805 Congenital disorder of glycosylation with fibular hemimelia

Abstract

<h3>Background</h3> Congenital disorders of glycosylation (CDG) are a group of hereditary diseases characterized by the deficiency of enzymes involved in proteins glycosylation. CDG are multisystem diseases, caused by more than 140 different genetic defects in glycoprotein and glycolipid glycan synthesis. The most known CDG is PMM2-CDG, in which the genetic defect leads to the loss of phosphomannomutase 2 (PMM2), the enzyme that catalyzes the conversion of mannose-6-phosphate into mannose-1-phosphate. Fibular hemimelia is also a congenital lower extremity anomaly characterized by complete or partial absence of the fibula. This deformity may consist of only fibular shortening or maybe together with femur, tibia, ankle, and foot deformities. Although rare in occurrence, it is the most common congenital absence of long bone of the extremities. Fibular hemimelia is usually an isolated anomaly and occurs sporadically. However, in our case, it occurred together with congenital disorders of glycosylation. <h3>Objectives</h3> We aim to share the clinical features of a patient diagnosed with congenital disorders of glycosylation which has fibular hemimelia and contribute to an increase in the awareness of this disease group. <h3>Methods</h3> The Illumina Trustight One Sequencing Panel was used for sequencing over 4800 genes known to be associated with a clinical phenotype and spanning 12 Mb of genomic content. The panel studied contains 125,000 probes based on the NCBI37/hg19 human reference genome. X-ray and MRI imaging were performed for fibular hemimelia. <h3>Results</h3> The patient was born by elective cesarean section at 38 weeks with 2805 grams. He was the fourteenth pregnancy and ninth living baby of the 32-year-old mother. The infant’s birth length was 45 cm, and the head circumference at birth was 35 cm. Physical examination of the patient revealed medial angulation in the right lower extremity from the knee, clubfoot deformity in the foot, and polydactyly in the left foot. There was no associated facial dysmorphism nor other associated anomalies apart from polydactyly. Abdominal, hip, and transfontanel USG and echocardiography were normal. Fibular hemimelia was found in the patient on x-ray and MR imaging. PMM2 and MEFV gene mutations were found in the gene analysis. The patient was consulted to the orthopedic unit. Although limb amputation was recommended by surgeons, we investigated possible alternatives. As a result, the patient was referred to an external center for a tibial lengthening procedure. <h3>Conclusions</h3> Congenital disorders of glycosylation are a group of hereditary diseases and they may present with different extremity anomalies.