congenital lipoid adrenal hyperplasia due to STAR deficency

Congenital lipoid adrenal hyperplasia due to STAR deficency is one of the most severe forms of congenital adrenal hyperplasia, primarily affecting the adrenal glands and sex development. It results from pathogenic variants in the STAR gene, which plays a critical role in steroid hormone production. The condition is typically apparent early in life, with affected individuals presenting signs of adrenal insufficiency and, in some cases, sex reversal in genetic males. Prevalence information is not well established, and the condition is recognized as a serious endocrine disorder.

The clinical presentation of this condition reflects its multisystem involvement. The majority of affected individuals exhibit signs of adrenal insufficiency, such as vomiting, hyperkalemia, hyponatremia, and low cortisol levels, which lead to increased ACTH levels and resultant hyperpigmentation of the skin. In addition, there can be notable differences in sexual development, including female external genitalia in individuals with a 46,XY karyotype and, less frequently, male pseudohermaphroditism. Some patients may also experience abnormalities in the nervous system, with occasional reports of encephalopathy and seizures. That not all individuals experience all features, and severity varies considerably.

This condition is caused by pathogenic variants in the STAR gene, which is essential for the transport of cholesterol into mitochondria for steroid hormone synthesis. Disruption of STAR function results in severely reduced steroid production, leading to life‐threatening adrenal insufficiency and abnormal sexual development. The inheritance pattern is autosomal recessive, meaning that an affected individual has inherited two copies of the altered gene, one from each parent. Families with a history of consanguinity may have a higher likelihood of both parents carrying the same pathogenic variant, and genetic counseling is recommended to help understand the implications for future family planning.

Currently, management of congenital lipoid adrenal hyperplasia due to STAR deficency focuses on supportive care and symptom management. Since there are no FDA-approved treatments specifically linked to this condition, therapy is tailored to address adrenal insufficiency and its complications through hormone replacement and careful electrolyte management. A multidisciplinary approach involving endocrinologists and other specialists is critical, and regular surveillance is essential for monitoring potential complications. Patients are encouraged to discuss all available treatment options and management strategies with their healthcare team, and genetic counseling is recommended for families to understand the risks and implications of autosomal recessive inheritance.

The outlook for individuals with congenital lipoid adrenal hyperplasia due to STAR deficency is highly variable. With current standards of care, many individuals receive supportive management that can improve quality of life, although the severity of adrenal insufficiency and complications related to abnormal steroid production continue to pose significant challenges. Outcomes vary depending on the severity of symptoms, age at diagnosis, and access to specialized care. Given that modern management and ongoing healthcare improvements continue to evolve, patients and families are advised to seek genetic counseling and connect with specialist teams to better understand long-term expectations.

Clinical trials are underway exploring new treatment approaches for congenital lipoid adrenal hyperplasia due to STAR deficency. While current management is focused on supportive care, individuals interested in clinical trials can search ClinicalTrials.gov or consult their healthcare team regarding eligibility and emerging therapies.