TY - JOUR
T1 - A new marker for early diagnosis of 21-hydroxylase deficiency: 3 beta,16 alpha,17 alpha-trihydroxy-5 alpha-pregnane-7,20-dione
AU - Christakoudi, Sofia
AU - Cowan, David A.
AU - Taylor, Norman F.
PY - 2010/8
Y1 - 2010/8
N2 - 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, 3 beta,16 alpha,17 alpha-trihydroxy-5 alpha-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 3 beta,16 alpha,17 alpha-trihydroxy-preg-5-en-20-one and 3 beta-hydroxy-5 alpha-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 7 alpha-hydroxylase (CYP7B1) from the 'acidic' pathway of bile acid synthesis and 11 beta-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. (C) 2010 Elsevier Ltd. All rights reserved.
AB - 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, 3 beta,16 alpha,17 alpha-trihydroxy-5 alpha-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 3 beta,16 alpha,17 alpha-trihydroxy-preg-5-en-20-one and 3 beta-hydroxy-5 alpha-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 7 alpha-hydroxylase (CYP7B1) from the 'acidic' pathway of bile acid synthesis and 11 beta-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. (C) 2010 Elsevier Ltd. All rights reserved.
U2 - 10.1016/j.jsbmb.2010.03.031
DO - 10.1016/j.jsbmb.2010.03.031
M3 - Article
VL - 121
SP - 574
EP - 581
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
IS - 3-5
ER -
