combined oxidative phosphorylation defect type 15

Combined oxidative phosphorylation defect type 15 is a mitochondrial disorder that affects energy production in cells. It is caused by pathogenic variants in the MTFMT gene, which disrupt mitochondrial protein synthesis. The condition typically presents in infancy or early childhood and predominantly impacts the central nervous system, manifesting with developmental delays and motor difficulties. It is extremely rare, affecting fewer than 1 in 1,000,000 people.

Individuals with combined oxidative phosphorylation defect type 15 commonly present with progressive neurologic deterioration, global developmental delay, and characteristic laboratory findings such as decreased activity of mitochondrial complexes and increased lactate levels. Early features include muscular hypotonia, gait ataxia, and mild pyramidal tract signs. As the condition evolves, affected children may develop intellectual disability, visual impairments (such as reduced visual acuity and strabismus), and seizures, along with other variable findings like microcephaly, short stature, and cardiac conduction abnormalities. Not all individuals experience all features, and severity varies considerably.

Combined oxidative phosphorylation defect type 15 results from pathogenic variants in the MTFMT gene, which plays a critical role in the synthesis of proteins needed for mitochondrial energy production. This condition is inherited in an autosomal recessive pattern, meaning that an affected individual inherits two copies of the mutated gene, one from each parent. It is more common when parents share a common ancestor, as this increases the likelihood that both carry the same rare genetic variant. Genetic counseling is recommended to help families understand recurrence risks and options for family planning.

Currently, management focuses on supportive care and symptom management, as there are no treatments specifically approved for combined oxidative phosphorylation defect type 15. Treatment is individualized and typically involves a multidisciplinary team to address the wide range of symptoms. Approaches may include physical and occupational therapy to support motor development, interventions to manage seizures, and careful monitoring of cardiac and visual function. Regular surveillance is an essential part of long-term care, and genetic counseling is recommended to assist families in understanding the implications of the autosomal recessive inheritance pattern.

The prognosis for combined oxidative phosphorylation defect type 15 varies widely between individuals. With current standards of care, many individuals experience stabilization after initial developmental challenges, although some may later experience motor decline or persistent intellectual disability. Outcomes described in medical literature continue to evolve as standards of care improve, and severity and symptoms vary widely between individuals. Families often find it helpful to connect with specialists familiar with mitochondrial disorders and neurology to navigate ongoing management and care.