IGFALSgene is located in chromosome 16p13.3 encoding acid labile subunit which binds insulin-like growth factors (IGFs) to increase their half-life and vascular localization. The biallelic defect of this gene leads to acid-labile subunit deficiency characterized by postnatal growth retardation, insulin resistance, delayed puberty, and no growth hormone deficiency. A 5-year-old-boy was referred to as low IGF-1 and cortisol level. He presented with obesity and growth retardation. This subject was born in is 36 weeks and 6 days with 2.04 kg of birth weight. The height, weight, and body mass index were 104.7cm (-1.0 standard deviation score, SDS), 29.7kg (2.9 SDS), and 27.1 kg/m2 (3.2 SDS), respectively. He had acanthosis nigricans on neck, axillary, and inguinal area. He had severe obesity, obstructive severe sleep apnea, and heavy snoring and picking habitus were observed. Laboratory finding showed severely low levels of IGF-1 (4.55 ng/mL) and IGFBP3 (<500 ng/mL). Morning fasting glucose, insulin and glucose level was 3.9 ug/dL, 91.49 uIU/mL and 99 mg/dL. We performed methylation test for 15q11-12 Prader-Willi syndrome chromosome region and pituitary function test. All results were normal. His growth hormone peak provoked by hypoglycemia and L-dopa administration was normal (17.9 ng/mL and 7.36 ng/mL). The targeted exome sequencing for growth hormone resistance syndrome was done in this subject and the result revealed novel biallelic mutations, c.680C>A (p.Ala227Glu) and c.1897C>T (p.Arg633Trp), in IGFALSgene. Each mutation was inherited from his mother and father, respectively. We found an additional rare variant, c.1517G>A (p.Arg506Gln) in INSR gene. Here in, we report a Korean boy with novel compound mutations of IGFALSand likely pathogenic variant of INSR presenting with growth retardation, acanthosis nigricans, and severe obesity. The long-term effect of IGFs dysfunction on glucose metabolism, growth, puberty, and obesity in this subject should carefully be follow-up and we will assess the effectiveness of growth hormone.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology