Novel and recurrent COMP gene variants in five Japanese patients with pseudoachondroplasia: skeletal changes from the neonatal to infantile periods

Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia caused by pathogenic variants of cartilage oligomeric matrix protein (COMP). Clinical symptoms of PSACH are characterized by growth disturbances after the first year of life. These disturbances lead to severe short stature with short limbs, brachydactyly, scoliosis, joint laxity, joint pain since childhood, and a normal face. Epimetaphyseal dysplasia, shortened long bones, and short metacarpals and phalanges are common findings on radiological examination. Additionally, anterior tonguing of the vertebral bodies in the lateral view is an important finding in childhood because it is specific to PSACH and normalizes with age. Here, we report five Japanese patients with PSACH, with one recurrent (p.Cys351Tyr) and four novel heterozygous pathogenic COMP variants (p.Asp437Tyr, p.Asp446Gly, p.Asp507Tyr, and p.Asp518Val). These five pathogenic variants were located in the calcium-binding type 3 (T3) repeats. In four of the novel variants, the affected amino acid was aspartic acid, which is abundant in each of the eight T3 repeats. We describe the radiological findings of these five patients. We also retrospectively analyzed the sequential changes in the vertebral body and epimetaphysis of the long bones from the neonatal to infantile periods in a patient with PSACH and congenital heart disease

1,25-Dihydroxyvitamin D(3) stimulates the secretion of insulin-like growth factor binding protein 3 (IGFBF-3) by cultured human osteosarcoma cells

Several types specific insulin-like growth factor binding proteins (IGFBPs) are produced by peripheral tissue-derived cells and they modulate the functions of insulin-like growth factors. In this study, both the secretion of IGFBP-3 from a human osteosarcoma cell line MG63 and effects of 1, 25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) on the production of IGFBP-3 were investigated. The β subunit of IGFBP-3 was detected immunocytochemically in the perinuclear cytoplasm of MG63 cells. Immunoblotting and SDS-PAGE analysis revealed that both 140-150KD MW entire molecules and 40-60KD MW β subinit molecules of IGFBP-3 were present in cell-conditionel media. 1,25-(OH)(2)D(3) stimulated the production of the IGFBP-3 molecule by MG63 cells. The concentration of IGFBP-3 conditioned media began to rise at 24 hours after the addtiton of 10(-9)M of 1,25-(OH)(2)D(3) and reached the peak level at 48 hours. Dose-dependent effects of 1,25-(OH)(2)D(3) were demonstrated. These findings show that MG63 produces IGFBP-3 and that 1,25-(OH)(2)D(3) stimulates the production of this protein. These findings suggest that the synergistic effects of 1,25-(OH)(2)D(3) on the action of IGF-I on osteoblastic cells may be modulated by locally produced IGFBP-3

A pediatric case of ureterolithiasis due to cystinuria accompanied by acute appendicitis; a case report

Introduction: Acute abdominal pain, a chief complaint frequently seen in the emergency department, can be triggered by a vast range of conditions. Although ureterolithiasis is a less common cause in children, renal colic can be caused by calculi due to hereditary metabolic diseases among patients in those age groups. Presentation of case: We report a 12-year-old girl with abdominal pain who was diagnosed with concurrent acute appendicitis and ureterolithiasis due to cystinuria. Acute appendicitis was successfully treated with cefmetazole, and the calculus was eliminated after adequate fluid loading. Discussion: Synchronous acute appendicitis and ureterolithiasis is reported to be rare. Cystinuria is a hereditary metabolic stone-forming disease, and the first calculi can be detected in childhood. Increasing the solubility of cystine in the urine is required to prevent recurrent stone formation and accompanying complications. Urinalysis, ultrasound, and computed tomography coincidentally demonstrated two different acute pathological processes of ureterolithiasis and appendicitis. Conclusion: Careful physical and laboratory examination can help clinicians find coexisting etiologies of acute abdominal pain. Ureterolithiasis can be seen in children with hereditary disorders such as cystinuria. Early diagnosis of cystinuria and close monitoring may lead to a better long-term outcome

Chylothorax in a 3-month-old boy with respiratory syncytial virus infection

　Chylothorax is a condition in which chyle leaks into the thoracic cavity. The causes of chylothorax can be nontraumatic, traumatic or idiopathic. The most common cause of nontraumatic chylothorax is obstruction of the thoracic duct by tumor. Traumatic chylothorax is caused by disruption of the thoracic duct, most often due to cardiac surgery or a thoracic surgical procedure, although in rare cases by cough or vomiting. We report the case of a 3-month-old boy with respiratory syncytial (RS) virus infection who presented with right chylothorax. No obstructive tumor mass was identified in the thoracic duct. Clinical symptoms of Noonan syndrome and Down syndrome, which often accompany lymphatic anomaly, were not found. Therefore, we speculate that his severe cough caused a high thoracic pressure and a disruption of the thoracic duct. He was treated by thoracocentesis and MCT milk. One month later, pleural effusion disappeared and did not recur. RS virus infection might be a rare cause of chylothorax in infants

Novel and recurrent COMP gene variants in five Japanese patients with pseudoachondroplasia: skeletal changes from the neonatal to infantile periods

Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia caused by pathogenic variants of cartilage oligomeric matrix protein (COMP). Clinical symptoms of PSACH are characterized by growth disturbances after the first year of life. These disturbances lead to severe short stature with short limbs, brachydactyly, scoliosis, joint laxity, joint pain since childhood, and a normal face. Epimetaphyseal dysplasia, shortened long bones, and short metacarpals and phalanges are common findings on radiological examination. Additionally, anterior tonguing of the vertebral bodies in the lateral view is an important finding in childhood because it is specific to PSACH and normalizes with age. Here, we report five Japanese patients with PSACH, with one recurrent (p.Cys351Tyr) and four novel heterozygous pathogenic COMP variants (p.Asp437Tyr, p.Asp446Gly, p.Asp507Tyr, and p.Asp518Val). These five pathogenic variants were located in the calcium-binding type 3 (T3) repeats. In four of the novel variants, the affected amino acid was aspartic acid, which is abundant in each of the eight T3 repeats. We describe the radiological findings of these five patients. We also retrospectively analyzed the sequential changes in the vertebral body and epimetaphysis of the long bones from the neonatal to infantile periods in a patient with PSACH and congenital heart disease