Osteopetrosis, Autosomal Recessive 1 (OPTB1)

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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 08-Dec-2022)

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 inorganic cations/anions and amino acids/oligopeptides and Signaling by Receptor Tyrosine Kinases. The drug Levoleucovorin has been mentioned in the context of this disorder. Affiliated tissues include bone, bone marrow and spleen, and related phenotypes are macrocephaly and hydrocephalus

GARD: ¹⁹ 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 serious 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 pancytopenia. In rare cases, there may be neurological impairment or involvement of other body systems. Osteopetrosis may be caused by genetic changes in at least 10 genes. Inheritance can be autosomal recessive, autosomal dominant, or X-linked recessive with the most severe forms being autosomal recessive.

UniProtKB/Swiss-Prot: ⁷³ 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.

Disease Ontology: ¹¹ 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.

Clinical features from OMIM®:

Search NIH Clinical Center for Osteopetrosis, Autosomal Recessive 1