Genomic coordinate (human 10:102,830,531 CYP17A1) & (mouse 19:46,655,604 Cyp17a1).
Cytoband ( human 10q24.32 CYP17A1) & (mouse 19qC3 Cyp17a1).
Here I present: “Congenital Adrenal Hyperplasia“, Victor McKusick, Mendelian Inheritance in Man’, 1966. 先天性腎上腺增生症。icd10=E25.0
INTRODUCTION.
Congenital adrenal hyperplasia (CAH) is a group of inherited disorders of adrenal steroid biosynthesis, present from birth, caused by enzyme deficiencies in the adrenal cortex.
1. Core biochemical idea.
CAH = blocked cortisol synthesis.
→ ↓ cortisol.
→ ↑ ACTH (loss of negative feedback).
→ adrenal hyperplasia.
→ steroid precursors diverted into androgen excess (most types).
2. Most common form (≈95%).
21-hydroxylase deficiency.
Gene: CYP21A2 (autosomal recessive)
Blocked steps.
Progesterone → deoxycorticosterone.
17-hydroxyprogesterone → 11-deoxycortisol.
Hormonal consequences.
↓ Cortisol.
± ↓ Aldosterone.
↑ Androgens.
3. Clinical phenotypes (21-hydroxylase).
A. Salt-wasting CAH (severe).
↓ Aldosterone → hyponatremia, hyperkalemia, dehydration.
Neonatal shock if untreated.
Ambiguous genitalia in XX infants.
B. Simple virilizing CAH.
Normal aldosterone.
Virilization without salt loss.
C. Non-classic CAH (mild)
Later onset (childhood/adulthood).
Hirsutism, acne, irregular menses, infertility.
4. Other CAH types.
Enzyme deficiency Key features.
11β-hydroxylase Hypertension (↑ DOC), virilization.
17α-hydroxylase Hypertension, hypokalemia, sexual infantilism.
3β-HSD Ambiguous genitalia in both sexes.
StAR (lipoid CAH).
Severe adrenal failure, undervirilized XY.
5. Diagnosis.
Newborn screening: ↑ 17-hydroxyprogesterone.
Electrolytes (salt-wasting).
ACTH stimulation test.
Genetic testing (CYP21A2).
6. Treatment principles.
Glucocorticoid replacement (hydrocortisone).
Mineralocorticoid (fludrocortisone) if salt-wasting.
Salt supplementation in infants.
Stress-dose steroids during illness.
Lifelong management.
7. Systems-level view. (engineering analogy).
CAH = control system failure.
Cortisol = feedback signal.
ACTH = controller output.
Enzyme defect = broken actuator.
Result: uncontrolled precursor flux into androgens.
CONCLUSION.
There is evidence that congenital adrenal hyperplasia can be caused by mutation in the cytochrome-P450 type-17A1 is an enzyme of the hydroxylase type that in humans is encoded by the CYP17A1 gene on genomic coordinate 10:102,830,531 and cytoband 10q24.32.
CYP17A1 is ubiquitously expressed in many tissues and cell types, including the zona reticularis and zona fasciculata of the adrenal cortex.
