Session: SUN 203-235-Steroid Hormone Actions, Biosynthesis and Metabolism (posters)
Bench to Bedside
Poster Board SUN 207
Congenital Lipoid Adrenal Hyperplasia is an extremely rare cause of CAH. Most cases are due to mutations in the steroidogenic acute regulatory protein (StAR), a mitochondrial phosphoprotein that mediates transport of cholesterol from the outer to the inner mitochondrial membranes. More than 35 inactivating mutations have been described in StAR. We describe 3 cases of CAH; two had previously known mutation and one has a novel mutation in StAR gene.
Patients and Methods:
We describe the clinical and genetic bases of 3 patients with CAH secondary to StAR mutations. Molecular testing was performed on genomic DNA isolated from peripheral leucocytes using PCR and direct Sanger sequencing of all exons and exon-intron boundaries of StAR gene. This was compared with normal sequence using Ensemble and NCBI databases. Testing for the same mutation in 200 normal subjects was done in the novel mutation.
Patient 1: A 13-year old girl born to consanguineous parents. She presented at 1 month of age with increasing pigmentation and hypotensive crisis. She had normal female external genitalia. She was treated with hydrocortisone and fludrocortisone and did well. Investigations: 46XY karyotype, ACTH >2000 ng/L, basal and stimulated cortisol, 11 deoxycortisol, 17 OH progesterone, 17-OH-pregnenolone, testosterone and aldosterone were undetectable. Renin was very high. Ultrasound of the pelvis showed undescended inguinal testes but no uterus or ovaries. She underwent gonadectomy and was raised as a female. Genetic testing revealed a previously described missense mutation (c.545G>A, p. 182R>H)
Patient 2: A 22-year old girl born to consanguineous parents. At 2 weeks of age, she presented with dark skin and hypotensive crisis. she had normal female external genitalia and palpable undescended testis. Investigations: ACTH 1253, undetectable cortisol, 11 dexoycortsiol and aldosterone but low normal 17OH progesterone. Ultrasound of the pelvis showed no evidence of internal female genitalia. She was treated with hydrocortisone and fludrocortisone and underwent gonadoectomy at age 5 years. Genetic testing revealed a novel nonsense mutation in exon 7 (c. 790C>T, p.264 Q>X) leading to stop codon and truncation of the gene.
Patient 3: A 7 year old with 46XY karyotype. She developed hypotensive crisis and skin pigmentation at 3 weeks of age. She had normal female external genitalia. Ultrasound of the pelvis showed no internal female genitalia. Inestigation: elevated ACTH (>1000 ng/L0, undetectable cortisol, 11 deoxycortsiol, aldosterone and testosterone. 17OH progesterone was very low. She was raised as a female. Genetic analysis revealed a previously described missense mutation (c.545G>A, p.182R>H).
Conclusions: StAR mutations lead to severe form of CAH. This report describes the clinical, biochemical and genetic bases of 3 cases with this extremely rare syndrome including a novel mutation.
Nothing to Disclose: DA, MA, EQ, ASA, BB, ASA
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