPT in both Chinese and English three times each. Six pediatric endocrinologists evaluated the responses. ChatGPT performed better when responding to questions in English, with an unreliable rate of 7.5% compared to 27.5% for Chinese questions, indicating a more consistent response pattern in English. Among the reliable questions, the answers were more comprehensive and satisfactory in the English mode. We also found disparities in ChatGPT’s performance when interacting with different target groups and diseases, with improved performance for questions posed by clinicians in English and better performance for questions related to diabetes and overweight/obesity in Chinese for both clinicians and patients. Language comprehension, providing incomprehensive answers, and errors in key data were the main contributors to the low scores, according to reviewer feedback.Conclusion: Despite these limitations, as ChatGPT continues to evolve and expand its network, it has significant potential as a practical and effective tool for clinical diagnosis and treatment. What is Known:• The deep learning-based large-language model ChatGPT holds great promise for improving clinical practice for both physicians and patients and has the potential to increase the speed and accuracy of disease screening and diagnosis, as well as enhance the overall efficiency of the medical process. However, the reliability and appropriateness of AI model responses in specific field remains unclear.• This study focused on the reliability and appropriateness of AI model responses to straightforward and fundamental questions related to the four most prevalent pediatric endocrine and metabolic disorders, for both healthcare providers and patients, in different language scenarios. What is New:• The AI model performed better when responding to questions in English, with more consistent, as well as more comprehensive and satisfactory responses. In addition, we also found disparities in ChatGPT’s performance when interacting with different target groups and different diseases.• Despite these limitations, as ChatGPT continues to evolve and expand its network, it has significant potential as a practical and effective tool for clinical diagnosis and treatment.

Background: Bardet-Biedl syndrome (BBS) is a type of non-motile ciliopathy. To date, 26 genes have been reported to be associated with BBS. However, BBS is genetically heterogeneous, with significant clinical overlap with other ciliopathies, which complicates diagnosis. Disability and mortality rates are high in BBS patients; therefore, it is urgent to improve our understanding of BBS. Thus, our study aimed to describe the genotypic and phenotypic spectra of BBS in China and to elucidate genotype–phenotype correlations. Methods: Twenty Chinese patients diagnosed with BBS were enrolled in this study. We compared the phenotypes of Chinese BBS patients in this study with those from other countries to analyze the phenotypic differences across patients worldwide. In addition, genotype–phenotype correlations were described for our cohort. We also summarized all previously reported cases of BBS in Chinese patients (71 patients) and identified common and specific genetic variants in the Chinese population. Results: Twenty-eight variants, of which 10 are novel, in 5 different BBS-associated genes were identified in 20 Chinese BBS patients. By comparing the phenotypes of BBSome-coding genes (BBS2,7,9) with those of chaperonin-coding genes (BBS10,12), we found that patients with mutations in BBS10 and 12 had an earlier age of onset (1.10 Vs. 2.20, p < 0.01) and diagnosis (4.64 Vs. 13.17, p < 0.01), whereas patients with mutations in BBS2, 7, and 9 had a higher body mass index (28.35 Vs. 24.21, p < 0.05) and more vision problems (p < 0.05). Furthermore, in 91 Chinese BBS patients, mutations were predominant in BBS2 (28.89%) and BBS7 (15.56%), and the most frequent variants were in BBS2: c.534 + 1G > T (10/182 alleles) and BBS7: c.1002delT (7/182 alleles), marking a difference from the genotypic spectra of BBS reported abroad. Conclusions: We recruited 20 Chinese patients with BBS for genetic and phenotypic analyses, and identified common clinical manifestations, pathogenic genes, and variants. We also described the phenotypic differences across patients worldwide and among different BBS-associated genes. This study involved the largest cohort of Chinese patients with BBS, and provides new insights into the distinctive clinical features of specific pathogenic variants.

Background: In this study, we analysed the clinical and genetic characteristics and follow‐up data of patients with maturity‐onset diabetes of the young (MODY). Methods: From January 2015 to December 2022, patients with persistent hyperglycaemia suspected of having monogenic diabetes or diabetes syndrome were recruited, and next‐generation sequencing (NGS) was performed at the Shanghai Children’s Medical Center. Patients’ clinical and laboratory findings were recorded preceding follow‐ups. Candidate variants were verified using Sanger sequencing. Variant pathogenicity was evaluated according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Genetic testing was performed in 175 children. MODY‐related pathogenic or likely pathogenic gene variants were identified in 30 patients from different families. Of these, 11 were diagnosed with GCK ‐MODY (36.7%), six with INS ‐MODY (20%), five with HNF1A ‐MODY (16.7%), five with ABCC8 ‐MODY (16.7%), two with HNF1B ‐MODY (6.7%) and one with HNF4A ‐MODY (3.3%). There was one shift variant and seven splice‐site variants, and the rest were missense variants. We discovered six novel variants. Of the 30 patients, 63.3% had a family history of diabetes, 13.3% had diabetic ketoacidosis (DKA), and 16.7% had positive diabetes‐associated autoantibodies. The diabetes phenotype of patients with the INS variant was similar to that of patients with type 1 diabetes. All patients, including those having positive autoantibodies, required long‐term insulin therapy during follow‐ups. Four patients with the ABCC8 variant were unable to switch to oral sulfonylurea therapy and continued insulin therapy. Conclusion: Genetic testing is helpful for the precise diagnosis and treatment of patients with MODY, including those with DKA history and positive diabetes autoantibody. GCK ‐MODY is the most common type of MODY, and patients with INS variant account for a relatively large proportion of MODY cases in our cohort.

Background Bardet-Biedl syndrome (BBS) is a type of non-motile ciliopathy. To date, 26 genes have been reported to be associated with BBS. However, BBS is genetically heterogeneous, with significant clinical overlap with other ciliopathies, which complicates diagnosis. Disability and mortality rates are high in BBS patients; therefore, it is urgent to improve our understanding of BBS. Thus, our study aimed to describe the genotypic and phenotypic spectra of BBS in China and to elucidate genotype-phenotype correlations. Methods Twenty Chinese patients diagnosed with BBS were enrolled in this study. We compared the phenotypes of Chinese BBS patients in this study with those from other countries to analyze the phenotypic differences across patients worldwide. In addition, genotype-phenotype correlations were described for our cohort. We also summarized all previously reported cases of BBS in Chinese patients (71 patients) and identified common and specific genetic variants in the Chinese population. Results Twenty-eight variants, of which 10 are novel, in 5 different BBS-associated genes were identified in 20 Chinese BBS patients.. By comparing the phenotypes of BBSome-coding genes (BBS2,7,9) with those of chaperonin-coding genes (BBS10,12), we found that patients with mutations in BBS10 and 12 had an earlier age of onset (1.10 Vs. 2.20, p < 0.01) and diagnosis (4.64 Vs. 13.17, p < 0.01), whereas patients with mutations in BBS2, 7, and 9 had a higher body mass index (28.35 Vs. 24.21, p < 0.05) and more vision problems (p < 0.05). Furthermore, in 91 Chinese BBS patients, mutations were predominant in BBS2 (28.89%) and BBS7 (15.56%), and the most frequent variants were in BBS2: c.534 + 1G > T (10/182 alleles) and BBS7: c.1002delT (7/182 alleles), marking a difference from the genotypic spectra of BBS reported abroad. Conclusions We recruited 20 Chinese patients with BBS for genetic and phenotypic analyses, and identified common clinical manifestations, pathogenic genes, and variants. We also described the phenotypic differences across patients worldwide and among different BBS-associated genes. This study involved the largest cohort of Chinese patients with BBS, and provides new insights into the distinctive clinical features of specific pathogenic variants.