IMPE Abstracts

Congenital Lipoid Adrenal Hyperplasia (CLAH) is the most severe form of congenital adrenal hyperplasia. It is caused by mutation in the steroidogenic acute regulatory protein (StAR) gene, which can be of autosomal recessive inheritance. A 6-year-old girl, with a background of recurrent febrile seizure, presented with history of seizure, preceded by 1-day history of fever. On presentation, she had reduced consciousness, hypoglycemia with refractory hypotensive shock. She was intubated, critically ill, and treated as acute encephalopathy. In PICU, the patient received inotropes, antibiotics, anti-viral therapy, with plasma exchange and steroid pulses therapy. She was extubated after 5 days and the clinical condition gradually improved. MRI brain was suspicious of viral encephalitis. Infection screening revealed adenovirus infection. The patient had unremarkable birth history with normal developmental milestones. She is the second child in a non-consanguineous marriage. Her 11-year-old sister was diagnosed with CLAH since 3-year-old, presented with severe hyperpigmentation at her fingers and nail bed, and history of recurrent seizures. The genetic study of her sister confirmed StAR gene mutations, similar to her parents who were both asymptomatic. On examination, her height was 123.9 cm at +2.44 SD, and weight was 22.1 kg at +1 SD. She was not dysmorphic. There was hyperpigmentation on her fingers, nailbeds, lips and gingiva. Biochemical investigations revealed abnormalities in the glucocorticoid and mineralcorticoid parameters. Her cortisol while in PICU was only 0.23 µg/dL (7.07 – 19.6 µg/dL) despite being ill, with repeat cortisol also low at 2.17 µg/dL. ACTH was markedly elevated at 1560 pg/mL (7.2 – 63.3 pg/ml). The electrolytes were within normal range; sodium at 135 -139 mEq/L, and potassium at 3.7 – 4.3 mEq/L, however, renin was elevated at 9.0 ng/mL/H (0.2 – 2.3 ng/mL/H) and aldosterone was at lower side of normal, 10 pg/mL (4 – 82.1 pg/mL). Karyotype was 46,XX. ACTH stimulation test showed poor baseline and suppressed peak cortisol at 1.78 and 1.64 µg/dL respectively. Genetic mutation analysis revealed 2 mutations in the StAR genes which are similar to her elder sister; heterozygous mutation in exon 7, c.814C>T (p.Arg272Cys) inherited from the father, and heterozygous mutation in exon 1, c.64+1delG, inherited from the mother. The patient is currently well. She is on hydrocortisone 12 mg/day (13 mg/m2/day). This case illustrates that even though similar StAR gene mutations are present within a family, the onset of clinical manifestations may differ.