Congenital insensitivity to pain (CIP) comprises the rare heritable disorders without peripheral neuropathy that feature inability to feel pain. Fracturing and joint destruction are common complications, but lack detailed studies of mineral and skeletal homeostasis and bone histology. In 2013, discovery of a heterozygous gain-of-function mutation in SCN11A encoding voltage-gated sodium channel 1.9 (Nav1.9) established a distinctive CIP in three unrelated patients who suffered multiple painless fractures, self-inflicted mutilation, chronic diarrhea, and hyperhidrosis. Here, we studied a mother and two children with CIP by physical examination, biochemical testing, radiological imaging including DXA, iliac crest histology, and mutation analysis. She suffered fractures primarily of her lower extremities beginning at age two years, and had Charcot deformity of both ankles and joint hypermobility. Nerve conduction velocity and biopsy and electromyography were normal. Her children had recurrent major fractures beginning in early childhood, joint hypermobility, and chronic diarrhea. She had an excoriated external nare, and both children had hypertrophic scars from scratching. Skin collagen studies were normal. Radiographs revealed fractures and deformities. However, lumbar spine and total hip BMD Z-scores, biochemical parameters of mineral and skeletal homeostasis, and iliac crest histology of the mother (after in vivo tetracycline labeling) were normal. Genomic DNA from the children revealed a unique heterozygous missense mutation in exon 23 (c.3904C>T, p.Leu1302Phe) of SCN11A that is absent in SNP databases and alters an evolutionarily conserved amino acid. This autosomal dominant CIP reflects the second gain-of-function mutation of SCN11A. Perhaps joint hypermobility is an unreported feature. How mutation of Nav1.9 causes fracturing remains unexplained. Lack of injury awareness is typically offered as the reason, and was supported by our unremarkable biochemical, radiological, and histological findings indicating no skeletal pathobiology. However, low-trauma fracturing in these patients suggests an uncharacterized defect in bone quality.

Background Anti-seizure medication (ASM) treatment is one of the significant risk factors associated with abnormal vitamin D status in epilepsy patients. Multiple studies have shown that adult epilepsy patients can exhibit vitamin D deficiency. However, there are few reports investigating pediatric epilepsy patients. In this study, we aimed to identify risk factors related to hypovitaminosis D in pediatric epilepsy patients in Thailand. Methods A cross-sectional retrospective cohort study was conducted in 138 pediatric epilepsy patients who received anticonvulsants from April 2018 to January 2019. Demographic data, seizure types, puberty status, physical activity, duration, and types of anti-seizure medications were analyzed. Patients with abnormal liver function, abnormal renal function, and who received vitamin D supplements or ketogenic diet containing vitamin D were excluded. Levels of serum vitamin D (25(OH)D) were measured. Results All 138 subjects were enrolled, the age ranged from 1.04 – 19.96 years; (mean = 9.65 ± 5.09), the mean serum 25(OH) D level was 26.56 ± 9.67 ng/ml. The prevalence of vitamin D deficiency was 23.2% and insufficiency was 47.8% respectively. Two risk factors—puberty status (OR 5.43, 95% CI 1.879-15.67) and non-enzyme-inhibiting ASMs therapy (OR 3.58, 95% CI 1.117-11.46)—were significantly associated with hypovitaminosis D, as shown by multivariate analyses. Conclusions Our study reports the high prevalence of hypovitaminosis D in pediatric epilepsy patients in Thailand despite being located in the tropical zone. These findings can guide clinicians to measure vitamin D status in pediatric epilepsy patients particularly when they reach puberty and/or are using non-enzyme-inhibiting ASMs therapy. Early detection of vitamin D status and prompt vitamin D supplementation can prevent fractures and osteoporosis later in life. Trial registration TCTR20210215005 (http://www.clinicaltrials.in.th/).

To report case presenting with neonatal severe hyperparathyroidism Methods: A severe neonatal hyperparathyroidism was reviewed including demographic and clinical data.

Background: GnRH stimulation test is the gold standard for the diagnosis of central precocious puberty (CPP). However, it is invasive and costly. Previous studies showed that increased urinary gonadotropins (Gn) level in first morning voided (FMV) urine reflected the integration of elevated nocturnal Gn secretions. Therefore, it could be used to diagnose CPP. Nevertheless, its cutoff value for diagnosis of CPP is limited. Objective: To determine the association of Gn levels in FMV urine and serum during pubertal development and establish cutoff value of FMV urinary Gn as an alternative noninvasive method for diagnosis of CPP in girls. Methods: Sixty-one girls who had breast development before 8 years of age with sign of rapid pubertal progression (advanced bone age and/or increased height velocity) underwent subcutaneous GnRH agonist test. FMV urinary Gn were also collected on the same day. Both serum and urinary Gn levels were measured using electrochemiluminescence immunoassay (ECLIA) technique. The definite diagnosis of CPP is based on stimulated serum LH > 5 IU/L. FMV urinary Gn were compared between CPP and premature thelarche (PT) groups. The correlation between serum and urinary Gn were assessed and the cutoff value of urinary Gn to diagnose CPP was established. FMV urinary Gn of 480 Thai school girls (control) were also collected to determine the reference values according to their breast Tanner (BT) stages. Results: FMV ULH level in girls with CPP was significantly higher than that of PT (2.46 VS 0.8 IU/L; median, P <0.001). However, the level of ULH in PT group was not different from control group with BT1. FMV ULH and ULH: UFSH were well correlated with basal serum LH (r=0.63 and 0.73, respectively, Ps<0.001) and peak serum LH (r=0.44 and 0.54, respectively, Ps<0.001). Base on receiver operating characteristics analysis, basal serum LH was the best parameter to differentiate CPP from PT (area under the curve 0.797–0.926). ULH levels at ≥ 1.13 IU/L and ≥ 1.52 provide optimal sensitivity (72.3 and 68.1 %, respectively) and specificity (85.7 and 100 %, respectively). Combined ULH level ≥ 1.13 IU/L with ULH: UFSH ≥ 0.17 increased specificity from 85.7 to 92.9 % for predicting a positive GnRH agonist test. (peak LH ≥ 5 IU/L) Conclusions: First morning voided urinary Gn levels measurement is a highly potential method for the diagnosis of CPP in girls due to its good correlation with GnRH agonist test. Further study in a larger number of patients with close monitoring of clinical outcome is required before recommending as a standard investigation in CPP.