sitosterolemia 1

Sitosterolemia 1 is an inherited metabolic condition affecting sterol transport that involves multiple body systems, particularly the hematologic and cardiovascular systems. It is caused by changes in the ABCG8 gene, which plays a key role in cholesterol and plant sterol regulation. The condition is inherited in an autosomal recessive pattern, meaning that it typically appears when an affected individual inherits two altered copies of the gene. The precise prevalence of sitosterolemia 1 is not well established, and affected individuals may present at varying ages.

Individuals with sitosterolemia 1 characteristically exhibit a distinct set of findings that include stomatocytosis, anemia, and reticulocytosis, along with corneal arcus, carotid artery stenosis, and the presence of giant platelets. Additional laboratory abnormalities, such as increased circulating lactate dehydrogenase concentration and reduced haptoglobin levels, are also invariably observed. Other notable features include splenomegaly, hypercholesterolemia, xanthelasma, thrombocytopenia, and coronary artery atherosclerosis. Not all individuals experience every feature, and severity varies widely between individuals.

Sitosterolemia 1 is caused by pathogenic variants in the ABCG8 gene, which is crucial for proper sterol transport and regulation. The condition is inherited in an autosomal recessive manner, meaning that both copies of the gene must be altered for the condition to manifest. This inheritance pattern implies that each child of parents who are both carriers has a 25% chance of being affected. Variability in the clinical presentation may occur even among affected individuals, and genetic counseling is valuable for families to understand the implications for future pregnancies.

Currently, management of sitosterolemia 1 focuses on supportive care and symptom management, as there are no FDA-approved treatments specifically for this condition. Treatment is tailored to the individual and typically involves a multidisciplinary team to address the various systemic manifestations. Given the complex nature of the condition, patients should discuss treatment options with their healthcare team to determine which therapies may be most appropriate. Genetic counseling is also recommended to help families understand inheritance patterns and explore their options.

The long-term outlook for individuals with sitosterolemia 1 varies based on the severity of symptoms, age at diagnosis, and access to specialized care. With current standards of care, many individuals are able to manage their symptoms effectively, although cardiovascular complications may develop over time. The condition may progress, stabilize, or show a variable course in different individuals, and outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with genetic counselors and specialists familiar with this condition.