Abstract
BackgroundWe report a novel mutation within the StAR gene, causing congenital adrenal hyperplasia, with the so far unreported association with heterochromia iridis.Case presentationIn a now 15-year-old girl (born at 41 + 6 weeks of gestation) adrenal failure was diagnosed in the neonatal period based on the clinical picture with spontaneous hypoglycaemia, hyponatremia and an extremely elevated concentration of ACTH (3381 pmol/l; ref. level 1,1–10,1 pmol/l), elevated renin (836 ng/l; ref. level 5–308 ng/l), and a decreased concentration of aldosterone (410 pmol/l; ref. level 886–3540 pmol/l). In addition to hyperpigmented skin the patient exhibited sectorial heterochromia iridis. Sequence analysis of the steroidogenic acute regulatory protein (StAR) gene showed a novel homozygous mutation (c.652G > A (p.Ala218Thr), which was predicted in-silico to be possibly damaging. Under daily steroid substitution her electrolyte levels are balanced while she became obese. Puberty occurred spontaneously.ConclusionA novel mutation in the StAR gene was identified in a patient with severe adrenal hypoplasia and sectorial heterochromia iridis. We discuss a causal relationship between these two rare phenotypes, i.e. whether very high levels of ACTH and alpha-MSH during early development might have disturbed early differentiation and distribution of uveal melanocytes. If confirmed in additional cases, discolorization of the iris might be considered as an additional phenotypical feature in the differential diagnosis of congenital adrenal insufficiency.
Highlights
We report a novel mutation within the steroidogenic acute regulatory protein (StAR) gene, causing congenital adrenal hyperplasia, with the so far unreported association with heterochromia iridis.Case presentation: In a 15-year-old girl adrenal failure was diagnosed in the neonatal period based on the clinical picture with spontaneous hypoglycaemia, hyponatremia and an extremely elevated concentration of Adrenocorticotropic hormone (ACTH) (3381 pmol/l; ref. level 1,1–10,1 pmol/l), elevated renin (836 ng/l; ref. level 5–308 ng/l), and a decreased concentration of aldosterone (410 pmol/l; ref. level 886–3540 pmol/l)
Loss of StAR function is characterized by impaired synthesis of adrenal and gonadal steroids, causing adrenal insufficiency, disorder of sex development (DSD) and in some cases failure of pubertal development
Partial loss of StAR activity may cause the phenotypical picture of lipoid congenital adrenal hyperplasia (LCAH) or isolated adrenal insufficiency [1,2,3,4,5]
Summary
A novel mutation in the StAR gene was identified in a patient with severe adrenal hypoplasia and sectorial heterochromia iridis. We discuss a causal relationship between these two rare phenotypes, i.e. whether very high levels of ACTH and alpha-MSH during early development might have disturbed early differentiation and distribution of uveal melanocytes. If confirmed in additional cases, discolorization of the iris might be considered as an additional phenotypical feature in the differential diagnosis of congenital adrenal insufficiency
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