Clinical and gene mutational characteristics of congenital lipid adrenal hyperplasia： case report and literature review

Objective To investigate clinical and molecular genetic characteristics of congenital lipid adrenal hyperplasia （CLAH） caused by steroidogenic acute regulatory protein （StAR） gene mutation.

Methods Clinical data of a CLAH patient admitted to Guangdong Women and Children Hospital in January 2020 were analyzed retrospectively, and high throughput and Sanger sequencing were used for gene analysis. A systematic search was conducted through Wanfang database, China National Knowledge Infrastructure and PubMed from January 1^st, 2000 to December 31^st, 2020. Literature of CLAH caused by StAR gene mutation were collected and analyzed.

Results In this case, the child developed repeated vomiting, skin pigmentation and other symptoms at 4 months old. Laboratory examination found low level of hypoblood sodium, hyperblood potassium, and significantly low level of steroid hormones such as cortisol, 17-hydroxyprogesterone, androenedisterone, testosterone, and progesterone. The adrenal CT showed bilateral normal adrenal structure didn’t exist. Genetic Test found compound heterozygous mutation of StAR C > T （c. 7 Q 258 X） > T （p.Q77X）. Parents confirmed that the two mutations were inherited, and the child was diagnosed as CLAH caused by StAR gene mutation. After glucocorticoid and mineralocorticoid replacement therapy, his symptoms gradually disappeared with normal growth and development at 1 year old follow up. After literature search, 10 Chinese and 4 English papers were found , and 32 cases of CLAH were reported together with this case.Most children with CLAH developed symptoms at infancy through comprehensive analysis. They usually had skin pigmentation, vomiting and growth retardation, and their gender was female. Laboratory tests indicated that most children had hyponatraemia, hyperkalemia, and low level of steroid hormones such as cortisol, 17-hydroxyprogesterone, androstenedione, testosterone and other steroids.Their growth and development were normal after glucocorticoid and mineralocorticoid replacement therapy. The common site of StAR gene mutation was c.772C > T（p.Q258X）.

Conclusion CLAH is a rare type of congenital adrenocortical hyperplasia. The onset of the illness is usually at infancy. It often manifests as skin pigmentation, water and electrolyte disorders, and feminization of the vulva. Timely and appropriate hormone replacement therapy can improve their clinical symptoms and prognosis. Genetic testing contributes to the diagnosis of CLAH. The p.Q258X mutation may be a hot-spot mutation in the StAR gene in the Chinese population.