ESPE Abstracts (2019) 92 P1-296

Three Novel Mutations of the StAR Gene in Five Algerian Patients Presenting with Classical and Non-Classical Lipoid Adrenal Hyperplasia

Asmahane Ladjouze1, Delphine Mallet2, Mohamed Demdoum3, Zair Bouzerar1, Yves Morel2, Florence Roucher-Boulez2


1Department of Paediatrics, CHU Bab El Oued, Algiers, Algeria. 2Service de Biochimie et Biologie Moléculaire Grand-Est, Hospices Civils de Lyon, Lyon, France. 3Paediatrics office, El Oued, Algeria


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)Pt1Pt2Pt3Pt 4Pt 5
ConsanguinityYesYesYesYesYes
Family history of adrenal insufficiencySister died at 2 months (SW)Brother (Pt3)Sister (Pt2)Brother (Pt 5)Sister (Pt4)
Age at presentation23 days5 months1 day19 months24 months
Mode of presentationSWSWFamily history and DSDSW
Pigmentation
SW
Micropenis
External genitaliaFemaleFemaleAmbiguousFemaleMale
Micropenis
Length(cm) of cliterophallus
Testes
Uterus
<0.5
Inguinal folds
No
<0.5
No
Yes
1
Inguinal folds
No
<0.5
No
Yes
1
Scrotal
No
Karyotype46,XY46,XX46,XYNDND
Sex of rearingFemaleFemaleMaleFemaleMale
Na/K (meq/l) at diagnosis114/5.2121/5.6140/3.7137/4.7 (on treatment)126/6
ACTH (pg/ml)140367738720002090
Renin (pg/ml)76.8863425171180
Testosterone (nmol/l)<0.050.41
AMH (pmol/l)359-209
StAR gene mutation
(homozygous)
c.306+2dupT in intron 3c.64+480_c.167del in exon 2c.64+480_c.167del in exon 2c.73T>A
p.Leu8Gln
c.73T>A
p.Leu8Gln

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.

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