Alu Sx repeat-induced homozygous deletion of the StAR gene causes lipoid congenital adrenal hyperplasia

2012 ◽  
Vol 130 (1-2) ◽  
pp. 1-6 ◽  
Author(s):  
Antje Eiden-Plach ◽  
Huy-Hoang Nguyen ◽  
Ursula Schneider ◽  
Michaela F. Hartmann ◽  
Rita Bernhardt ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Homozygous Deletion ◽  
Adrenal Hyperplasia ◽  
Star Gene

scholarly journals Novel STAR gene variant in a patient with classic lipoid congenital adrenal hyperplasia and combined pituitary hormone deficiency

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Moritake Higa ◽  
Akiko Zaha ◽  
Akiko Takushi ◽  
Nami Morishima ◽  
Toyofumi Majikina ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Adrenal Hyperplasia ◽  
Pituitary Hormone Deficiency ◽  
Combined Pituitary Hormone Deficiency ◽  
Pathogenic Variants ◽  
First Case ◽  
Novel Variant ◽  
Star Gene

AbstractWe report the first case of classic lipoid congenital adrenal hyperplasia and combined pituitary hormone deficiency. We identified pathogenic variants in the STAR gene: a novel variant of c.126_127delCCinsG, namely, p.Thr44Profs*2 and an already reported variant of c.634C>T, namely, p.Gln212*. The association with combined pituitary hormone deficiency might be just a coincidence.

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 A novel mutation in CYP17A1 gene leads to congenital adrenal hyperplasia: A case report

2019 ◽  
Author(s):  
Majid Nazari ◽  
Mohammad Yahya Vahidi Mehrjardi ◽  
Nosrat Neghab ◽  
Mahdi Aghabagheri ◽  
Nasrin Ghasemi
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Novel Mutation ◽  
Autosomal Recessive Disorder ◽  
Homozygous Deletion ◽  
Blood Levels ◽  
Primary Amenorrhea ◽  
Adrenal Hyperplasia ◽  
Lyase Deficiency

Background: Congenital adrenal hyperplasia is a rare autosomal recessive disorder where the mutation in P450 family 17 subfamily A member 1 gene (CYP17A1) is involved in its etiology. The disorder represents itself with low blood levels of estrogens, androgens, and cortisol that generally couples with hypertension, Hypokalemia, sexual primary amenorrhea, infantilism and in affected individuals. Case: In this study, the CYP17A1 gene in a 14-year-old female was examined. The karyotype of the patient was 46, XX, and the analysis of the CYP17A1 gene by Sanger sequencing revealed a novel homozygous deletion c.1052-1054CCT which led to isolated 17,20-lyase deficiency. Conclusion: In conclusion, this study report an in-frame deletion which results in isolated 17, 20-lyase deficiency, and the mutation might be used for diagnosis in other patients with distinctive clinical symptoms.

scholarly journals Novel StAR Gene Mutation Identified in a Moroccan Patient with Lipoid Congenital Adrenal Hyperplasia

2019 ◽  
Vol 1 (2) ◽  
pp. 19
Author(s):  
Zaddouq Hanane ◽  
Althel Pharel Opoko ◽  
Khadija Belhassan ◽  
Intissar Haddiya ◽  
Ahmed Gaouzi
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Early Stage ◽  
Regulatory Gene ◽  
Testicular Atrophy ◽  
Biological Assessment ◽  
Adrenal Hyperplasia ◽  
Sexual Hormones ◽  
Hydroxylase Deficiency ◽  
21 Hydroxylase Deficiency ◽  
Star Gene

Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive condition  that results from the deficiency of one of the steroidogenesis enzymes responsible for cortisol biosynthesis. In the majority of cases, CAH is caused by   21-hydroxylase deficiency. More rarely, the deficiency concerns  11b-hydroxylase, 3b-hydroxysteroid dehydrogenase, 17hydroxylase, or exceptionally StAR and P450 oxydoreductase. Here, we report the case of a 3 year and 4 months old male child,  born from a consanguineous marriage who presented at 15 months old with the salt-loss syndrome. Physical examination found generalized melanoderma, micropenis and bilateral cryptorchidism. Biological assessment at the time of diagnosis revealed hyponatremia, hyperkalemia, functional renal failure, hypoglycemia, low blood cortisol level, and high blood level of ACTH,  suggesting primary adrenal insufficiency. The patient presented  also with the abnormality of sexual differentiation with a 46 XY karyotype, testosteronemia level was low at the baseline and after HCG stimulation, pelvic ultrasound and MRI showed bilateral testicular atrophy in the inguinal position. The genetic study revealed a likely pathogenic homozygous variant in the StAR (steroidogenic acute regulatory) gene. Therapeutically, our patient was hydrated by saline solution and treated with hydrocortisone and fludrocortisone, then benefited from a surgical testicular correction marked by a favorable evolution. Although mutations in StAR gene are rare, they can be responsible for the defect in the early stage of steroidogenesis and therefore cause a deficiency in adrenal and sexual hormones biosynthesis.

scholarly journals Variations in the Initial Presentation of a Rare Congenital Adrenal Hyperplasia: Steroidogenic Acute Regulatory Deficiency

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A164-A164
Author(s):  
Priyanka Saha ◽  
Juanita Hodax ◽  
Sara A DiVall ◽  
Grace Kim ◽  
Alyssa Huang
Keyword(s):  
Genetic Analysis ◽  
Congenital Adrenal Hyperplasia ◽  
Sex Reversal ◽  
Full Term ◽  
Adrenal Crisis ◽  
Acth Level ◽  
Adrenal Hyperplasia ◽  
Pelvic Mri ◽  
Steroidogenic Acute Regulatory ◽  
Star Gene

Abstract Background: Steroidogenic Acute Regulatory (StAR) deficiency is a rare form of congenital adrenal hyperplasia characterized by dysregulated cholesterol transport mediated by StAR enzyme across mitochondrial membranes. Adrenal dysfunction is due to the two-hit hypothesis: 1) defective StAR protein and 2) cholesterol accumulation in the adrenals and gonads. With variable cellular damage, adrenal crisis can occur early or late. Clinical cases: We present two cases of StAR deficiency with contrasting presentations. Case 1: A 9-day old ex full term female from a nonconsanguineous union presented to a rural hospital with hypothermia, lethargy, and poor feeding. She had hypoglycemia 41 mg/dL (60–105), hyponatremia 120 mEq/L (135–145), hyperkalemia 7.7 mEq/L (3.5–5.5) and cortisol < 0.4 ug/dL (4.5–23). Baby was started on hydrocortisone (HCT) 100 mg/m2 and one-time fludrocortisone (FCT). She decompensated requiring chest compressions, intubation and pressors. She was transferred to our institution. Newborn screen was normal; she had typical female external genitalia. US demonstrated a uterus; ovaries and adrenals were not identified. Upon extubation and clinical improvement, her HCT was weaned to physiologic doses. She became hyponatremic requiring FCT and salt supplements. Post-HCT wean, ACTH level was 304 pg/mL (7–63) with aldosterone < 4.0 ng/dL (6.5–86). Karyotype was 46,XX. Genetic analysis revealed a novel heterozygous likely pathogenic variant in the STAR gene, (STAR c.65-12_68del variant) without defect in the other STAR gene. Case 2: A 9-month-old ex full-term female of Iraqi descent from a nonconsanguineous union presented with fatigue, poor oral intake and weight loss from 50%-ile to 3%-ile. She had hyponatremia 122 mEq/L, hyperkalemia 8.0 mEq/L, but was normoglycemic. She was normotensive; EKG was normal. Parents noted progressive hyperpigmentation including her gums, palmar and plantar creases. She had typical external female genitalia with a hypoplastic clitoris (2 mm x 2 mm). ACTH stimulation test showed low cortisol (0.5 ug/dL) at 60 minutes. She was treated with HCT 100 mg/m2 for 5 days, then tapered to maintenance dosing, with FCT and salt supplements. Her ACTH level returned > 5000 pg/ml. Aldosterone, 17-OH-Progesterone, 17-OH-Pregnenolone, 11-Deoxycortisol and androstenedione were undetectable. Pelvic US did not identify uterus or ovaries. Pelvic MRI identified bilateral inguinal testes with enlarged adrenal glands. Karyotype was 46, XY. We suspected StAR deficiency with sex-reversal. Genetic analysis revealed a known homozygous mutation in STAR (c.545G>A). Conclusion: StAR deficiency is clinically indistinguishable from P450scc deficiency and genetic testing is needed. Both entities can present with early or delayed adrenal crisis. While classic for StAR deficiency, adrenal enlargement is inconsistent. Karyotype is vital to identify sex reversal.

scholarly journals Identification of Novel Mutations in STAR Gene in Patients with Lipoid Congenital Adrenal Hyperplasia: A First Report from India

2013 ◽  
Vol 5 (2) ◽  
pp. 121-124 ◽  
Author(s):  
Vasudevan Lakshmi ◽  
Joshi Rajesh ◽  
Kumar Das Dhanjit ◽  
Rao Sudha ◽  
Sanghavi Daksha ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adrenal Hyperplasia ◽  
Novel Mutations ◽  
First Report ◽  
Star Gene

scholarly journals Cardiac Arrest in a Child with Non-classic Lipoid Congenital Adrenal Hyperplasia Associated with a New STAR Gene Mutation

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A122-A122
Author(s):  
Yun Yan ◽  
Isabelle Thiffault ◽  
Sarah Tsai ◽  
Luke He ◽  
Francesco De Luca
Keyword(s):  
Cardiac Arrest ◽  
Genetic Testing ◽  
Congenital Adrenal Hyperplasia ◽  
Adrenal Insufficiency ◽  
Clinical Features ◽  
Urgent Care ◽  
High Dose ◽  
Adrenal Hyperplasia ◽  
Care Clinic ◽  
Star Gene

Abstract Introduction: Steroidogenic acute regulatory (STAR) protein regulates steroid hormone synthesis by transporting cholesterol into mitochondria. STAR gene mutations lead to lipoid congenital adrenal hyperplasia (LCAH), the rare but most severe form of congenital adrenal hyperplasia in children. We present an unusual case with an episode of cardiac arrest in a young girl during an acute febrile illness and later she was diagnosed with adrenal insufficiency secondary to a non-classic LCAH. Case: 2-year 11-month-old previously healthy white female was brought to an urgent care clinic due to severe lethargy and a seizure-like activity during a fever illness. She was found to have an undetectable blood glucose level and went into cardiac arrest shortly after arrival. CPR was performed for approximately 11 minutes. She then developed sever respiratory distress and was intubated. She was transferred to the PICU with IV sodium bicarbonate given en route. On admission, her body weight was 13.26 kg (36.80th percentile), height 90 cm (17.56th percentile), and BMI 16.17 (62.88th percentile). Her physical exam revealed normal external female genitalia and normal skin pigmentation. Lab evaluation revealed normal sodium and potassium but elevated anion gap, hyperuricemia, elevated creatinine kinase, abnormal liver function tests and abnormal coagulation profile. Brain MRI revealed findings consistent with hypoxic-ischemic encephalopathy. Renal function improved within 24 hours and hepatic function returned to normal after 20 days. Due to her severe hypoglycemic event, a high-dose ACTH stimulation test was performed. The results were consistent with adrenal insufficiency: baseline cortisol level, 7.3 μg/dL; 30 minutes cortisol, 7.8 μg/dL; 60 minutes cortisol, 9 μg/dL (normal response, ≥18 mcg/mL at 30 or 60 minutes). The baseline ACTH level was significantly elevated, 1688 pg/mL (0–46) as well as the renin activity, 24.3 ng/hour (1.7–11.2). Genetic testing revealed a 46 XX karyotype. STAR gene analysis identified compound heterozygosity; a novel deletion (c.811delC, p.Leu271Cysfs*50) and a previously reported missense mutation (c.661G>A, p.Gly221Ser). The girl is now 11 years old and exhibits normal growth, normal cognitive development, and she has developed early signs of puberty (Tanner stage 2 for breast). She takes daily hydrocortisone, fludrocortisone and stress dose hydrocortisone as needed. Conclusion: In non-classic LACH, the onset is generally late or not acute. Initial clinical features are variable and nonspecific. For this reason, non-classic LCAH may be overlooked. Adrenal crisis is a life-threatening complication, and it is important that clinicians are aware of the clinical features of non-classic LCAH and consider it in the differential diagnoses. Genetic testing for STAR should be considered in individuals with non-autoimmune primary adrenocortical insufficiency.

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