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Long-term outcome of partial P450 side-chain cleavage enzyme deficiency in three brothers: the importance of early diagnosis.
- Source :
-
European journal of endocrinology [Eur J Endocrinol] 2020 Mar; Vol. 182 (3), pp. K15-K24. - Publication Year :
- 2020
-
Abstract
- Objective: CYP11A1 mutations cause P450 side-chain cleavage (scc) deficiency, a rare form of congenital adrenal hyperplasia with a wide clinical spectrum. We detail the phenotype and evolution in a male sibship identified by HaloPlex targeted capture array.<br />Family Study: The youngest of three brothers from a non-consanguineous Scottish family presented with hyperpigmentation at 3.7 years. Investigation showed grossly impaired glucocorticoid function with ACTH elevation, moderately impaired mineralocorticoid function, and normal external genitalia. The older brothers were found to be pigmented also, with glucocorticoid impairment but normal electrolytes. Linkage studies in 2002 showed that all three brothers had inherited the same critical regions of the maternal X chromosome suggesting an X-linked disorder, but analysis of NR0B1 (DAX-1, adrenal hypoplasia) and ABCD1 (adrenoleukodystrophy) were negative. In 2016, next-generation sequencing revealed compound heterozygosity for the rs6161 variant in CYP11A1 (c.940G>A, p.Glu314Lys), together with a severely disruptive frameshift mutation (c.790&#95;802del, K264Lfs*5). The brothers were stable on hydrocortisone and fludrocortisone replacement, testicular volumes (15-20 mL), and serum testosterone levels (24.7, 33.3, and 27.2 nmol/L) were normal, but FSH (41.2 µ/L) was elevated in the proband. The latter had undergone left orchidectomy for suspected malignancy at the age of 25 years and was attending a fertility clinic for oligospermia. Initial histology was reported as showing nodular Leydig cell hyperplasia. However, histological review using CD56 staining confirmed testicular adrenal rest cell tumour (TART).<br />Conclusion: This kinship with partial P450scc deficiency demonstrates the importance of precise diagnosis in primary adrenal insufficiency to ensure appropriate counselling and management, particularly of TART.
- Subjects :
- Adrenal Rest Tumor genetics
Adrenal Rest Tumor pathology
Adrenal Rest Tumor surgery
Adult
Child, Preschool
Disease Progression
Early Diagnosis
Family
Frameshift Mutation
Genetic Diseases, X-Linked genetics
Glucocorticoids metabolism
Hormone Replacement Therapy
Humans
Hyperpigmentation etiology
Hyperpigmentation genetics
Male
Pedigree
Phenotype
Testicular Neoplasms genetics
Testicular Neoplasms pathology
Testicular Neoplasms surgery
Treatment Outcome
Adrenal Hyperplasia, Congenital diagnosis
Adrenal Hyperplasia, Congenital genetics
Cholesterol Side-Chain Cleavage Enzyme deficiency
Cholesterol Side-Chain Cleavage Enzyme genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1479-683X
- Volume :
- 182
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- European journal of endocrinology
- Publication Type :
- Report
- Accession number :
- 31917682
- Full Text :
- https://doi.org/10.1530/EJE-19-0696