OBJECTIVE: To explore the clinical features and genetic etiology in a child with Hereditary hemorrhagic telangiectasia (HHT) complicated by growth hormone deficiency. METHODS: A child presented at Yantai Yuhuangding Hospital in October 2014 for "short stature for over 4 years" was selected as the study subject. Peripheral venous blood samples were collected from the child and his parents for genomic DNA extraction and whole-exome sequencing (WES). The pathogenicity of the candidate variants was assessed by following the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2025-003). RESULTS: The patient, a 4-year-and-2-month-old male, presented with short stature and recurrent epistaxis since early childhood. Initial diagnosis of GHD was made via growth hormone stimulation testing. During follow-up, telangiectatic macules and polycythemia gradually appeared. WES revealed that he has harbored a heterozygous c.1807G>A (p.Gly603Arg) variant of the ENG gene, which was absent in both parents and classified as likely pathogenic based on ACMG guidelines. Sanger sequencing confirmed the candidate variant to be de novo. CONCLUSION Patients with HHT combined with GHD may exhibit clinical features such as short stature, telangiectasia, and arteriovenous malformations. The heterozygous c.1807G>A (p.Gly603Arg) variant of the ENG gene probably underlay the pathogenesis of the disease in the proband. Above finding has expanded the mutational spectrum of the ENG gene.
Humans ; Telangiectasia, Hereditary Hemorrhagic/complications* ; Male ; Child, Preschool ; Phenotype ; Endoglin/genetics* ; Mutation ; Human Growth Hormone/deficiency* ; Exome Sequencing

OBJECTIVE: To analyze the clinical and genetic characteristics of a Chinese pedigree affected with congenital Isolated growth hormone deficiency (IGHD). METHODS: A pedigree presenting with Pituitary stalk interruption syndrome (PSIS) (including the proband, his two younger sisters and both parents) who had visited the Capital Institute of Pediatrics Affiliated to Capital Medical University in September 2020 was selected as the study subject. Clinical data were collected. Peripheral blood samples were collected from the proband and his family members. Following the extraction of genomic DNA, whole-exome sequencing (WES) was carried out, and candidate variants were validated by Sanger sequencing. The pathogenicity of the candidate variants was classified based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the Institute Pediatrics of Capital Medical University (Ethics No.: SHERLL2025033). RESULTS: The proband and one younger sister (Ⅱ3) presented with growth retardation, short stature, and a doll-like facies. Another younger sister (Ⅱ2) and both parents had normal heights and appearance. Sanger sequencing confirmed that the proband and his younger sister (Ⅱ3) both harbored compound heterozygous variants of the GHRHR gene, namely c.776C>A (p.T259K) and c.1166G>A (p.R389Q). The other younger sister (Ⅱ2) and the parents were heterozygous carriers. The c.1166G>A (p.R389Q) variant was unreported previously. Based on the guidelines from the ACMG, it was classified as variant of uncertain significance (PM2_Supporting+BP4). Bioinformatics analysis indicated a deleterious effect on the protein function. CONCLUSION Variants of the GHRHR gene probably underlay the pathogenesis of IGHD in this pedigree. Above finding has provided a basis for the clinical diagnosis and genetic counseling for this family.
Child ; Female ; Humans ; Male ; China ; Dwarfism, Pituitary/genetics* ; Exome Sequencing ; Human Growth Hormone/deficiency* ; Mutation ; Pedigree ; Receptors, Neuropeptide/genetics* ; Receptors, Pituitary Hormone-Regulating Hormone/genetics* ; East Asian People/genetics*

Consensus ; Growth Disorders ; diagnosis ; drug therapy ; Hormone Replacement Therapy ; Human Growth Hormone ; administration & dosage ; deficiency ; therapeutic use ; Humans ; Practice Guidelines as Topic

Neurofibromatosis Type 1 (NF1) is an autosomal dominant genetic disorder caused by NF1 gene mutations. Café au lait spots, neurofibromatosis, Lisch nodules, axillary freckling, dermal neurofibromas and skeletal dysplasia are the most common manifestations for this disease. A 11-year-old boy visited Third Xiangya Hospital, Central South University due to growth-retardation. He was eventually diagnosed as NF1 with growth hormone deficiency. A novel heterozygous splicing mutation c.6579+2 T>C (IVS 34+2 T>C) of NF1 gene was identified in the patient and his mother. Considering NF1 may present with short stature due to growth hormone deficiency, all children with short stature combined with café au lait spots should be screened for NF1, which may assist the clinical diagnosis and the genetic counseling.
Cafe-au-Lait Spots ; diagnosis ; genetics ; Child ; Genes, Neurofibromatosis 1 ; Growth Hormone ; deficiency ; Humans ; Male ; Mutation ; Neurofibromatosis 1 ; blood ; diagnosis

This study examined the characteristics of biochemical parameters, bone diseases, and vascular calcification in Korean patients with chronic kidney disease (CKD) not yet on dialysis. Serum levels of fibroblast growth factor 23 (FGF23), intact parathyroid hormone (iPTH), 25-hydroxyvitamin D3 (25D), and 1,25-dihydroxyvitamin D3 (1,25D); lumbar spine, total hip, and femur neck bone mineral densities; and brachial-to-ankle pulse wave velocity (baPWV) representing vascular calcification were measured at baseline for 2,238 CKD patients in the KoreaN Cohort Study for Outcomes in Patients With CKD (KNOW-CKD). Increases in serum FGF23 and iPTH preceded changes in serum calcium and phosphate, similar to Western populations. However, the 25D and 1,25D levels decreased earlier than serum FGF23 or iPTH increased, with a decreased estimated glomerular filtration rate (eGFR) in Korean CKD patients. Vitamin D deficiency occurred in 76.7% of patients with CKD stage 1. Bone mineral densities were lowest in CKD stage 5 (lumbar spine, −0.64 ± 1.67; total hip, −0.49 ± 1.21; femur neck, −1.02 ± 1.25). Osteoporosis was more prevalent in patients with higher CKD stages. The mean baPWV, abdominal aortic calcification (AAC), and coronary calcium score also increased, with declined eGFR. In conclusion, a decline in serum vitamin D levels was observed in early CKD stages before significant increases of FGF23 and iPTH in the Korean CKD population compared with that in Western populations. Increased bone disease and vascular calcification occurred in early-stage CKD.
Bone Density ; Bone Diseases ; Calcifediol ; Calcitriol ; Calcium ; Cohort Studies* ; Dialysis ; Femur Neck ; Fibroblast Growth Factors ; Glomerular Filtration Rate ; Hip ; Humans ; Kidney* ; Osteoporosis ; Parathyroid Hormone ; Pulse Wave Analysis ; Renal Insufficiency, Chronic* ; Spine ; Vascular Calcification ; Vitamin D ; Vitamin D Deficiency

BACKGROUND: Vitamin D deficiency remains common in all age groups and affects skeletal and non-skeletal health. Fibroblast growth factor 23 is a bone-derived hormone that regulates phosphate and 1,25-dihydroxyvitamin D homeostasis as a counter regulatory factor. 1,25-Dihydroxyvitamin D stimulates fibroblast growth factor 23 synthesis in bone, while fibroblast growth factor 23 suppresses 1,25-dihydroxyvitamin D production in the kidney. The aim of this study was to evaluate the effects of vitamin D₃ intramuscular injection therapy on serum fibroblast growth factor 23 concentrations, and several other parameters associated with bone metabolism such as sclerostin, dickkopf-1, and parathyroid hormone. METHODS: A total of 34 subjects with vitamin D deficiency (defined by serum 25-hydroxyvitamin D levels below 20 ng/mL) were randomly assigned to either the vitamin D injection group (200,000 units) or placebo treatment group. Serum calcium, phosphate, urine calcium/creatinine, serum 25-hydroxyvitamin D, fibroblast growth factor 23, sclerostin, parathyroid hormone, and dickkopf-1 levels were serially measured after treatment. RESULTS: Comparing the vitamin D injection group with the placebo group, no significant changes were observed in serum fibroblast growth factor 23, parathyroid hormone, or dickkopf-1 levels. Serum sclerostin concentrations transiently increased at week 4 in the vitamin D group. However, these elevated levels declined later and there were no statistically significant differences as compared with baseline levels. CONCLUSION: Serum fibroblast factor 23, sclerostin, parathyroid hormone, and dickkopf-1 levels were not affected significantly by single intramuscular injection of vitamin D₃.
Calcium ; Cholecalciferol ; Fibroblast Growth Factors* ; Fibroblasts* ; Homeostasis ; Humans ; Injections, Intramuscular ; Kidney ; Metabolism ; Parathyroid Hormone ; Vitamin D Deficiency* ; Vitamin D* ; Vitamins*

Objective To evaluate physicians' attitude and knowledge about the management of adult growth hormone deficiency (AGHD) at Peking Union Medical College Hospital and impact factors associated with better decision-making.Methods A 21-question anonymous survey was distributed and collected at Peking Union Medical College Hospital, a major teaching hospital in Chinese Academy of Medical Sciences. Data of physicians' educational background, clinical training, patient workload per year and continuing medical education in AGHD were collected. Factors associated with appropriate answers were further analyzed by multivariate regression models.Results One hundred and eighteen internal medicine residents, endocrine fellows, attending physicians and visiting physicians responded to the survey. Among them, 44.9% thought that AGHD patients should accept recombinant human growth hormone replacement therapy. Moreover, 56.8% selected insulin tolerance test and growth hormone-releasing hormone-arginine test for the diagnosis of AGHD. Logistic regression analysis of physician demographic data, educational background, and work experience found no consistent independent factors associated with better decision-making, other than continued medical education, that were associated with treatment choice.Conclusions The physicians' reported management of AGHD in this major academic healthcare center in Beijing was inconsistent with current evidence. High quality continued medical education is required to improve Chinese physician management of AGHD.
Adult ; Aged ; Education, Medical, Continuing ; Female ; Health Knowledge, Attitudes, Practice ; Hormone Replacement Therapy ; Human Growth Hormone ; deficiency ; Humans ; Logistic Models ; Male ; Middle Aged

OBJECTIVETo assess the diagnostic value of the propranolol-exercise provocative test for growth hormone deficiency (GHD) in children.

METHODSThis study included 120 children who received both the insulin provocative test and the propranolol-exercise provocative test due to short stature between January 2009 and March 2013. Growth hormone (GH) levels in venous blood were measured before and after the provocative test. Peak GH <10 ng/mL was defined as negative stimulation, while peak GH ≥10 ng/mL was defined as positive stimulation. The children whose peak GH levels were <10 ng/ mL after both tests were diagnosed with GHD.

RESULTSTwenty-nine (24.2%) of the 120 children with short stature were diagnosed with GHD. The positive rate in the insulin provocative test was 48.3%, versus 65.8% in the propranolol-exercise provocative test. The overall coincidence rate and positive coincidence rate of the two tests were 62.5% and 79.3%, respectively. The peak GH after the propranolol-exercise provocative test was significantly higher than that after the insulin provocative test (P<0.01). Peak GH occurred mostly at 30-60 minutes after the insulin provocative test, while that occurred mostly at 120 minutes after the propranolol-exercise provocative test. No adverse effects were observed in the propranolol-exercise provocative test.

CONCLUSIONSCoincidence rates in stimulating the secretion of GH are high between the propranolol-exercise provocative test and the insulin provocative test. Compared with the insulin provocative test, the propranolol-exercise provocative test is more likely to stimulate the secretion of GH. GHD can be clinically diagnosed by the insulin provocative test combined with the propranolol-exercise provocative test.

Adolescent ; Child ; Child, Preschool ; Exercise ; Female ; Human Growth Hormone ; blood ; deficiency ; Humans ; Insulin ; Male ; Propranolol

Abdomen ; Child, Preschool ; Female ; Human Growth Hormone ; deficiency ; Humans ; Lipodystrophy ; etiology

Child, Preschool ; Chromosomes, Human, Pair 18 ; Female ; Human Growth Hormone ; deficiency ; Humans ; Ring Chromosomes