الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Congenital adrenal hyperplasia (CAH) is one of the most common inborn endocrine disorders. It comprises a group of autosomal recessive disorders resulting from the deficiency of one of the five steroidogenic enzymes required for cortisol biosynthesis in the adrenal cortex. Steroid 21 hydroxylase deficiency is the most common form of CAH, accounting for 90-95% of all cases.
Steroid 21-hydroxylase normally catalyzes some reactions in cortisol and aldosterone biosynthesis. Deficiency of this enzyme leads to impaired adrenal steroid hormone synthesis. The result is an increased secretion of the adrenal corticotropic hormone from the pituitary gland with subsequent adrenal hyperplasia and overproduction of androgen.
The clinical phenotype is classified as classic, the severe form, and nonclassic (NC), the mild form. Classic CAH occurs in 1:15,000 live births and is subclassified as salt-wasting (SW) and simple virilizing (SV), reflecting the degree of aldosterone deficiency. The incidence of NC CAH is estimated to be approximately 1:1000.
Classic 21-hydroxylase deficiency is the most common cause of ambiguous genitalia in females. The salt-wasting form is characterized by prenatal virilization in females and life-threatening salt-wasting crisis in the neonatal period in both sexes. Classic simple virilizing form is characterized by prenatal virilization in females and pseudoprecocious puberty in males and females. The non classic form may be asymptomatic or associated with premature pubarche in children and acne, hirsutism, and menstrual irregularities in women.
The gene encoding steroid 21-hydroxylase (CYP21A2), and a nonfunctional, closely linked pseudogene, (CYP21A1P) are located on chromosome 6p21.3. Both genes consist of 10 exons sharing a high degree of homology with a nucleotide identity of 98% on exon and of 96% on intron level. The high homology of these duplicated regions causes misalignment during meiosis, resulting in genetic defects. This accounts to approximately 95% of all mutated CYP21A2 alleles. The remaining 5% of the mutations are population specific and are not derived from the pseudogene.
Laboratory studies to diagnose 21- hydroxylase deficiency in an infant with ambiguous genitalia include karyotype, serum 17-hydroxyprogesterone (17-OHP) determination, abdominal/pelvic ultrasound to identify the uterus, and molecular genetic testing.
The medical treatment in 21-OHD aims to replace the deficient glucocorticoids and mineralocorticoids, thereby suppressing ACTH concentrations and normalizing adrenal androgens, without impairing growth while allowing for normal pubertal development and fertility.
The aim of the present study was to detect the selected four common CYP21A2 gene mutations, (8-bp deletion, IVS2–13A/C-G, I172N, and V281L) to confirm the diagnosis of patients with congenital adrenal hyperplasia due to 21- hydroxylase deficiency, allowing proper management and genetic counseling.
This study was conducted on 20 patients with CAH due to 21 OHD. All patients were subjected to careful history taking, complete clinical examination, pelvic sonography, biochemical assays, cytogenetic examination, molecular studies for detection of the four common CYP21 gene mutations (8-bp deletion, IVS2–13A/C-G, I172N, and V281L). Lastly, patients and their families were offered proper genetic counseling.
The results of this study revealed the following:
• Parental consanguinity among the studied patients was 85% with high first cousin marriages (59%).
• Among 20 patients with CAH, 5 patients were phenotypically males and 15 were of ambiguous sex. The cytogenetic analysis revealed that 3 phenotypically males (15%) showed male karyotype (46,XY), and the other 17 patients (85%) had female karyotype (46,XX).
• All patients had a classical form of 21-hydroxylase deficiency. Fourteen patients (70%) presented with the SW form, and 6 patients (30%) with the SV form.
• The screened 4 mutations were identified in 25% (5/20) of the studied patients.
• Each of 8 bp deletion in exon 3 and (IVS2–13A/C-G) mutation was detected in 2 patients (10%) with SW form. Only 1 patient (5%) with SV form was carried the I172N mutation. All patients with detected mutations had homozygous genotype. While, V281L mutation in exon 7 could not be found in our studied group.