Clinical Utility of Congenital Disorder of Glycosylation Gene Panel in Patient with Refractory Epilepsy

ROA AC; MAXIT C; DENZLER I; ONNA N; KLEPPE S; ASTEGGIANO CG

Ciudad de Mexico

Congreso; 5th Latin American Congress of Glycobiology and 2nd. Meeting of the Glycoscience in Thematic Network; 2019

Sociedad Latinoamericana de Glicobiologia

CLINICAL UTILITY OF CONGENITAL DISORDER OF GLYCOSYLATION GENE PANEL IN PATIENT WITH REFRACTORY EPILEPSYRoa AC (1); Maxit C (2); Denzler I; Onna N (1); Papazoglu GM (3); Kleppe S (1); Asteggiano CG (3,4) (1) Sección Endocrinología, Metabolismo, Nutrición y Genética, Servicio de Clínica Pediátrica, Hospital Italiano de Buenos Aires. (2) Servicio de Neurología Pediátrica, Hospital Italiano de Buenos Aires. (3) Centro de Estudio de las Metabolopatias Congénitas (CEMECO - CONICET) Ferroviarios 1250, Hospital de Niños de la Sma. Trinidad, Córdoba, Argentina (UNC). (4) Cátedra de Farmacología, Facultad Medicina, Universidad Católica de Córdoba (UCC). Córdoba, Argentina.Introduction: Congenital Disorders of Glycosylation (CDG) are a growing group of multisystemic diseases caused by defects in the formation or processing of glycoproteins and/or glycolipids. Most types of CDGs present in early infancy and the clinical manifestations may include failure to thrive, hepatopathy, hypoglycemia, protein-losing enteropathy, developmental delay, hipotonia, neurologic abnormalities, eye abnormalities, immunologic, skin and skeletal findings. Type I CDG includes a group of disorders where there are defects in the biosynthesis of dolichol-linked oligosaccharides in the cytosol or endoplasmic reticulum (ER), as well as defects involving the transfer of oligosaccharides onto nascent glycoproteins. CDG-IK is a type I CDG caused by homozygous or compound heterozygous mutation in ALG1 gene (OMIM605907), encoding beta-1,4-mannosyltransferase on chromosome 16p13. This type of CDG is characterized by predominant neurologic involvement.Case Report: We present a patient referred at one year for refractory seizures, lack of eye contact, failure to thrive, developmental delay and acquired microcephaly. She had mild hyperammonemia, abnormal coagulation studies, her LFTs were elevated and cholesterol was low. Her brain MRI showed cortical and central atrophy, visual evoked potentials showed axonal neuropathy and electroretinography has a normal response. Methodology and Results: Transferrin isoelectrofocusing revealed a typical CDG type I pattern. No other pathological biochemical result was found. A gene panel sequence analysis (test of 102 genes of Congenital Disorders of Glycosylation) was made. Two heterozygous likely pathogenic variants in trans configuration were identified in ALG1, c.826C>T (p.Arg276Trp) and c.863-2A>G. Conclusion: Family was counseled and ketogenic diet was started. She improves her refractory epilepsy and repetitive epileptic status and she is free of seizures. CDGs should be suspect in patients with microcephaly, neurologic involvement and liver compromise. Molecular panels are a rapid and accurate tool for diagnosis and should be consider early in the diagnostic workup. CONICET, FONCyT, UCC