Non-classical lipoid adrenal hyperplasia presenting as hypoglycemic seizures

2020 ◽  
Vol 33 (11) ◽  
pp. 1507-1509
Author(s):  
Meenal Garg ◽  
Vasundhara Chugh ◽  
Sunil Dutt Sharma ◽  
Prashant Mitharwal ◽  
Ankit Mangla
Keyword(s):  
Adrenal Insufficiency ◽  
Regulatory Protein ◽  
Genetic Diagnosis ◽  
Reproductive Function ◽  
Adrenal Hyperplasia ◽  
Classical Form ◽  
Threatening Condition ◽  
Life Threatening ◽  
Steroidogenic Acute Regulatory ◽  
Star Gene

AbstractIntroductionPrimary adrenal insufficiency is a potentially life-threatening condition that can have many underlying causes. Mutations in the steroidogenic acute regulatory protein (StAR) gene produce lipoid congenital adrenal hyperplasia (LCAH) which usually presents in the infantile period with severe symptoms of adrenal insufficiency. Less commonly, a non-classical form is identified which may present at a later age in affected individuals. Till date, around 30 individuals with the non-classical form have been described.Case presentationWe describe a 4-year-old 46, XX Indian girl who presented with hypoglycemic seizures and was subsequently diagnosed as non-classical LCAH on genetic analysis, with homozygous R188C mutation in the StAR gene.ConclusionsStAR mutations may have a variety of clinical presentations and are likely under-diagnosed. Genetic diagnosis is important for treatment as well as monitoring of reproductive function.

scholarly journals A novel mutation of the StAR gene with congenital adrenal hyperplasia and its association with heterochromia iridis: a case report

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Vera Splittstösser ◽  
Felix Schreiner ◽  
Bettina Gohlke ◽  
Maik Welzel ◽  
Paul-Martin Holterhus ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Novel Mutation ◽  
Regulatory Protein ◽  
Homozygous Mutation ◽  
Elevated Concentration ◽  
Adrenal Hyperplasia ◽  
Heterochromia Iridis ◽  
Phenotypical Feature ◽  
Steroidogenic Acute Regulatory ◽  
Star Gene

Abstract Background We report a novel mutation within the StAR gene, causing congenital adrenal hyperplasia, with the so far unreported association with heterochromia iridis. Case presentation In 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. Conclusion 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.

scholarly journals Mechanism for the development of ovarian cysts in patients with congenital lipoid adrenal hyperplasia

2000 ◽  
pp. 274-279 ◽  
Author(s):  
M Shima ◽  
A Tanae ◽  
K Miki ◽  
N Katsumata ◽  
S Matsumoto ◽  
...  
Keyword(s):  
Body Temperature ◽  
Basal Body ◽  
Regulatory Protein ◽  
Ovarian Cysts ◽  
Adrenal Hyperplasia ◽  
Basal Body Temperature ◽  
Congenital Lipoid Adrenal Hyperplasia ◽  
Steroidogenic Acute Regulatory ◽  
Lh Releasing Hormone ◽  
Star Gene

OBJECTIVE: Although ovarian cysts commonly occur in patients with congenital lipoid adrenal hyperplasia (CLAH), the mechanism of development remains to be determined. To clarify the pathogenesis of the ovarian cysts, endocrinological examinations were performed in patients with CLAH. METHODS: The subjects were three Japanese CLAH patients. Basal body temperature, serum and urinary gonadotropin levels, serum and/or urinary ovarian hormones and mutations of the steroidogenic acute regulatory protein (StAR) gene were examined. RESULTS: The basal body temperature was not biphasic in any patient. Basal LH levels were high in all CLAH patients and markedly responded to LH-releasing hormone in two patients. Urinary gonadotropin analysis revealed repetitive LH surges in the menstrual cycles of the CLAH patients. No increase in the urinary pregnanediol suggested anovulation in all patients, and bilateral ovarian cysts were found in two of the subjects. Examination of the StAR gene revealed a frameshift mutation 840delA at codon 238, a nonsense mutation Q258X at codon 258, a homozygotic mutation at Q258X, and a compound heterozygotic mutation with 251insG and Q258X. CONCLUSIONS: We concluded that the development of ovarian cysts may be derived from continued anovulation in CLAH patients. Elevated LH levels may be explained by increased sensitivity of the anterior pituitary to circulating estrogen.

scholarly journals Congenital Lipoid Adrenal Hyperplasia Caused by a Novel Splicing Mutation in the Gene for the Steroidogenic Acute Regulatory Protein

2004 ◽  
Vol 89 (2) ◽  
pp. 946-951 ◽  
Author(s):  
Alexis A. González ◽  
M. Loreto Reyes ◽  
Cristian A. Carvajal ◽  
Jaime A. Tobar ◽  
Lorena M. Mosso ◽  
...  
Keyword(s):  
Regulatory Protein ◽  
Steroidogenic Acute Regulatory Protein ◽  
Wild Type ◽  
Adrenal Hyperplasia ◽  
Cos Cells ◽  
Star Protein ◽  
Congenital Lipoid Adrenal Hyperplasia ◽  
Intron 1 ◽  
Steroidogenic Acute Regulatory ◽  
Star Gene

Steroidogenic acute regulatory protein (StAR) plays a crucial role in the transport of cholesterol from the cytoplasm to the inner mitochondrial membrane, facilitating its conversion to pregnenolone by cytochrome P450scc. Its essential role in steroidogenesis was demonstrated after observing that StAR gene mutations gave rise to a potentially lethal disease named congenital lipoid adrenal hyperplasia, in which virtually no steroids are produced. We report here a 2-month-old female patient, karyotype 46XY, who presented with growth failure, convulsions, dehydration, hypoglycemia, hyponatremia, hypotension, and severe hyperpigmentation suggestive of adrenal insufficiency. Serum cortisol, 17OH-progesterone, dehydroepiandrosterone sulfate, testosterone, 17OH-pregnenolone, and aldosterone levels were undetectable in the presence of high ACTH and plasma renin activity levels. Immunohistochemical analysis of testis tissues revealed the absence of StAR protein. Molecular analysis of StAR gene demonstrated a homozygous G to T mutation within the splice donor site of exon 1 (IVS1 + 1G>T). Her parents and one brother were heterozygous for this mutation. In vitro analysis of the mutation was performed in COS cells transfected with minigenes coding regions spanning exon-intron 1 to 3 carrying the mutant and the wild-type sequences. RT-PCR analyses of the mutant gene showed an abnormal mRNA transcript of 2430 bp (normal size 433 bp). Sequence analysis of the mutant mRNA demonstrated the retention of intron 1. Immunolocalization of the StAR minigene product detected the peptide in the mitochondria of COS cells transfected with the wild-type minigene but not in those transfected with the mutant minigene. We conclude that this mutation gives rise to a truncated StAR protein, which lacks an important N-terminal region and the entire lipid transfer domain.

scholarly journals The rare form of congenital adrenal hyperplasia caused by an autosomal dominant form of STAR deficiency

2018 ◽  
Vol 64 (3) ◽  
pp. 157-159
Author(s):  
Natalia Y. Kalinchenko ◽  
Galina V. Chistousova ◽  
Vasily M. Petrov ◽  
Evgeny V. Vasiliev ◽  
Anatoly N. Tiulpakov
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adrenal Insufficiency ◽  
Autosomal Dominant ◽  
Regulatory Protein ◽  
Heterozygous Mutation ◽  
Adrenal Hyperplasia ◽  
Dominant Form ◽  
Recessive Mutations ◽  
Sex Development ◽  
Star Gene

The steroidogenic acute regulatory protein (StAR) is crucial for transport of cholesterol to mitochondria where biosynthesis of steroids is initiated. Loss of StAR function due to autosomal-recessive mutations in the STAR gene leads to lipoid congenital adrenal hyperplasia (LCAH) which is characterized by impaired synthesis of adrenal and gonadal steroids, which causes adrenal insufficiency, primary ovarian failure in 46XX patients, or 46XY disorder of sex development (DSD). However, there were a few reports of 46 XY DSD patients with LCAH caused by a heterozygous mutation in the STAR gene. Here, we describe another rare case of LCAH in a 46XY patient with DSD and primary adrenal insufficiency due to an autosomal-dominant mutation in the STAR gene.

Sign in / Sign up

Export Citation Format

Share Document