3. DISORDER GENE AFFECTED
AND
CHOROMOSOME
SIGN AND SYMP. THERAPEUTIC
MEASURES
21 Hydroxylase
Deficiency ,classic
form
CYP21
6p21.3
Glucocorticoids deficiency
Mineralocorticoid deficiency
(salt –wasting crisis)
Ambiguous genitalia in
females
Postnatal virilization in males
and females
Glucocorticoids
replacement
Mineralocorticoids
+sodium chloride
supplements
Vaginoplasty and
clitoral recession
Suppression with
glucocorticoids
21-Hydroxylase
deficiency ,non
classic form
CYP21
6p21.3
Asymptomatic ,precocious
adrenarche
,hirsutism,acne,menstrual
irregularity ,infertility
Suppression with
glucocorticoids
11beta-
hydroxylase
deficiency
CYP11B1
8q24.3
Glucocorticoids deficiency
Ambiguous genitalia in
females
Postnatal virilization in males
and females
Hypertension
Glucocorticoids
replacement
Vaginoplasty and
clitoral recession
Suppression with
glucocorticoids
Suppression with
4. DISORDER AFFECTED
GENE AND
CHROMOSOME
SIGN AND SYMPTOMS THERAPEUTIC MEASURES
3beta-
hydroxysteroid
dehydrogenase
deficiency
,classic form
HSD3B2
1p13.1
Glucocorticoids deficiency
Mineralocorticoid deficiency
(salt –wasting crisis)
Ambiguous genitalia in females
and males
Precocious adrenarche
,disordered puberty
Glucocorticoids
replacement
Mineralocorticoids
+sodium chloride
supplements
Surgical correction +
sex hormone
replacement
Suppression with
glucocorticoids
17alpha-
hydroxylase/17,
20-lyase
deficiency
CYP17
10q24.3
Cortisol deficiency
Ambiguous genitalia in males
Sexual infantilism
Glucocorticoids
administration
Orchidopexy or
removal of
intraabdominal testes
,sex hormone
replacment
Sex homone
replacement
Suppression with
5. DISORDER AFFECTED GENE
AND CHROSOME
SIGN AND SYMPTOMS THERAPEUTIC
MEASURES
Congenital
lipoid
adrenal
hyperplasi
a
STAR
8p11.2
Glucocorticoids deficiency
Mineralocorticoid deficiency
(salt –wasting crisis)
Ambiguous genitalia in males
Poor pubertal development
or premature ovarian failure
in females
Glucocorticoids
replacement
Mineralocorticoids
+sodium chloride
supplements
Orchidopexy or
removal of
intraabdominal
testes,sex hormone
replacement
Estrogen replacement
P450
oxidoredu
ctase
deficiency
POR
7q11.3
Glucocorticoids deficiency
Ambiguous genitalia in males
and females
Maternal virilization
ANTLEY BIXLER SYNDROME
Glucocorticoids
replacement
Surgical correction of
genitals and sex
hormone
replacement
6. CLASSIC 21- HYDROXYLASE DEFICIENCY
GLUCOCORTICOIDS
( For children) Dose = Hydrocortisone 10 – 20 mg/m
sq./day in three divided dose .
For adults Prednisolone 5-7.5 mg daily in two divided dose .
7. Look for signs of Iatrogenic Cushing’s Syndrome
rapid weight gain
Hypertension
pigmented striae
osteopenia .
Male with testicular adrenal rests requires higher doses of
dexamethasone to suppress corticotrophin .
Treatment is not indicated in asymptomatic children non
classic 21-hydroxylase deficiency .
8. MINERALOCORTICOIDS
Supplemental mineralocorticoid
(0.1 – 0.2 mg of fludrocortisone daily )
sodium chloride
(17 – 34 mmol od sodium chloride daily in addition to
glucocorticoids treatment ).
Breast milk or infant formulas ( sodium contents 8mmol
per litre ) is insufficient to compensate sodium losses .
9. Monitor Plasma renin activity levels or direct renin
immunoassays .
Signs of inadequate dose
Hypotension
Hyperkalemia
elevated renin levels
Signs of overdose
Hypertension
Edema
Tachycardia
suppresses plasma renin activity .
Adjustment dose is 0.05 – 0.1 mg .
11. Prenatal genetic counselling is advised for all affected
females .
Maternally administered dexamethasone reduces genital
ambiguity in affected females foetuses .
Dose =20ug per kg /day .
Long term safety of prenatal treatment remains uncertain.
No congenital malformations have been attributable to
such therapy
12. ALGORITHM FOR DECISIONS PERTAINING TO THE
PRENATAL DIADNOSIS AND TREATMENT OF 21
HYDROXYLASE DEFEICIENCY ....
13. Both parents carrier
Pregnancy test (<6 week of gestation )
Positive
Begin dexamethasone Chronic villus sampling
Fetal sex Male-stop Dexa.
Female long term follow up
