Introduction: Congenital lipoid adrenal hyperplasia (CLAH) is rare and caused by mutations in the steroidogenic acute regulatory (STAR) gene, which is involved in a key step in the synthesis of pregnenolone from cholesterol. Cases typically present in the first days of life with severe adrenal crisis, salt wasting and severely disrupted androgen secretion which may result in sex reversal in 46, XY individuals.
Case report: We present a 21-month-old female and her younger brother. She first presented to her local hospital with tonsillitis, initial blood sugar was 1.6 mmol/l, serum sodium 126 mmol/l and a random cortisol of 69 nmol/l (full biochemistry at presentation is described in table below). She was born at term and was otherwise well apart from two previous admissions with tonsillitis and hypoglycaemia. The younger sibling presented at 22 months of age with increased skin pigmentation. Genetic testing revealed no mutations in NR0B1 (DAX1), MC2R or MRAP genes, initial genetics for other causes of isolated adrenal insufficiency were negative. Later re-testing showed the siblings to have compound heterozygous STAR mutations p.G221S and p.G201D, the former previously reported and the latter a novel mutation.
|Sibling 1||Sibling 2||Normal values|
|Age at presentation||22 months||21 months|
|Karyotype/Phenotype||XX - female||XY - male|
|Na+ at presentation||126||135|
|K+ at presentation||4.2||5.8|
|Synacthen test (cortisol in nmol/l)||56-57-55||295-323-311||Peak >550 nmol/l|
|17-OHP||<1 nmol/l||<1 nmol/l|
|Very long chain fatty acids||Normal||Normal|
|Urine Steroid Profile||Normal||Normal|
Conclusions: A diagnosis of CLAH should be considered even in children presenting with primary adrenal insufficiency (PAI) presenting outside the neonatal period. When the aetiology of PAI is uncertain in an index case, prompt investigation of siblings for evidence of evolving PAI should be considered. Our cases highlight a novel STAR mutation, p.G201D, and the advantage of newer sequencing methods that permit concomitant sequencing of more than one gene.
22 - 24 Nov 2017
British Society for Paediatric Endocrinology and Diabetes