Near-miss apparent SIDS from adrenal crisis.
OBJECTIVE
Adrenal crisis from salt-losing congenital adrenal hyperplasia (CAH) typically occurs in the first 2 weeks of life. We evaluated 3 infants with adrenal crisis who presented at 6 to 8 months of age with near-miss sudden infant death syndrome (SIDS).


METHODS
Three 46,XY phenotypic female infants presented near death at 6 to 8 months of age with adrenal crisis and unmeasurable steroid hormones consistent with congenital lipoid adrenal hyperplasia (lipoid CAH).


METHODS
We sequenced genes potentially causing this phenotype: steroidogenic acute regulatory protein (StAR), the cholesterol side-chain cleavage enzyme, adrenodoxin reductase, adrenodoxin, and steroidogenic factor 1 (SF1). Site-directed mutagenesis and functional assays were performed for the missense mutation.


RESULTS
Hormonal values showed complete absence of adrenal and gonadal steroids. Patient 1 was a compound heterozygote for missense mutation R140P and an mRNA splice donor site mutation in the StAR gene. The R140P mutation was wholly inactive in vitro. Patient 2 was homozygous for a 7 base pair StAR deletion causing a frameshift. No mutations were found in Patient 3, suggesting a novel disease.


CONCLUSIONS
Although genetic disorders of steroidogenesis typically present in the first month of life, some defects, especially those in StAR, can present in mid-infancy, when adrenal hyperplasias are rarely considered. Adrenal insufficiency is a subtle disorder that may cause cardiovascular collapse, causing unexplained infant death that resembles SIDS.
Gassner
Heidi L
HL
Department of Pediatrics, University of California, San Francisco, California 94143-0978, USA.
Toppari
Jorma
J
Quinteiro González
Sofa
S
Miller
Walter L
WL
D000312:Adrenal Hyperplasia, Congenital / Q000150:complications* / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007223:Infant; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics; D013398:Sudden Infant Death / Q000209:etiology* / Q000235:genetics; D000098682:Steroidogenic Acute Regulatory Protein
D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein