Conference paper

Publication year: 2004

Pages: 957-964

Journal: Endocrine Research

Volume number: 30

Issue number: 4

ISSN: 0743-5800

DOI Link: https://doi.org/10.1081/ERC-200044174

Conference: 11th Conference on Adrenal Cortex

Publisher: Taylor and Francis Group

Abstract: 
We report on a male twin infant who presented with brachy-turri-cephaly, frontal bossing, large anterior fontanelle, low set and malformed ears, and mild arachnodactyly. He had normal male genitalia. There was no evidence for maternal virilization during pregnancy. The pattern of malformations resembled Antley-Bixler-Syndrome (ABS). However, sequencing analysis of the fibroblast growth factor receptor 2 gene (FGFR2) did not reveal mutations. The boy's twin sister did not show any somatic or endocrine abnormalities. In the boy, neonatal screening for congenital adrenal hyperplasia was positive with moderately elevated 17-hydroxyprogesterone. Sequence analysis of his CYP21 gene did not reveal any mutations. The short synacthen test revealed an exaggerated 17-hydroxyprogesterone and a blunted cortisol response. Urinary steroid profiling by gas chromatography-mass spectrometry (GC-MS) revealed a unique steroid metabolome suggestive of impaired activity of both 17-hydroxylase and 21-hydroxylase. Clinical and metabolic findings therefore were compatible with the recently described variant of congenital adrenal hyperplasia, P450 oxidoreductase deficiency (ORD). Subsequently, sequencing analysis of CPR, the gene encoding P450 oxidoreductase (OR), revealed a homozygous mutation in the patient, resulting in an amino acid exchange in position 284 of the OR protein (A284P). Both the female twin sister and the parents were heterozygous for the A284P mutation. P450 oxidoreductase deficiency represents a novel autosomal recessively inherited form of congenital adrenal hyperplasia. Its characteristic steroid metabolome can readily be detected by GC-MS analysis of spot urine. Clinical features may include an ABS phenotype, ambiguous genitalia (virilization in girls, feminization in boys), and glucocorticoid deficiency. If required, hydrocortisone replacement should be provided.

Harvard Citation style: Wudy, S., Hartmann, M., Draper, N., Stewart, P. and Arlt, W. (2004) A male twin infant with skull deformity and elevated neonatal 17-hydroxyprogesterone: A prismatic case of P450 oxidoreductase deficiency, Endocrine Research, 30(4), pp. 957-964. https://doi.org/10.1081/ERC-200044174

APA Citation style: Wudy, S., Hartmann, M., Draper, N., Stewart, P., & Arlt, W. (2004). A male twin infant with skull deformity and elevated neonatal 17-hydroxyprogesterone: A prismatic case of P450 oxidoreductase deficiency. Endocrine Research. 30(4), 957-964. https://doi.org/10.1081/ERC-200044174