First Korean case of NANS gene mediated deficiency of N-acetylneuraminic acid synthase causing late onset progressive skeletal dysplasia.

Backgrounds: Deficiency of N-acetylneuraminic acid synthase (NANS) impair the endogenous synthesis of sialic acid and accumulation of its precursor, which can cause infantile onset multisystemic disorders with skeletal dysplasia. Here we report the first Korean case of NANS deficiency patient presenting late onset skeletal dysplasia.

Case study: 10-year-old boy was referred to a pediatric endocrinology clinic with incidental x-ray findings suspected of metabolic bone disease. He was born at a gestational age of 39 weeks with a height of 49 cm, a weight of 2870 grams, and a head circumference of 30 cm from non-consanguineous parents. Postnatal magnetic resonance brain was performed in the neonatal period for evaluating fetal-onset ventriculomegaly and periventricular cyst, and its result showed persistent cavum septum pellucidum, bilateral connate cysts abutting the frontal horn of lateral ventricle, shallow frontal sulci. He had global developmental delay and intractable seizures. Besides, he also had comorbidity of chronic idiopathic thrombocytopenia, laryngomalacia, neurogenic bladder, adrenal insufficiency, and hypothyroidism. X-ray findings showed bilateral lacy iliac crest, dysplastic acetabular fossa, abnormally shaped fragmented femur head, flat vertebral body, irregular endplate of the vertebral body, stippled calcification of ribs, which had not been identified on available x-ray at 3 years ago. Whole exome sequencing for differentiating skeletal dysplasia identified biallelic mutation of the NANS gene, c.[735G>A (p.Trp245Ter)];c.[68T>C (p.Ile223Thr)].

Conclusions: Although NANS deficiency is a multi-systemic involved congenital disorder of glycosylation, phenotypic variability presenting at different ages can delay accurate diagnosis. Whole exome sequencing should be considered in patients with skeletal dysplasia and neurodegenerative symptom.