ESPE Abstracts

Introduction: Deficient anterior pituitary with variable immune deficiency (DAVID) syndrome is a rare condition characterized by symptomatic ACTH deficiency and primary hypogammaglobulinemia, caused by a heterozygous mutation in the NFKB2 gene (MIM#164012) on chromosome 10q24. We report the novel mutation of the NFKB2 gene in a Korean boy presenting with gait disturbance, calf pain, and abnormal thyroid function test.

Case: An 11-year-old Korean boy was presented with limb weakness and an abnormal thyroid function test. The laboratory finding showed an elevated level of creatinine kinase (CK) activity and subclinical hypothyroidism. He complained of leg weakness and calf pain during long walks. The targeted exome panel for neuromuscular disorder was performed, and a novel variant in the BAG3 gene, which is the causative gene for myopathy, myofibrillar 6 (MIM#612954), was identified. Segregation analysis showed that the subject’s mother carried this BAG3 variant, but she had no myopathic symptoms or signs. Since persistent subclinical hypothyroism was noted in this subject, thyroxine was started and a thyroid function test showed a euthyroid state. Additional whole exome sequencing (WES) was done to identify the causative gene for muscular symptoms and CK elevation. During the analysis of WES, he was admited to our hospital for acute sinusitis, and an immunologic evaluation was done for his low albumin and protein levels and sinusitis. Hypogammaglobulinemia including low immuloglobulin G (135 mg/dL) was identified. The novel truncating mutation in NFKB2 was found in this subject through WES. Segregation analysis for this NFKB2 mutation revealed de novo mutation. A pituitary function test and sella magnetic resoning imagin showed ACTH deficiency and an empty sella. The hydrocortisone (12 mg/m2/d) and immunoglobulin (30 mg/kg every 3weeks) was started. After medication, the patient’s symptoms, including muscle weakness, fatigue, and recurrent sinusitis were improving, and his growth velocity and pubertal progression were within the normal range until now.

Conclusion: In this study, we first report a case of DAVID syndrome caused by novel truncating NFKB2 mutation in a Korean boy presenting with calf pain and gait disturbance. Since DAVID syndrome is a treatable condition and the onset of adrenal insufficiency is between childhood and adolescence, it is important to differentiate this condition in children who present with atypical muscle symptoms, despite its rarity.