Lipoid congenital adrenal hyperplasia

Lipoid congenital adrenal hyperplasia refers to an uncommon form of CAH resulting from defects in the earliest stages of adrenal cortisol synthesis: the transport of cholesterol into the mitochondria of the cells of the adrenal cortex and the conversion to pregnenolone. Lipoid CAH causes mineralocorticoid deficiency in all affected infants and children. XY infants (genetic males) are severely undervirilized and are usually assigned and raised as girls. The adrenals are large and filled with lipid globules derived from cholesterol. more...

What is CAH?

Congenital adrenal hyperplasia (CAH) refers to any of several autosomal recessive diseases resulting from defects in steps of the synthesis of cortisol from cholesterol by the adrenal glands. All of the forms of CAH involve excessive or defective production of sex steroids and can pervert or impair development of primary or secondary sex characteristics in affected infants, children, and adults. Many also involve excessive or defective production of mineralocorticoids, which can cause hypertension or salt wasting.

The most common type of CAH is due to deficiency of 21-hydroxylase and is covered in detail in the main article on congenital adrenal hyperplasia. Lipoid CAH is one of the less common types of CAH due to deficiencies of other proteins and enzymes involved in cortisol synthesis. Other uncommon types are described in individual articles (links below).

Lipoid congenital adrenal hyperplasia

Lipoid congenital adrenal hyperplasia results from defects in the steps from cholesterol to pregnenolone. The adrenals are large and filled with lipid globules derived from cholesterol. Life-threatening mineralocorticoid and glucocorticoid deficiency becomes apparent in infancy or early childhood. Sex steroid production is greatly impaired. XY infants (genetic males) are severely undervirilized so that the external genitalia at birth are female (normal or slightly virilized). XX infants have normal female anatomy and if their mineralocorticoid and glucocorticoid deficiencies are treated will often undergo spontaneous puberty. Lipid storage damages the adrenals and eventually the gonads as well, so that all persons with this condition have so far been infertile.

Pathophysiology and genetics of lipoid CAH

Our understanding of the molecular basis for this disease has been advanced in the last decade by better understanding of adrenal steroidogenesis as well as genetic studies of affected patients. It used to be assumed that lipoid adrenal hyperplasia resulted from a defect of the enzymes that converted cholesterol to pregnenolone. The conversion reactions are mediated by a single enzyme, formerly referred to as 20,22-desmolase, but now identified as P450scc (side chain cleavage enzyme). However, as of 2003, only a single case of lipoid adrenal hyperplasia due to a mutation and defect of P450scc has been identified.

All other cases of lipoid adrenal hyperplasia that have been studied have been found to be due to mutations of the gene for the enzyme which transports cholesterol into the mitochondria. This enzyme, steroidogenic acute regulatory protein, or StAR, is coded by a gene on 8p11.2. Inheritance is autosomal recessive. OMIM number is 20170 for the deficiency.

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