THREE SIBLINGS WITH EXT1-CDG Ezgü Fatih Suheyl 1 , Kasapkara Çiğdem Seher 1 , Okur İlyas 1 , Küçükçongar Aynur 1 , Tümer Leyla 1 , Okur Arzu 2 , Saraç Avni 2 , Wuyts Wim 3 , Hul Els Van 3 , Hasanoğlu Alev 1 1 Div Metab Dis, Gazi University Hospital, Ankara, Turkey 2 Div Ped oncology, Gazi Univ Hospital, Ankara, Turkey 3 Dep Med Genetics,Univ Hosp of Antwerp, Edegem, Belgium EXT1/EXT2-CDG (HME, hereditary multiple osteochondroma) are common defects of O-glycosylation. HME is a rare autosomal dominant disorder characterized by the occurence of multiple benign cartilage capped tumors, that are typically located at juxta-epiphyseal regions of long bones. The diagnostic criteria are at least two osteochondromas of the juxta-epiphyseal region of long bones within the majority of cases with a positive family history and/or mutation in one of the EXT genes. Herein we report three siblings with an age range of 9-14 years who respectively manifested the features of hereditary multiple exostoses. HME affected siblings were referred to outpatient clinic with a lower lumbar spine BMD (z scores of −1.66, -1,9 and −3.18 respectively) and painless progressively increasing bony swellings located at the juxta-epiphyseal regions of long bones as well as other sites. A mutation in EXT1, c.1659 delC (p. Tyr553X), which cosegregated with the disease phenotype, was detected in three siblings. The EXT-1 gene may have a possible additional role in bone metabolism and we should follow these patients not only for the malignant change of exostoses but also for the other complications such as reduction in skeletal growth, restricted joint motion, premature osteoarthrosis and compression of peripheral nerves. Background: DPAGT1-CDG (CDG-Ij) is caused by a deficiency of the first GlcNAc transferase in the ER N-glycosylation pathway. Only one patient has been reported with microcephaly, dysmorphia, exotropia, hypotonia and seizures. Case report: The boy born as the second dizygotic twin by Caesarean section with BW 1410 g and asphyxia. Respiratory distress with frequent apnoeas occurred since birth. Physical examination showed a hypotrophic child with bilateral cataract, cryptorchism, dysmorphia, extremities hypertonia and joint contractures. During the first 3 months: jaundice treated by phototherapy, persistent anaemia-frequent transfusions, feeding difficulties-parenteral and naso-gastric feeding. Then refractory tonic seizures appeared, apnoeas and respiratory insufficiency. Cataract surgery (pars plana lensectomy) at 6 months showed calcification of lenses nuclei. Chest X-ray revealed broncho-pulmonary dysplasia. Biochemical tests showed low serum total protein, mildly elevated aminotransferases and elongated APTT. Metabolic work-up revealed abnormal, type 1 profile of transferrin isoforms suggesting CDG. Activities of PMM, PMI and LLO profile in fibroblasts were normal and patient was classified as unsolved CDG-Ix. He died at age of 2.5 years due to respiratory insufficiency. Genetic defect has been recently identified by whole-exome-sequencing. Conclusions: Congenital cataract is an uncommon manifestation of CDG and a novel finding is calcified nuclear cataract.