HSD10 mitochondrial disease

HSD10 mitochondrial disease is a rare, life-threatening neurometabolic condition that primarily affects the central nervous system and heart. It is caused by pathogenic variants in the HSD17B10 gene, which plays a critical role in mitochondrial metabolism. The condition is inherited in an X-linked pattern, and affected individuals, typically males, present with severe clinical findings at a young age. In terms of prevalence, this condition is very rare, affecting fewer than 1 in 1,000,000 people.

The clinical presentation of HSD10 mitochondrial disease is dominated by neurological involvement. Intellectual disability is universally reported, and affected individuals may also show progressive neurologic deterioration. In many cases, after a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills, followed by stabilization or further decline. Additionally, laboratory studies may reveal consistently elevated levels of circulating tiglylglycine. Not all individuals experience every feature, and severity varies considerably.

HSD10 mitochondrial disease is caused by pathogenic variants in the HSD17B10 gene, which encodes an enzyme essential for proper mitochondrial function. This condition is inherited in an X-linked pattern, which means that males are typically more severely affected, while females may also experience symptoms due to variable X-inactivation. Genetic counseling is recommended to help families understand the implications of this inheritance pattern and to discuss potential risks for future offspring.

Currently, management focuses on supportive care and symptom management, as there are no FDA-approved treatments specifically linked to HSD10 mitochondrial disease. Treatment is individually tailored and typically involves a multidisciplinary team to address the evolving needs associated with neurological and systemic manifestations. Regular surveillance is an essential part of long-term care, allowing for the early identification of complications. Patients should discuss treatment options with their healthcare team, and genetic counseling is recommended for those with this inherited condition.

The prognosis for individuals with HSD10 mitochondrial disease varies widely and depends on factors such as the age at diagnosis and access to specialized care. Some individuals experience a period of relative stability following early developmental challenges, while others may encounter gradual motor decline over the years. Life expectancy generally spans a broad range, and outcomes tend to improve as modern treatments and supportive therapies evolve. Outcomes described in medical literature continue to evolve as standards of care improve. It is important for families to work with specialists and seek guidance from genetic counselors as well as connect with support groups to help navigate future care and planning.