Endocrine Abstracts

JOINT3261

Background: Lipoid congenital adrenal hyperplasia (LCAH) is the most severe form of congenital adrenal hyperplasia. It is characterized by severe adrenal insufficiency and gonadal steroidogenesis impairment. Most cases of lipoid CAH are caused by recessive mutations in the gene encoding a steroidogenic acute regulatory protein (StAR).

Objectives: To identify variants of StAR and to describe the phenotype and genotype of patients with LCAH.

Patients and methods: This is a case series study of 10 cases from 9 unrelated families. The study included mutation analysis using whole exome sequencing or panel sequencing, description of clinical manifestations, karyotyping, and biochemistry tests.

Results: Seven of 10 cases have a female appearance. Among them, 4 have a karyotype of 46,XX, ovaries, and uterus on pelvic ultrasound; 3 have a karyotype of 46,XY and testis. 2 of 10 have a male-typical appearance and 46,XY, and testis. 1 of 10 has bilateral cryptorchidism, truth micropenis, hypoplasia of the scrotum, and 46,XY. Six of ten patients presented with severe adrenal insufficiency in early infancy (under 6 months old). Remain cases presented the first adrenal crisis from 15 months to 6.5 years of age. The investigations showed very high plasma ACTH levels (440–1551 pmol/l), and salt losing with hyponatremia (117–127 mmol/l) on admission, while the plasma 17OHP level was normal or decreased. All patients have good responses to glucocorticoid and mineral corticoid replacement therapy. Nine different pathogenic/like pathogenic variants in the StAR gene were identified including c.577C>T (p.R193X), c.649A>G (p.R217G), c.545G>A (p.R182H), c.562C>T (p.R188C), c.496A>T (p.I166F), c.11C>G (p.A4G), c.784del (p.Q262RfsX59), c.466ã€11T>A, and Del exon 1-3. Homozygous mutations were identified in 6 probands and compound heterozygous mutations were identified in 3 probands.

Conclusions: The phenotype of LCAH can be classic or non-classical form. The clinical manifestations include early/severe or later onset of adrenal insufficiency and female external genitalia or male-typical genitalia in 46, XY. Molecular testing using next-generation sequencing helps confirmation of the LCAH – a rare cause of adrenal insufficiency, with effective treatment and genetic counseling.