Abnormal Glycerol Metabolism in a Child with Global Developmental Delay, Adrenal Insufficiency, and Intellectual Disability

After an uncomplicated birth and initial symptom-free period, a 7-day-old male infant presented with poor feeding, hypotension, hyponatremia (123 mmol/L; reference interval, 135–148), hyperkalemia (9.0 mmol/L; reference interval, 3.5–5.5), and increased blood urea nitrogen. A diagnosis of primary adrenal insufficiency was made following an adrenal ultrasound remarkable for no discernable adrenal tissue. Subsequent fluorescent in situ hybridization studies revealed deletions in the region containing the NR0B1 ,5 IL1RAPL1 , and GK genes in both the patient (for which he was treated with adrenocorticosteroids) and his asymptomatic mother. At approximately 4 years of age, he experienced a hypoglycemic episode (plasma glucose, 42 mg/dL). Fasting triglyceride level was also increased at 465 mg/dL (reference interval, <250). Approximately 1 year later, he presented again to the emergency room with vomiting, headaches, lethargy, cramps, and diarrhea. Clinical examination showed a developmentally delayed child with hypotonia and strabismus. He had iatrogenic Cushing syndrome. There was evidence of microorchidism, meatal stenosis, congenital hydroceles, and bilateral inguinal hernia. As part of follow-up studies, an array comparative genomic hybridization was performed. A urine specimen was also collected for organic acid analysis using GC-MS (Fig. 1). Fig. 1. Organic acid analysis of patient urine using GC-MS. Urine organic acids were extracted into ethyl acetate/ether and converted to trimethylsilyl derivatives before analysis using a GC 6890N/MS 5975 system equipped …