Cord Blood Stem Cell Transplantation ; Female ; Humans ; Infant ; Osteopetrosis ; therapy

Objective: To investigate the clinical presentation and genetic characteristics of malignant infantile osteopetrosis. Methods: This was a retrospective case study. Thirty-seven children with malignant infantile osteopetrosis admitted into Beijing Children's Hospital from January 2013 to September 2022 were enrolled in this study. According to the gene mutations, the patients were divided into the CLCN7 group and the TCIRG1 group. Clinical characteristics, laboratory tests, and prognosis were compared between two groups. Wilcoxon test or Fisher exact test were used in inter-group comparison. The survival rate was estimated with the Kaplan-Meier method and the Log-Rank test was used to compare the difference in survival between groups. Results: Among the 37 cases, there were 22 males and 15 females. The age of diagnosis was 0.5 (0.2, 1.0) year. There were 13 patients (35%) and 24 patients (65%) with mutations in CLCN7 and TCIRGI gene respectively. Patients in the CLCN7 group had an older age of diagnosis than those in the TCIRGI group (1.2 (0.4, 3.6) vs. 0.4 (0.2, 0.6) years, Z=-2.60, P=0.008). The levels of serum phosphorus (1.7 (1.3, 1.8) vs. 1.1 (0.8, 1.6) mmol/L, Z=-2.59, P=0.010), creatine kinase isoenzyme (CK-MB) (457 (143, 610) vs. 56 (37, 82) U/L, Z=-3.38, P=0.001) and the level of neutrophils (14.0 (9.9, 18.1) vs. 9.2 (6.7, 11.1) ×10⁹/L, Z=-2.07, P=0.039) at diagnosis were higher in the CLCN7 group than that in the TCIRG1 group. However, the level of D-dimer in the CLCN7 group was lower than that in the TCIRGI group (2.7 (1.0, 3.1) vs. 6.3 (2.5, 9.7) μg/L, Z=2.83, P=0.005). After hematopoietic stem cell transplantation, there was no significant difference in 5-year overall survival rate between the two groups (92.3%±7.4% vs. 83.3%±7.6%, χ²=0.56, P=0.456). Conclusions: TCIRGI gene mutations are more common in children with osteopetrosis. Children with TCIRGI gene mutations have younger age, lower levels of phosphorus, CK-MB, and neutrophils and higher level of D-dimer at the onset. After hematopoietic stem cell transplantation, patients with CLCN7 or TCIRGI gene mutations have similar prognosis.
Child ; Male ; Female ; Humans ; Osteopetrosis/therapy* ; Retrospective Studies ; Prognosis ; Genes, Recessive ; Phosphorus ; Chloride Channels/genetics* ; Vacuolar Proton-Translocating ATPases/genetics*

Cord Blood Stem Cell Transplantation ; adverse effects ; Graft vs Host Disease ; etiology ; Histocompatibility Testing ; Humans ; Infant ; Male ; Osteopetrosis ; etiology ; therapy ; Transplantation, Homologous

Autosomal dominant osteopetrosis (ADO) is a sclerotic bone disorder due to failure of osteoclasts. ADO poses difficulties during arthroplasty because of the increased chance for iatrogenic fractures due to sclerotic bone. ADO is divided into two types based on radiological findings, fracture risk, and osteoclast activity. These differences suggest less brittle bone in patients with ADO I compared to that of patients with ADO II, which suggests a smaller chance of preoperative fractures during cementless arthroplasty in ADO I compared with that in ADO II. A case of cementless total knee arthroplasty in a patient with ADO I is presented. Total hip arthroplasty was performed during follow-up, and known major problems related to ADO II were experienced. Therefore, the differences between ADO I and ADO II may not be clinically relevant for an iatrogenic fracture during arthroplasty in patients with ADO.
Acetabulum/injuries ; Adult ; Arthroplasty, Replacement, Knee/*adverse effects ; Down Syndrome/complications ; Female ; Femoral Fractures/etiology/surgery ; Genes, Dominant ; Humans ; Iatrogenic Disease ; Knee Joint/surgery ; Osteoarthritis, Knee/complications/*surgery ; Osteopetrosis/complications/*surgery ; Periprosthetic Fractures/*etiology/surgery ; Tibial Fractures/etiology/therapy

OBJECTIVEOsteopetrosis is a rare genetic disorder and the malignant infantile osteopetrosis (MIOP) is the worst subtype of this disease. Seventy percent of patients die in six years of life without proper treatment. Hematopoietic stem cell transplantation (HSCT) offers the only chance of cure for MIOP.

METHODRetrospective analysis was performed on 8 patients with MIOP who underwent HSCT in Beijing Children's Hospital during the period from 2006 to 2011.

RESULTEight cases (4 male and 4 female, mean age at HSCT 13.5 months) were diagnosed as malignant infantile osteopetrosis. Conditioning regimen included fludarabine, busulfan and cyclophosphamide. All patients received cyclosporin for prophylaxis of graft vs. host disease (GvHD). A UMD recipient underwent CD34(+) cell selection. ATG/ALG, mycophenolate mofetil (MMF) and methotrexate (MTX) used for recipients with unrelated cord donor (2) and recipients with haplo-identical donors (5). Average time for neutrophil engraftment was 15.7 day (9 - 36), platelet engraftment was 43.3 day (10 - 68). The patients were followed up from 47 days to 5 years, 1 patient died of post-transplant complications. Seven cases presented better in clinical manifestation. Acute GvHD I°-II° was observed in 6 patients, III°-IV° in 2 patients. It was controlled by anti-GvHD therapy.

CONCLUSIONNon-allogenic stem cell transplantation treatment of infantile MIOP showed high survival rate and restoration of hematopoiesis in haploid transplant patients, therefore, non-allogenic HSCT may be an option to treat MIOP in children.

Bone Marrow Transplantation ; adverse effects ; methods ; Child, Preschool ; Female ; Fetal Blood ; cytology ; Follow-Up Studies ; Genetic Predisposition to Disease ; Graft vs Host Disease ; drug therapy ; epidemiology ; prevention & control ; Haploidy ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Humans ; Infant ; Male ; Osteopetrosis ; mortality ; therapy ; Retrospective Studies ; Survival Analysis ; Transplantation Conditioning ; methods ; Transplantation, Homologous ; Treatment Outcome

Palpation of an abdominal mass in an infant or child presents a challenging problem in diagnosis and treatment. We reviewed the data on 166 patients under age 15 years who admitted to Ped. Dept. of PMC due to palpable abdominal mass in Jan. 1972-July 1977. The results are as follows 1. Of the 57 surgical cases, pathologically confirmed abdominal tumors were 39 cases. Of the 20 retroperitoneal tumors, Wilms tumors were 13 cases, neuroblastomas were 3 cases, polycystic kidney was 1 case, and retroperitoneal teratoma was 1 case. Of the 19 intraperitonel tumors, hepatomas were 3 cases, hepatoblastoma was 1 case, choledocal cysts were 3 cases, mesenteric and omental cysts were 4 cases, malignant lymphomas were 4 cases and ovarian cysts were 3 cases. Other surgical diseases were 2 cases of ascariasis and 2 cases of bezoar. 2. Medical cases were as follows : 35 cases of leukemia, 15 cases of infectious hepatitis, 14 cases of congenital syphilis 7 cases of liver cirrhosis 7 cases of lirerabscesses, 4 cases of miliary Tbc., 3 cases of congenital spherocytosis, 1 case of cryptococosis, I case of osteopetrosis and 1 case of erythroblastosis fetalis. 3. In age distribution, almost all cases(94%) of Wilms tumor and neuroblastoma were under age of 4 and half of medical cases in infancy were congenital syphilis. 4. Of the pathologically confirmed 39 abdominal tumors, 20 cases were retroperitoneal tumor and 19 cases were intraperitoneal tumor. Of the 20 retroperitonel tumor cases, 16 cases were renal origin, 3 cases were adrenal origin, and 1 case was teratoma. Of the 19 intraperitoneal tum orcases, 8 cases were hepatobiliary origin, 3 cases were ovary origin, 4 cases were omental and mesenteric origin and 4 cases were lymphatics origin. 5. Of the 39 abdominal tumor cases, 34 cases (87%) visited the hospital with the chief complaint of palpable abdominal mass. But, of the 94 medical cases, only 16 cases(17%) visited the hospital with the chief complaint of palpable abdominal mass. 6. In some cases presumptive diagnosis on the base of history taking, physical examination, chest X-ray, simple abdominal X-ray. Peripheral blood findings on admission were uncorrect. In 1 case of Wilms tumor, we suspected liver abscess on admission. In 1/3 case of intraperitoneal tumors, we suspected retroperitoneal tumor on admission. We suspected lymphoma on admission in 1 case of ascariasis and 1 case of bezoar. We misdiagnoed 1 case of miliary Tbc. As hepatoma, 1 case of liver cirrhosis as retroperitoneal tumor and 1 case of congenital syphilis as retroperitoneal tumor on admission. 7. In the treatment of malignant abdominal tumor, we tried all possible measures such as surgery, chemotherapy, and radiation therapy. But prognosis of all malignant abdominal tumors were very poor. Only 1 case of Wilms tumor and 1 case of hepatoblastoma were survived at the time of review.
Age Distribution ; Ascariasis ; Bezoars ; Carcinoma, Hepatocellular ; Child* ; Diagnosis ; Drug Therapy ; Erythroblastosis, Fetal ; Female ; Hepatitis A ; Hepatoblastoma ; Humans ; Infant* ; Infant, Newborn ; Leukemia ; Liver Abscess ; Liver Cirrhosis ; Lymphoma ; Neuroblastoma ; Osteopetrosis ; Ovarian Cysts ; Ovary ; Palpation ; Physical Examination ; Polycystic Kidney Diseases ; Prognosis ; Syphilis, Congenital ; Teratoma ; Thorax ; Wilms Tumor