A new case of SLC35A2-CDG with a relatively mild phenotype and the experience of D-galactose treatment Katrin Õunap1,2, Mari-Anne Vals 1,2,3, Sander Pajusalu1,4, Dirk Lefeber5, Eva Morava6,7, Tiia Reimand 1,2,4 1Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia, 2Department of Pediatrics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia, 3Children’s Clinic, Tartu University Hospital, Tartu, Estonia, 4Institute of Biomedicine and Translational Medicine, Department of Biomedicine, University of Tartu, Tartu, Estonia, 5 Radboud University Medical Center, Nijmegen, The Netherlands, 6 Hayward Genetics Center, Tulane University Medical School, New Orleans, USA, 7 Universiteit Ziekenhuis Leuven, Leuven, Belgium INTRODUCTION: Congenital disorders of glycosylation (CDG) are a group of hereditary metabolic diseases characterized by abnormal glycosylation of proteins and lipids. We describe here a new case with a defect of the UDP-galactose transporter, encoded by SLC35A2, in the Golgi apparatus and our experience with the treatment. CASE REPORT: He was born at term. In the first year delayed developmental milestones were noticed. First he was consulted at the age of 17m due to craniosynostosis (premature closure of sutura sagittalis superior) (Fig 1b). He had developmental delay, short stature (-3 SD), facial dysmorphism (Fig. 1a) and muscular hypotonia. Brain MRI showed symmetric hyperintense signals in basal ganglia (Fig. 1c), which raised a suspicion of Leigh syndrome. a c b Fig 1: (a) Facial view at 22m of age, note facial dysmorphism; (b) X-ray of the skull, note craniosynostosis; (c) brain MRI, note hyperintense signals in basal ganglia. METHODS AND RESULTS: Transferrin isoelectric focusing analysis for CDG screening showed abnormal type II profile (Fig. 2). Isofocusing of plasma apolipoprotein CIII did not show any abnormalities. Transferrin QTOF mass-spectrometry analysis in two independent samples showed a prominent loss of one sialic acid (21%, norm <5-6%) and several minor glycan peaks showing lack of galactose and sialic acid as seen in SLC35A2-CDG. The loss of one sialic acid could not be explained by secondary causes. Exome sequencing analysis revealed a hemizygous de novo mutation c.670C>T (p.Leu224Phe) in the SLC35A2 gene. Fig 2: TIEF analysis showed abnormal type II profile, which normalized during treatment. Fig 3: Transferrin QTOF mass-spectrometry analysis showed a prominent loss of one sialic acid and several minor glycan peaks showing lack of galactose and sialic acid. Nov 2015 Jan 2016 March 2016 April 2016 Aug 2016 Glycose (mmol/L) 3.5 4.7 4.9 Lactate (mmol/L) 1.3 1.2 1.8 1.6 ALAT (<39 U/L) 13 23 16 18 20 ASAT (<56 U/L) 71 77 80 66 88 Cholesterol (2.2-4.7 mmol/L) 2.1 3.3 2.6 1.7 2.8 Antithrombin III (101-131%) 87 106 99 116 104 IX factor (44-127%) 129 108 118 109 120 INR (0.92-1.14)  1.04 0.96 0.93 0.89 1.05 PT(>70%) 91 112  120  137 90 TSH (0.7-5.97 mU/L) 2.21 4.02 3.97 1.97 3.41 FSH (<3 U/L) - 0.7 0.8  0.6 1.1 LH (<0.1 U/L) 0.16 0.13  <0.1 Thyreoglobulin (9-67 µg/L) 83.53 88.34 82.14 73.2 92.54 Galactose in urine (0-31.5 mmol/mol cr 56.3 2.5 251.6 4 0.5 Table 1: Results of biochemical analysis before treatment in November 2015 and during 9 months of treatment (red color signifies abnormal values). TREATMENT: Treatment with D-galactose was started at 2.5y (1.5 mg/kg/day). We have noticed the normalization of coagulation factors, galactose excretion and transferrin glycosylation (Table 1). Subhepatic fluid disappeared on ultrasaound. EEG has been normal. He is growing well (3 cm during last 10m); he is more active and bright. Craniosynostosis has not progressed during evaluation period. CONCLUSIONS: We describe the use of dietary galactose supplementation in a patient with SLC35A2-CDG defect and we noticed some effect. Still, for definite conclusions, longer evaluation period and larger group of patients are needed. ACKNOWLEDGMENTS: We thank the family for their kind cooperation. This work was supported by the Estonian Research Council grant PUT355.