CYP21 genotype, adult height, and pubertal development in 55 patients treated for 21-hydroxylase deficiency.
In a retrospective study we evaluated long-term growth, pubertal developmental patterns to final height (FH), and medication in 55 patients (35 females) affected by 21-hydroxylase deficiency. The patients were classified into 3 groups according to predicted mutation severity: group A (11 women and 9 men), homozygous or compound heterozygous for null or In2 splice mutations [residual enzymatic activity (RA), <1%]; group B (11 women and 4 men), homozygous for I172N or R341P or R426H mutations (RA, approximately 2-3%) or compound heterozygous with any of the group A or B mutations; and group C (13 women and 7 men), homozygous for P30L or V281L or P453S mutations (RA, >30%) or compound heterozygous with any of the group A, B, or C mutations. Three patients showed unclassifiable genotypes. FH was similar in the female groups, whereas male patients in group B were shorter than males in groups A and C. Fifty-five percent of patients in group A, 33% in group B, and 40% in group C reached an FH within 0.5 SD of target height. Four of the 7 patients diagnosed via neonatal screening achieved an FH equal to or above the target height. In the entire group, early diagnosis (<1 yr) improved height outcome. Early diagnosed CAH patients who received lower cortisol equivalent doses during the first year of life reached a better FH. Our results underline the importance of mineralocorticoid therapy, as CAH subjects in groups A and B who did not receive this treatment showed reduced FH. Early diagnosis, the use of more physiological cortisol equivalent dosages during the first year of life, and the extension of mineralocorticoid therapy to all classical patients are shown to improve the auxological outcome. Genotypic analysis helped to interpret the height results of our cases and prospectively may represent a useful tool for improving the therapeutic choice and the height outcome.
Balsamo
Antonio
A
Department of Pediatrics, University of Bologna and S Orsola-Malpighi Hospital, 40138 Bologna, Italy. antonio.balsano@unibo.it
Cicognani
Alessandro
A
Baldazzi
Lilia
L
Barbaro
Michela
M
Baronio
Federico
F
Gennari
Monia
M
Bal
Milva
M
Cassio
Alessandra
A
Kontaxaki
Krissi
K
Cacciari
Emanuele
E
D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D000375:Aging; D001827:Body Height; D002648:Child; D002675:Child, Preschool; D005260:Female; D005298:Fertility; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008901:Mineralocorticoids / Q000627:therapeutic use*; D011379:Prognosis; D011627:Puberty; D012189:Retrospective Studies; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
D008901:Mineralocorticoids; D013255:Steroid 21-Hydroxylase