Background: StAR deficiency is a rare cause of primary adrenal insufficiency (PAI), with fewer than 100 cases reported worldwide. The first patients to be described suffered from severe forms of lipoid adrenal hyperplasia leading to severe undervirilization in 46,XY foetuses. More recently, however, less severe forms, known as "non-classical" or "atypical lipoid adrenal hyperplasia", presenting with PAI with salt wasting (SW) syndrome and normal male genitalia have been reported.
Objective: To present clinical and genetic data in five patients from three families with StAR deficiency.
Methods: Clinical data were collected from all known patients with StAR deficiency. Parental consent was obtained for genetic analysis to be performed. Massively parallel sequencing (MPS) with a custom panel targeting candidate genes in adrenal insufficiency was carried out. Mutations identified by MPS were confirmed in patients and their parents by Sanger sequencing.
Results: Between 2011 and 2018, five patients, current median (range) age 2.6 (0.6-7.4) years were found to have StAR deficiency. Clinical and genetic data are summarized in the table.
|Patient (Pt)||Pt1||Pt2||Pt3||Pt 4||Pt 5|
|Family history of adrenal insufficiency||Sister died at 2 months (SW)||Brother (Pt3)||Sister (Pt2)||Brother (Pt 5)||Sister (Pt4)|
|Age at presentation||23 days||5 months||1 day||19 months||24 months|
|Mode of presentation||SW||SW||Family history and DSD||SW|
|Length(cm) of cliterophallus|
|Sex of rearing||Female||Female||Male||Female||Male|
|Na/K (meq/l) at diagnosis||114/5.2||121/5.6||140/3.7||137/4.7 (on treatment)||126/6|
|StAR gene mutation|
|c.306+2dupT in intron 3||c.64+480_c.167del in exon 2||c.64+480_c.167del in exon 2||c.73T>A|
Discussion: StAR deficiency is a rare but important cause of PAI. Diagnosis in the classic form presenting with severe undervirlization requires investigation of chromosomal sex and the presence of a uterus. However, the existence of atypical forms with normal or mild undervirilization underlines the importance of testing for genes involved with steroidogenesis, including StAR, in unexplained PAI.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology