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Pediatric Blood & Cancer Mar 2021Malignant infantile osteopetrosis (MIOP) is a rare hereditary disorder characterized by excessive bone overgrowth due to a defect in bone marrow resorption by... (Review)
Review
Malignant infantile osteopetrosis (MIOP) is a rare hereditary disorder characterized by excessive bone overgrowth due to a defect in bone marrow resorption by osteoclasts. In most cases, hematopoietic stem cell transplantation (HSCT) may correct bone metabolism but the rapidly progressing nature of this condition necessitates early diagnosis and prompt treatment to minimize irreversible cranial nerve damage. The management of patients with MIOP presents many unique challenges. In this review, the clinical management of patients with MIOP is discussed, including diagnosis, preparation for HSCT and special transplant considerations, management of unique HSCT complications, and long-term follow-up.
Topics: Bone Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Infant; Osteopetrosis; Prognosis
PubMed: 33314591
DOI: 10.1002/pbc.28841 -
Bone Nov 2022The osteopetroses reflect alterations of a special cell type, the osteoclast, belonging to the myeloid lineage. We have known this since the 1970s, confirmed by a myriad... (Review)
Review
The osteopetroses reflect alterations of a special cell type, the osteoclast, belonging to the myeloid lineage. We have known this since the 1970s, confirmed by a myriad of reports featuring details that guided subsequent molecular diagnosis and treatment. This review is a tribute to two pioneers in the field: Donald G. Walker PhD (1925-1979) and Sandy C. Marks Jr. PhD (1937-2002), who explored osteopetrosis pathophysiology and treatment. Using spontaneous mutant models of osteopetrosis in mice, rats, and rabbits, they demonstrated the cellular basis of osteopetrosis while also advancing understanding of the hematological origin of osteoclasts. This became the foundation for life-saving treatment by hematopoietic stem cell transplantation. Their prose was uncomplicated, experiments were straightforward, and conclusions were based on facts explaining why their teaching became influential worldwide. I never met Dr. Walker but spoke with Dr. Marks on several occasions. Both inspired my work and, now appreciating how they shaped the osteoclast/osteopetrosis scientist community, we must thank these eminent scientists for being mentors of all of us.
Topics: Animals; Bone Marrow; Hematopoietic Stem Cell Transplantation; Humans; Mice; Osteoclasts; Osteopetrosis; Population Health; Rabbits; Rats
PubMed: 35933094
DOI: 10.1016/j.bone.2022.116512 -
The Indian Journal of Medical Research Jan 2022
Topics: Humans; Osteomyelitis; Osteopetrosis
PubMed: 35859433
DOI: 10.4103/ijmr.IJMR_2340_20 -
The New England Journal of Medicine Sep 2022
Topics: Genes, Dominant; Humans; Osteopetrosis; Pedigree
PubMed: 36155625
DOI: 10.1056/NEJMicm2202055 -
Clinical Orthopaedics and Related... Sep 1993Autosomal dominant osteopetrosis is radiographically characterized by universal osteosclerosis, primarily involving the axial skeleton, and by symmetrical affections of... (Review)
Review
Autosomal dominant osteopetrosis is radiographically characterized by universal osteosclerosis, primarily involving the axial skeleton, and by symmetrical affections of the long bones without modeling defects. Based on standard radiographs, it is possible to describe two different subtypes with different clinical, biochemical, and histologic manifestations. Type I is radiographically characterized by pronounced osteosclerosis of the cranial vault, whereas Type II has end-plate thickening of the vertebrae (Rugger-Jersey spine) and endobones in the pelvis. Both types are strictly family related and seen in childhood. Combined radiogrammetric, biochemical, and histologic investigations indicate states of defective bone resorption, whereas bone formation seems to be normal in both types of patients. Patients with autosomal dominant osteopetrosis are often asymptomatic, and the diagnosis may be reached by chance. However, by systematic investigations, nearly all patients have manifestations related to the disorder. Symptoms are progressive with age, and correlated with osteosclerosis. The fracture frequency is increased in Type II patients, and normal in Type I, where biomechanical investigations have shown normal, or even increased trabecular bone strength. Treatment has been symptomatic. A rational treatment consists of stimulation of bone resorption, in combination with inhibition of bone formation if possible.
Topics: Bone Resorption; Chromosome Aberrations; Chromosome Disorders; Female; Fractures, Spontaneous; Genes, Dominant; Humans; Male; Osteopetrosis; Radiography
PubMed: 8358946
DOI: No ID Found -
Mymensingh Medical Journal : MMJ Oct 2011A 15 years old Bangladeshi boy presented with hepatosplenomegaly, anaemia, multiple fractures (symptomatic and asymptomatic) without jaundice was investigated....
A 15 years old Bangladeshi boy presented with hepatosplenomegaly, anaemia, multiple fractures (symptomatic and asymptomatic) without jaundice was investigated. Laboratory findings revealed leukoerythroblastic blood picture with reduced haemoglobin (7.7 gm/dl). Skeletal survey showed generalized increased bone density, sclerosed medulary space, Rugger-Jersey spine and diploic space filled with dense materials. Overlapping clinical features of both intermediate autosomal recessive and adult autosomal dominant variety of osteopetrosis were found in this patient but diagnosis were made on the basis of typical radiological finding which was mostly consistent with the adult autosomal dominant variety. The patient was treated conservatively and specialist consultation was taken in managing bony abnormalities. This patient was discharged with advised of subsequent follow-up.
Topics: Adolescent; Humans; Male; Osteopetrosis
PubMed: 22081195
DOI: No ID Found -
Genes Oct 2022Osteopetrosis (from the Greek "osteo": bone; "petrosis": stone) is a clinically and genetically heterogeneous group of rare diseases of the skeleton, sharing the same... (Review)
Review
Osteopetrosis (from the Greek "osteo": bone; "petrosis": stone) is a clinically and genetically heterogeneous group of rare diseases of the skeleton, sharing the same main characteristic of an abnormally increased bone density. Dense bones in radiological studies are considered the hallmark of these diseases, and the reason for the common term used: "Marble bone disease". Interestingly, a radiologist, Dr. Albers-Schonberg, described this disease for the first time in Germany in 1904. Indeed, radiology has a key role in the clinical diagnosis of osteopetrosis and is fundamental in assessing the disease severity and complications, as well as in follow-up controls and the evaluation of the response to treatment. Osteopetrosis includes a broad spectrum of genetic mutations with very different clinical symptoms, age onset, and prognosis (from mild to severe). This diversity translates into different imaging patterns related to specific mutations, and different disease severity. The main recognized types of osteopetrosis are the infantile malignant forms with autosomal recessive transmission (ARO-including the rarer X-linked recessive form); the intermediate autosomal recessive form (IAO); and the autosomal dominant ones ADO, type I, and type II, the latter being called 'Albers-Schonberg' disease. Imaging features may change among those distinct types with different patterns, severities, skeletal segment involvement, and speeds of progression. There are several classical and well-recognized radiological features related to osteopetrosis: increased bone density (all types with different degrees of severity assuming a 'Marble Bone Appearance' especially in the ARO type), different metaphyseal alterations/enlargement including the so-called 'Erlenmeyer flask deformity' (particularly of femoral bones, more frequent in ADO type 2, and less frequent in ARO and IAO), 'bone in bone' appearance (more frequent in ADO type 2, less frequent in ARO and IAO), and 'rugger-jersey spine' appearance (typical of ADO type 2). After conducting an overview of the epidemiological and clinical characteristic of the disease, this review article aims at summarizing the main radiological features found in different forms of osteopetrosis together with their inheritance pattern.
Topics: Humans; Osteopetrosis; Genes, Dominant; Inheritance Patterns; Radiology; Calcium Carbonate
PubMed: 36360203
DOI: 10.3390/genes13111965 -
Journal of Pediatric Hematology/oncology Apr 2018
Topics: Female; Hematopoietic Stem Cell Transplantation; Humans; Infant; Osteopetrosis; Vacuolar Proton-Translocating ATPases
PubMed: 29462001
DOI: 10.1097/MPH.0000000000001108 -
Revista Chilena de Pediatria Aug 2019Malignant Infantile Osteopetrosis (MIOP) is a rare and severe genetic disorder due to abnormal osteoclast activity.
INTRODUCTION
Malignant Infantile Osteopetrosis (MIOP) is a rare and severe genetic disorder due to abnormal osteoclast activity.
OBJECTIVE
To report an infant who presented Malignant Infantile Osteopetrosis, reviewing the most relevant diagnostic and therapeutic aspects.
CLINICAL CASE
A ten- month-old male infant with diagnosis of MIOP confirmed after presenting thrombocytopenia and visceromegaly. He was the first child of non-consanguineous parents, and among the findings, he presented severe hepatosplenomegaly, thrombocytopenia, and anemia; visual and hearing impair ment, and repeated infections. The diagnosis was confirmed by genetic study, which identified two heterozygous mutations in the TCIRG1 gene. Hematopoietic stem cells were transplanted without hematological recovery. The patient died due to occlusive venous disease.
DISCUSSION
MIOP is a rare, severe, and early-onset disease, with a high rate of suspicion necessary in the presence of hepa- tosplenomegaly and bone marrow failure. Early diagnosis and hematopoietic stem cells transplanta tion are the only potentially therapeutic interventions of this lethal entity.
Topics: Fatal Outcome; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Mutation; Osteopetrosis; Vacuolar Proton-Translocating ATPases
PubMed: 31859718
DOI: 10.32641/rchped.v90i4.987 -
Kathmandu University Medical Journal... 2022Osteopetrosis (Marble bone disease) is a very rare congenital genetic disease of skeleton, resulting from defective bone resorption, due to functionally defective...
Osteopetrosis (Marble bone disease) is a very rare congenital genetic disease of skeleton, resulting from defective bone resorption, due to functionally defective osteoclast, leading to accumulation of excessive bone mass. Malignant infantile osteopetrosis (MIO) is one of the varieties of osteopetrosis, which is fatal and is diagnosed in early infancy. Malignant infantile osteopetrosis is present with abnormal bone remodeling, hematological abnormities, features of extramedullary hematopoiesis. Radiology is the key of diagnosis. In this case, we present a 5-monthold male infant diagnosed as malignant infantile osteopetrosis, who presented with bronchopneumonia, anemia, thrombocytopenia, hepatosplenomegaly, failure to thrive (FTT).
Topics: Infant; Humans; Male; Child, Preschool; Osteopetrosis; Bone Marrow; Splenomegaly; Radiography; Anemia
PubMed: 36273302
DOI: No ID Found