Steroid Metabolism

cholesterol sources

• external (food, ect.)

• synthesized endogenously from other molecules

  • primarily in liver

smith lemli opitz syndrome (SLO)

• AR

• ID, autism, poor growth, microcephaly, 2-3 toe syndactyly, abnl brain imaging

• wide clinical spectrum

• low cholesterol thought to be driver of phenotype (important for cell signaling)

SLO treatments

• diet supplementation with extra cholesterol would help w some sx but not all (only so much extra cholesterol can do for structural brain abnormalities)

• bile acid supplementation to help with feeding difficulties

congenital adrenal hyperplasia (CAH)

• multiple forms of CAH that can be caused by different enzyme blockages

• 21 hydroxylase deficiency is most common

a _____ in the steroid synthesis pathway (by an enzyme) will cause lack of some steroids and a buildup of others

blockage

_______ and _______ are two major conditions associated w abnl cholesterol/steroid metabolism

CAH and SLO

salt wasting in untreated 21 hydroxylase deficiency

• poor feeding, failure to thrive, weight loss, dehydration, vomiting, low bp, metabolic acidosis

• leads to vascular collapse, shock, death

• can happen in first few weeks of life or throughout life

21 hydroxylase deficiency: virilization from increased androgens

• females born with ambiguous or externally male genitalia

• early excessive puberty in both sexes

• bases of children AFAB then being considered phenotypically male by toddler years

• fertility problems

21 hydroxylase deficiency: short stature

• advanced skeletal maturation from early puberty if under-treated

• over-treatment with steroid replacements

CAH treatments

• glucocorticoid replacement therapy (hydrocortisone)

• mineralcorticoid replacement therapy

  • for those w salt wasting CAH