ESPE Abstracts

Introduction: Adrenal insufficiency can be caused by different factors. Biotin deficiency is either nutritional or related to synthesis/recycling defects. We are reporting a rare case of adrenal insufficiency complicating a late diagnosis of holocarboxylase synthetase deficiency in an infant who also had protein-S-deficiency, later thought to be secondary.

Case: Term female infant born, to non-consanguineous parents, in good condition with birth-weight 3.1kg (10th-centile) developed extensive nappy dermatitis that was followed by erythematous scaly patches on her back and excoriation on her abdomen. She gained weight and crossed centiles by 2-month. At 3-month, the rash got worse, therefore she was prescribed mometasone1% cream and clotrimazole-betamethasone which the mother continued to apply in large amounts over large body areas for 2-months. At 5-months of age, she presented to the Emergency Department with an acute history of poor activity and respiratory distress. Examination revealed cushingoid appearance, weight 8.3 kg (>99th centile), with dry peeling, depigmented skin and necrosis of her right toe. She had volume and catecholamine refractory shock with severe lactic acidosis, hypoglycemia(1.4 mmol/l), hyperlactatemia(10 mmol/l), hypokalemia(2.7 mmol/l), hypernatremia(155 mmol/l), with cortisol(454nmol/l), normal renin(13.8mIU/L) and aldosterone(183pmol/l) levels. Adrenal insufficiency was considered and hydrocortisone (20mg/m²/day) was started. Lactic acidosis peaked to 19 mmol/l and started improving a week after hemodynamic stability to a baseline of 2-4 mmol/l. Thereafter, she developed hypertension despite halving the steroids. After 2-weeks of stability, she acutely developed irritability and acidotic breathing with similar biochemical derangements but with normal glucose and ammonia levels. However, she was more critical with increasing refractory lactic acidosis up to 21 mmol/l needing high inotropic support and hemodialysis to reduce acidosis. At that point, acylcarnitine profile in dried blood spots revealed significantly elevated 3-hydroxyisovaleryl-carnitine 9.23(0.05-0.29umol/L), with elevated free carnitine 496(10.3-56.9umol/L) that was secondary to carnitine supplementation. Significantly elevated 2-hydroxyisovaleric acid was also detected in urine organic acids. Biotin was initiated and the baby improved dramatically within 48-hours. The thrombophilia workup revealed functional protein-S 0.247(0.54-1.18u/ml). Whole exome sequencing revealed compound heterozygous mutations in HLCS gene, consistent with the diagnosis of holocarboxylase synthetase deficiency. No mutations were found to explain protein-S-deficiency.

Conclusion: Very rare presentation of three underlying pathologies, at one time. Hypernatremia, hypokalemia, obesity and hypertension were not reported previously in Biotin/holocarboxylase synthetase deficiency, two disorders notoriously known to be associated with failure to thrive. Steroid use should be restricted in infancy as it caused adrenal insufficiency in this case.