autosomal recessive osteopetrosis 6

Autosomal recessive osteopetrosis 6 is a hereditary skeletal condition in which bones become abnormally dense yet fragile, leading to a unique combination of hardness and brittleness. It is caused by disease-causing changes in the PLEKHM1 gene, which interferes with the normal breakdown and remodeling of bone. Symptoms often appear in infancy or childhood and can affect individuals of any sex. Precise prevalence figures are not available, but reported cases suggest the disorder is uncommon worldwide. Severity and symptoms vary widely between individuals, even among siblings who share the same genetic change.

Dense bones that fracture easily are the hallmark of this condition. Early clues often include fractures after minimal trauma or X-rays that reveal markedly increased bone density, a sandwich-like appearance of the vertebral bodies, or an Erlenmeyer flask shape at the ends of the femurs. As children grow, they may experience recurrent fractures, back pain, and generalized bone pain because the overly thick bone cannot absorb routine stresses. Some individuals develop cortical sclerosis of the skull base or pelvis, which can compress nearby structures and contribute to discomfort. Because the bone marrow space is narrowed, a subset of people develop anemia or other blood cell shortages. Less commonly, nerve compression within narrowed bony canals can lead to neurological symptoms such as vision or hearing changes. Not all individuals experience all features, and the clinical spectrum ranges from mild fractures managed with simple casting to more complex disease requiring frequent medical attention.

PLEKHM1 provides instructions for a protein that helps osteoclasts—cells responsible for breaking down old bone—carry out their function. Pathogenic variants in both copies of the gene disrupt this process, so bone is formed but not properly resorbed, leading to the characteristic dense yet brittle skeleton. The condition is inherited in an autosomal recessive pattern, meaning an affected child receives one altered copy of PLEKHM1 from each parent. Parents, who usually have no symptoms, are called carriers. When both are carriers, each pregnancy has a twenty-five percent chance of producing a child with the condition, a fifty percent chance of producing a carrier, and a twenty-five percent chance of producing a child who is neither affected nor a carrier. The disorder is more likely to appear in families where parents share common ancestors because they are more likely to carry the same rare variant. Families often find it helpful to meet with a genetic counselor to discuss carrier testing, implications for other relatives, and options for future family planning.

Currently, management focuses on supportive care and symptom management, tailored to each person’s needs. Acute issues such as fractures are treated with standard orthopedic approaches, while persistent bone pain may be addressed through pain management strategies and physical therapy aimed at maintaining mobility and muscle strength. Long-term management includes regular surveillance for potential complications. This monitoring typically involves periodic imaging to assess bone architecture, blood counts to detect early marrow compromise, and neurological evaluation when there are signs of nerve compression. Care is best coordinated by a multidisciplinary team that may include orthopedic surgeons, endocrinologists, hematologists, neurologists, and physical therapists. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Genetic counseling provides additional support by clarifying inheritance and connecting families with appropriate specialists and community resources.

Outcomes for autosomal recessive osteopetrosis 6 vary depending on fracture frequency, the degree of bone-marrow involvement, and access to specialized care. Many individuals lead active lives with appropriate orthopedic management and ongoing monitoring, while others experience repeated fractures or complications that limit mobility. Because treatment strategies and supportive care continue to improve, outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with osteopetrosis and with genetic counselors who can guide long-term planning and provide up-to-date information on emerging care strategies.