First case report of rare congenital adrenal insufficiency caused by mutations in the CYP11A1 gene in the Czech Republic

2016 ◽  
Vol 29 (6) ◽  
Author(s):  
Renata Pomahačová ◽  
Josef Sýkora ◽  
Jana Zamboryová ◽  
Petra Paterová ◽  
Jana Varvařovská ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Adrenal Glands ◽  
External Genitalia ◽  
Side Chain ◽  
Primary Adrenal Insufficiency ◽  
The Czech Republic ◽  
Chain Cleavage ◽  
First Case ◽  
Cleavage Enzyme ◽  
Normal Laboratory

AbstractWe characterized a case of congenital adrenal insufficiency caused by cholesterol side-chain cleavage enzyme (P450scc) deficiency. The patient presented after birth with cardiopulmonary instability, hyponatremia, hyperkalemia, hypoglycemia and metabolic acidosis. We confirmed primary adrenal insufficiency. There were no signs of the external genitalia virilism. The replacement therapy with glucocorticoids and mineralocorticoids led to normal laboratory results. At the age of 12 years, we confirmed hypergonadotropic hypogonadism, which revealed disorder of steroidogenesis in the adrenal glands and in the gonads. The enzymatic block was found at the beginning of steroidogenesis. The mutation was confirmed in the

Heterozygous mutations in the cholesterol side-chain cleavage enzyme gene (CYP11A1) can cause transient adrenal insufficiency and life-threatening failure to thrive

HORMONES ◽  
2018 ◽  
Vol 17 (3) ◽  
pp. 419-421 ◽  
Author(s):  
Dimitrios T. Papadimitriou ◽  
Christina Bothou ◽  
Diagoras Zarganis ◽  
Maria Karantza ◽  
Anastasios Papadimitriou
Keyword(s):  
Adrenal Insufficiency ◽  
Failure To Thrive ◽  
Side Chain ◽  
Enzyme Gene ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Cleavage Enzyme ◽  
Life Threatening

scholarly journals Heterozygous Mutation in the Cholesterol Side Chain Cleavage Enzyme (P450scc) Gene in a Patient with 46,XY Sex Reversal and Adrenal Insufficiency

2001 ◽  
Vol 86 (8) ◽  
pp. 3820-3825 ◽  
Author(s):  
Toshihiro Tajima ◽  
Kenji Fujieda ◽  
Naoya Kouda ◽  
Jun Nakae ◽  
Walter L. Miller
Keyword(s):  
Adrenal Insufficiency ◽  
Cellular Damage ◽  
Dominant Negative Effect ◽  
Side Chain ◽  
Heterozygous Mutation ◽  
Adrenal Hyperplasia ◽  
Side Chain Cleavage ◽  
Congenital Lipoid Adrenal Hyperplasia ◽  
Chain Cleavage ◽  
Cleavage Enzyme

Cytochrome P450scc, the mitochondrial cholesterol side chain cleavage enzyme, is the only enzyme that catalyzes the conversion of cholesterol to pregnenolone and, thus, is required for the biosynthesis of all steroid hormones. Congenital lipoid adrenal hyperplasia is a severe disorder of steroidogenesis in which cholesterol accumulates within steroidogenic cells and the synthesis of all adrenal and gonadal steroids is impaired, hormonally suggesting a disorder in P450scc. However, congenital lipoid adrenal hyperplasia is caused by mutations in the steroidogenic acute regulatory protein StAR; it has been thought that P450scc mutations are incompatible with human term gestation, because P450scc is needed for placental biosynthesis of progesterone, which is required to maintain pregnancy. In studying patients with congenital lipoid adrenal hyperplasia, we identified an individual with normal StAR and SF-1 genes and a heterozygous mutation in P450scc. The mutation was found in multiple cell types, but neither parent carried the mutation, suggesting it arose de novo during meiosis, before fertilization. The patient was atypical for congenital lipoid adrenal hyperplasia, having survived for 4 yr without hormonal replacement before experiencing life-threatening adrenal insufficiency. The P450scc mutation, an in-frame insertion of Gly and Asp between Asp271 and Val272, was inserted into a catalytically active fusion protein of the P450scc system (H2N-P450scc-Adrenodoxin Reductase-Adrenodoxin-COOH), completely inactivating enzymatic activity. Cotransfection of wild-type and mutant vectors showed that the mutation did not exert a dominant negative effect. Because P450scc is normally a slow and inefficient enzyme, we propose that P450scc haploinsufficiency results in subnormal responses to ACTH, so that recurrent ACTH stimulation leads to a slow accumulation of adrenal cholesterol, eventually causing cellular damage. Thus, although homozygous absence of P450scc should be incompatible with term gestation, haploinsufficiency of P450scc causes a late-onset form of congenital lipoid adrenal hyperplasia that can be explained by the same two-hit model that has been validated for congenital lipoid adrenal hyperplasia caused by StAR deficiency.

scholarly journals Normal male external genitalia do not rule out CYP11A1 deficiency

2019 ◽  
Vol 12 (7) ◽  
pp. e228235
Author(s):  
Vijaya Sarathi ◽  
Chithambaram Nagalingam
Keyword(s):  
Adrenal Insufficiency ◽  
External Genitalia ◽  
Serum Cortisol ◽  
Normal Male ◽  
Sequencing Analysis ◽  
Primary Adrenal Insufficiency ◽  
First Case ◽  
Renin Level ◽  
Male External Genitalia ◽  
Female External Genitalia

Defects in the initial steps of steroidogenesis usually present with female external genitalia in both 46,XX and 46,XY. Hence, they are not often considered in the differential diagnosis of primary adrenal insufficiency children with normal male external genitalia. Here, we report a boy with normal male external genitalia who presented with hyperpigmentation since the age of 2 years but diagnosis was delayed till 11 years of age. Evaluation revealed low-serum cortisol with elevated adrenocorticotropic hormone and direct renin level confirming primary adrenal insufficiency. Clinical exome sequencing analysis revealed a homozygous c.1351C>T (p.R451W) mutation in exon 8 of the CYP11A1 gene which was confirmed on Sanger sequencing. Both parents were heterozygous for the variation. To conclude, we report the first case of CYP11A1 deficiency from India. The report reiterates the existence of non-classic CYP11A1 deficiency characterised by primary adrenal insufficiency and normal male external genitalia in 46,XY.

P450 side-chain cleavage enzyme autoantibodies in canine Addison's disease

2013 ◽  
pp. 1-1
Author(s):  
Alisdair Boag ◽  
Kerry McLaughlin ◽  
Mike Christie ◽  
Peter Graham ◽  
Harriet Syme ◽  
...  
Keyword(s):  
Addison’S Disease ◽  
Side Chain ◽  
Addison's Disease ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Cleavage Enzyme
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