Osteopetrosis, Autosomal Recessive 1 (OPTB1)

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Disease Ontology 12 DOID:0110942 OMIM® 57 259700 OMIM Phenotypic Series 57 PS259700 MeSH 44 D010022

MedGen 41 C1850127 SNOMED-CT via HPO 68 103276001 10629009 111253001 127034005 128613002 15188001 16294009 165397008 1926006 193093009 22640007 230745008 246545002 258211005 268029009 271737000 280816001 313307000 343087000 36440009 367489004 432788009 563001 60168000 65956007 74820003 76976005 80515008 80967001 84757009 90145001 91175000 95666008 95828007 more UMLS 70 C1318518 C1850127

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) (Updated 05-Apr-2021)

MalaCards based summary : Osteopetrosis, Autosomal Recessive 1, also known as autosomal recessive osteopetrosis 1, is related to autosomal recessive malignant osteopetrosis and osteopetrosis, autosomal recessive 5, 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), and among its related pathways/superpathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and PI3K-Akt signaling pathway. The drugs Levoleucovorin and leucovorin have been mentioned in the context of this disorder. Affiliated tissues include bone, bone marrow and spleen, and related phenotypes are macrocephaly and failure to thrive

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.

GARD : ²⁰ 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 : ⁷² 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 (Updated 05-Apr-2021)

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