Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical pseudo-hurler polydystrophy) are caused by mutations in the GlcNAc-phosphotransferase alpha beta -subunits precursor gene.
The aim of the present study was to search for defects in the CYP21 gene in children with PA and to detect possible correlations of the molecular defect to pertinent hormonal and clinical data.
To determine the role of 21-hydroxylase (CYP21) gene mutations in these disorders, we performed molecular genotype analysis on 48 children and adolescents referred for evaluation of hyperandrogenic findings and diagnosed as having premature adrenarche or functional androgen excess.
The PA girls with menarche had lower birth length (BL) and higher prepubertal insulin-like growth factor 1 (IGF-1) concentrations compared with non-menarcheal PA girls.
AMH was significantly higher in girls with premature adrenarche (2.95 ± 1.20 ng/mL) compared with normal prepubertal girls (2.00 ± 0.95 ng/mL; P < .001), whereas their body mass index SD score was similar (P > .05).
Premature adrenarche (PA) was the most common pre-pubertal diagnosis (61%), characterized by DHEAS excess in 85%, while A4 and testosterone were only increased in 26 and 9% respectively.
DHEAS, testosterone, and androstenedione were increased in premature adrenarche, whereas sex hormone binding globulin was decreased in girls with premature adrenarche.
We hypothesized that genetic variation in low density lipoprotein (LDL) receptor-related protein 5 (LRP5), which is involved in Wnt signalling in the adrenal cortex and in cholesterol metabolism, plays a role in the pathogenesis of PA.
In conclusion, the minor variant at FTO rs9939609 seems to play no major role in the increased weight-for-height of PA subjects; but the risk allele at TCF7L2rs7903146 may have a role in the pathogenesis of PA in lean subjects.
In children with PA, the polymorphism associated with higher baseline serum dehydroepiandrosterone (p = 0.03), androstenedione (p = 0.02), plasma ACTH (p = 0.03) levels and with lower birth weight (p = 0.02).
The frequency of the MC2R -2 T>C polymorphism was significantly higher in PA children with premature pubarche than in those with milder signs of PA or in control children (p = 0.04).