A rare cause of primary adrenal insufficiency due to a homozygous Arg188Cys mutation in the gene.

Burget, Lukas; Parera, Laura Audí; Fernandez-Cancio, Monica; Gräni, Rolf; Henzen, Christoph; Flück Pandey, Christa Emma (2018). A rare cause of primary adrenal insufficiency due to a homozygous Arg188Cys mutation in the gene. Endocrinology, diabetes & metabolism case reports, 2018(1) Bioscientifica 10.1530/EDM-18-0003

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[20520573 - Endocrinology, Diabetes & Metabolism Case Reports] A rare cause of primary adrenal insufficiency due to a homozygous Arg188Cys mutation in the STAR gene.pdf - Published Version
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Steroidogenic acute regulatory protein () is a key protein for the intracellular transport of cholesterol to the mitochondrium in endocrine organs (e.g. adrenal gland, ovaries, testes) and essential for the synthesis of all steroid hormones. Several mutations have been described and the clinical phenotype varies strongly and may be grouped into classic lipoid congenital adrenal hyperplasia (LCAH), in which all steroidogenesis is disrupted, and non-classic LCAH, which resembles familial glucocorticoid deficiency (FGD), which affects predominantly adrenal functions. Classic LCAH is characterized by early and potentially life-threatening manifestation of primary adrenal insufficiency (PAI) with electrolyte disturbances and 46,XY disorder of sex development (DSD) in males as well as lack of pubertal development in both sexes. Non-classic LCAH manifests usually later in life with PAI. Nevertheless, life-long follow-up of gonadal function is warranted. We describe a 26-year-old female patient who was diagnosed with PAI early in life without detailed diagnostic work-up. At the age of 14 months, she presented with hyperpigmentation, elevated ACTH and low cortisol levels. As her older brother was diagnosed with PAI two years earlier, she was put on hydrocortisone and fludrocortisone replacement therapy before an Addisonian crisis occurred. Upon review of her case in adulthood, consanguinity was noted in the family. Genetic analysis for PAI revealed a homozygous mutation in the gene (c.562C>T, p.Arg188Cys) in both siblings. This mutation has been previously described in non-classic LCAH. This case illustrates that early onset, familial PAI is likely due to autosomal recessive genetic mutations in known genes causing PAI.

Learning points

In childhood-onset PAI, a genetic cause is most likely, especially in families with consanguinity.Adult patients with an etiologically unsolved PAI should be reviewed repeatedly and genetic work-up should be considered.Knowing the exact genetic diagnosis in PAI is essential for genetic counselling and may allow disease-specific treatment.Young men and women with NCLAH due to homozygous Arg188Cys mutation should be investigated for their gonadal function as hypogonadism and infertility might occur during puberty or in early adulthood.

Item Type:

Journal Article (Further Contribution)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine

UniBE Contributor:

Flück Pandey, Christa Emma

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2052-0573

Publisher:

Bioscientifica

Language:

English

Submitter:

Christa Emma Flück Pandey

Date Deposited:

26 Feb 2019 14:12

Last Modified:

30 Oct 2019 19:15

Publisher DOI:

10.1530/EDM-18-0003

PubMed ID:

29576868

BORIS DOI:

10.7892/boris.123701

URI:

https://boris.unibe.ch/id/eprint/123701

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