Lesch-Nyhan Syndrome in a Chinese Family with Mutation in the Hypoxanthine-Guanine Phosphoribosyltransferase Gene.

BACKGROUND: Lesch-Nyhan syndrome (LNS) is a congenital X-linked recessive neurogenetic disorder caused by mutations in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene. The main clinical manifestation includes hyperuricemia, juvenile-onset gouty arthritis, and neurological developmental disorders. Studies have reported more than 400 HPRT gene mutation sites, but the incidence of LNS in the Chinese population is extremely low. METHODS: Here we report a 16-year-old male patient who suffered neurological dysfunction at an early age and gouty arthritis in his youth. RESULTS: No activity of the HPRT enzyme was detected in the erythrocytes. Furthermore, we found a mutation on exon 3 of the HPRT gene in the patient and his mother (exon 3: c.143G>A), which resulted in arginine to histidine (p.R48H) substitution in the encoded protein. The same mutation was reported in several European families, but was found for the first time in a Chinese family. CONCLUSIONS: Clinicians in China have poor experience in diagnosing LNS cases due to the low incidence in China. Therefore, LNS screening for infants or adolescents with hyperuricemia, gouty arthritis, and neurological dysfunction should be performed.

Fahr's disease linked to a novel mutation in MYORG variants manifesting as paroxysmal limb stiffness and dysarthria: Case report and literature review.

BACKGROUND: Primary familial brain calcification (PFBC) is a rare hereditary neurodegenerative disorder associated with the MYORG gene; however, the clinical and radiological characteristics of MYORG-PFBC remain unclear. METHODS: We present relevant medical data obtained from a patient affected by PFBC with a novel MYORG variant and conducted a mutational analysis of MYORG in her family members. We reviewed all reported PFBC cases with biallelic MYORG mutations until April 1, 2023, and summarized the associated clinical and radiological features and mutation sites. RESULTS: The patient (22-year-old woman) exhibited paroxysmal limb stiffness and dysarthria for 3 years. Computed tomography revealed calcifications in the paraventricular white matter, basal ganglia, thalamus, and cerebellum. Whole-exome sequencing revealed a novel homozygous frameshift variant (c.743delG: p.G248Afs*32) in exon 2 of the MYORG gene (NM_020702.5). To date, 62 families and 64 mutation sites have been reported. Among the reported biallelic MYORG mutations, 57% were homozygous and 43% were compound heterozygous. Individuals with biallelic MYORG mutations experience more severe brain calcification with approximately 100% clinical penetrance. Ten single heterozygous mutation sites are associated with significant brain calcifications. CONCLUSION: All patients with primary brain calcification, particularly younger patients without a family history of the disease, should be screened for MYORG mutations.

Metformin Reduces Blood Glucose in Treatment-Naive Type 2 Diabetes by Altering the Gut Microbiome.

BACKGROUND: Our aim in this study was to better understand the causality of metformin and gut microbiome in the treatment of type 2 diabetes (T2D). METHODS: This study was conducted on individuals with newly diagnosed and treatment-naive T2D. We used 16S rRNA sequencing to assess the effect of metformin on composition and diversity of the gut microbiota. We also compared the differences in relative abundance of gut microbiome at the genus level in patients with treatment-naive T2D before and after 2 months of metformin treatment. Spearman's rank correlation coefficient analysis was used to identify genus abundance in relation to blood glucose and related factors. RESULTS: Metformin significantly reduced blood glucose and levels of the related factors in treatment-naive individuals with T2D after 2 months of treatment. The 16S rRNA sequencing showed that metformin treatment altered composition and diversity of gut microbiome. Megamonas and Klebsiella in the T2D groups were significantly higher compared with the control group. Metformin treatment caused a significant reduction in Megamonas and Klebsiella. Spearman's rank correlation coefficient analysis showed a significant positive correlation between Megamonas and blood glucose, glycated hemoglobin (A1C), serum fructosamine and alanine aminotranferase (ALT). Klebsiella showed a significant positive correlation between A1C and ALT. CONCLUSION: Metformin reduces blood glucose in T2D by interacting with different gut bacteria, possibly Megamonas and Klebsiella pneumoniae.