Abstract |
In neonates with 21-hydroxylase deficiency the specific marker 11-oxo-pregnanetriol is at low levels in the first days of life and this drives the search for alternatives. We describe the structural characterisation of a new early marker, 3beta,16alpha,17alpha-trihydroxy-5alpha-pregnane-7,20-dione. Urine samples from 87 untreated and 11 recently treated newborns with 21-hydroxylase deficiency (42 males and 56 females) between birth and 40 days of age and control samples from 7 healthy neonates (4 males, 3 females) were compared. Steroids were analyzed as methyloxime-trimethylsilyl ether derivatives by GC-MS and GC-MS/MS, after extraction and enzymatic conjugate hydrolysis. Microchemical methods and deuterated derivatives were used. The new steroid was identified by comparison with 3beta,16alpha,17alpha-trihydroxy-preg-5-en-20-one and 3beta-hydroxy-5alpha-pregnane-7,20-dione standards. It was present for the first 4 weeks after birth (with a maximum around day 4) and showed a marked inter-individual variability. No effect of treatment was evident and levels were much higher than for 11-oxo-pregnanetriol in the first days of life. Only traces were found in controls. The likely involvement of oxysterol 7alpha-hydroxylase (CYP7B1) from the 'acidic' pathway of bile acid synthesis and 11beta-hydroxysteroid dehydrogenase-1 in the generation of the 7-oxo group is discussed. We conclude that this steroid is a useful early marker of 21-hydroxylase deficiency.
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Authors | Sofia Christakoudi, David A Cowan, Norman F Taylor |
Journal | The Journal of steroid biochemistry and molecular biology
(J Steroid Biochem Mol Biol)
Vol. 121
Issue 3-5
Pg. 574-81
(Aug 2010)
ISSN: 1879-1220 [Electronic] England |
PMID | 20302934
(Publication Type: Journal Article)
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Copyright | Copyright 2010 Elsevier Ltd. All rights reserved. |
Chemical References |
- 3beta,16alpha,17alpha-trihydroxy-5alpha-pregnane-7,20-dione
- Biomarkers
- Pregnanediones
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Topics |
- Adrenal Hyperplasia, Congenital
(diagnosis)
- Biomarkers
(urine)
- Case-Control Studies
- Early Diagnosis
- Gas Chromatography-Mass Spectrometry
- Humans
- Infant, Newborn
- Pregnanediones
(urine)
- Tandem Mass Spectrometry
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