Two siblings with lipoid congenital adrenal hyperplasia: first reported case in Serbia and literature review

Background Lipoid congenital adrenal hyperplasia (LCAH) is an uncommon but life-threatening autosomal recessive disorder. It is caused by a mutation in the steroidogenic acute regulatory protein (StAR), encoded by the STAR gene. Methods Clinical manifestations of two siblings with primary adrenal insufficiency (PAI) were described. A female infant was admitted to the hospital at six months of age for vomiting and failure to thrive. The diagnosis of PAI of unknown etiology was established. The girl’s younger brother was diagnosed with PAI at the age of 1.5 years during a febrile illness. His external genitalia showed undescended testes, scrotal hypoplasia, and hypospadia. Their family history was normal, and both parents were healthy. Clinical exome sequencing was used to identify mutations in candidate genes. Results Two heterozygous STAR mutations, p.Trp250Ter and p.Arg188Cys, were identified in both children. The mother was heterozygous for the p.Trp250Ter mutation, and the father was heterozygous for the p.Arg188Cys mutation. Conclusion Glucocorticoid, mineralocorticoid, and sex hormone therapy should be individualized according to the clinical presentation and laboratory findings. Because genotype and phenotype do not correlate consistently in LCAH, therapy and follow-up must be individualized.