Osteopetrosis, Autosomal Recessive 1 (OPTB1)

External Ids:

OMIM 57 259700 Disease Ontology 12 DOID:0110942 MedGen 42 C1850127

MeSH 44 D010022 SNOMED-CT via HPO 69 258211005 230745008 103276001 15188001 343087000 95828007 65956007 563001 76976005 80967001 128613002 246545002 313307000 84757009 91175000 10629009 36440009 432788009 16294009 127034005 165397008 271737000 90145001 80515008 111253001 60168000 22640007 268029009 74820003 280816001 95666008 193093009 1926006 367489004 more UMLS 73 C1850127 C1318518

OMIM : ⁵⁷ Osteopetrosis (OPT) is a life-threatening disease caused by subnormal osteoclast function, with an incidence of 1 in 250,000 births. The disease usually manifests in the first few months of life with macrocephaly and frontal bossing, resulting in a characteristic facial appearance. Defective bone remodeling of the skull results in choanal stenosis with concomitant respiratory problems and feeding difficulties, which are the first clinical manifestation of disease. The expanding bone encroaches on neural foramina, leading to blindness, deafness, and facial palsy. Complete visual loss invariably occurs in all untreated patients, and hearing loss is estimated to affect 78% of patients with OPT. Tooth eruption defects and severe dental caries are common. Calcium feedback hemostasis is impaired, and children with OPT are at risk of developing hypocalcemia with attendant tetanic seizures and secondary hyperparathyroidism. The most severe complication of OPT, limiting survival, is bone marrow insufficiency. The abnormal expansion of cortical and trabecular bone physically limits the availability of medullary space for hematopoietic activity, leading to life-threatening cytopenia and secondary expansion of extramedullary hematopoiesis at sites such as the liver and spleen (summary by Aker et al., 2012). (259700)

MalaCards based summary : Osteopetrosis, Autosomal Recessive 1, also known as optb1, is related to osteopetrosis, autosomal recessive 5 and autosomal recessive malignant osteopetrosis, and has symptoms including ophthalmoplegia An important gene associated with Osteopetrosis, Autosomal Recessive 1 is TCIRG1 (T Cell Immune Regulator 1, ATPase H+ Transporting V0 Subunit A3). Affiliated tissues include bone, bone marrow and liver, and related phenotypes are macrocephaly and frontal bossing

Disease Ontology : ¹² An osteopetrosis characterized by autosomal recessive inheritance that has material basis in homozygous or compound heterozygous mutation in the TCIRG1 gene on chromosome 11q13.2.

NIH Rare Diseases : ⁵³ Osteopetrosis refers to a group of rare, inherited skeletal disorders characterized by increased bone density and abnormal bone growth. Symptoms and severity can vary greatly, ranging from neonatal onset with life-threatening complications (such as bone marrow failure) to the incidental finding of osteopetrosis on X-ray. Depending on severity and age of onset, features may include fractures, short stature, compressive neuropathies (pressure on the nerves), hypocalcemia with attendant tetanic seizures, and life-threatening pancytopenia. In rare cases, there may be neurological impairment or involvement of other body systems. Osteopetrosis may be caused by mutations in at least 10 genes. Inheritance can be autosomal recessive, autosomal dominant, or X-linked recessive with the most severe forms being autosomal recessive. Management depends on the specific symptoms and severity and may include vitamin D supplements, various medications, and/or surgery. Adult osteopetrosis requires no treatment by itself, but complications may require intervention.

UniProtKB/Swiss-Prot : ⁷⁵ Osteopetrosis, autosomal recessive 1: A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves.

Clinical features from OMIM:

259700

Search Clinical Trials , NIH Clinical Center for Osteopetrosis, Autosomal Recessive 1

Search GEO for disease gene expression data for Osteopetrosis, Autosomal Recessive 1.