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Congenital Disorders of Glycosylation

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Congenital Disorders of Glycosylation Why Choose EGL? • EGL offers the most comprehensive CDG testing and is the only lab offering both N-glycan structural and O-glycan analyses • Oligosaccharides analyzed by a more specific methodology than others Test Code Test Name CPT®** Code(s) Congenital Disorders of Glycosylation: Panel, Carbohydrate BCDGP 82373 (x2), 83788 (x1), 84375 (x1) Deficient Transferrin Analysis and N-Glycan Profile, Plasma Congenital Disorders of Glycosylation: N-Glycan Profile, Qualitative, BNGLY 82373 (x1), 83788 (x1), 84375 (x1) Plasma Congenital Disorders of Glycosylation: O-glycan Analysis, BOGLY 82544 (x1), 83788 (x1), 84378 (x1) Quantitative and Qualitative, Plasma Oligosaccharidosis and Congenital Disorders of Glycosylation: High OS 82544 (x1), 82570 (x1), 84377 (x1) resolution Oligosaccharide (Free Glycan) Profile, Urine MCDG1 Congenital Disorders of Glycosylation: Sequencing Panel 81404 (x1), 81405 (x1), 81406 (x1) DCDG1 Congenital Disorders of Glycosylation: Deletion/Duplication Panel 81228 (x1), 81479 (x1) EXOME Medical EmExome: Exome Sequencing, Proband Only 81415 (x1) EXOMT Medical EmExome: Exome Sequencing, Family Trios 81415 (x1), 81416 (x1) **CPT® is a registered trademark of the American Medical Association. Congenital Disorders of Glycosylation For more information about EGL and the nearly 1100 tests we offer: EMAIL CALL WEB [email protected] 404-778-8499 www.geneticslab.emory.edu About Emory Genetics Laboratory (EGL) Biochemical Tests EGL specializes in genetic diagnostic testing, with 45 years of clinical experience and board-certified laboratory Carbohydrate Deficient Transferrin Analysis directors and genetic counselors reporting out cases. EGL offers a combined 1100 molecular genetics, biochemical Methodology: Affinity Chromatography and MALDI TOF/TOF genetics, and cytogenetics tests under one roof and custom testing for all medically relevant genes, for domestic • This analysis is recommended as the first step for CDG screening and international clients. Equally important to improving patient care through quality genetic testing is the contribution EGL makes back to the N-Glycan Structural Analysis scientific and medical communities. EGL is one of only a few clinical diagnostic laboratories to openly share data with Methodology: MALDI TOF/TOF the NCBI freely available public database ClinVar (>7000 variants on >500 genes) and is also the only laboratory with a • N-glycan structural analysis complements the transferrin analysis with increased sensitivity and specificity. free online database (EmVClass), featuring a variant classification search and report request interface, which facilitates The analysis detects N-linked glycans released from total plasma or serum proteins, allowing for a diagnosis of rapid interactive curation and reporting of variants. various types of CDG Congenital Disorders of Glycosylation O-glycan Profile and Quantification EGL provides the most comprehensive testing available for the evaluation of congenital disorders of glycosylation (CDG) Methodology: MALDI TOF/TOF and LC MS/MS and offers complementary DNA testing to confirm all biochemical CDG test results. CDG are the result of alterations in • This test is recommended to screen for mixed type CDGs and O-glycosylation disorders protein and lipid glycosylation, and are genetic in origin. Glycosylation is the process whereby sugars (glycans) are linked together in a specific pattern and attached to proteins and lipids. Glycans signal proper cellular localization of proteins Oligosaccharide and Glycan Screen, Urine and lipids, and are needed for normal function and growth of all tissues and organs in the human body. Methodology: MALDI TOF/TOF • This high resolution oligosaccharide analysis can be used to diagnose CDG-IIb, and potentially identify other CDG phenotypes are extremely variable, with symptoms ranging from severe developmental delay and hypotonia underlying conditions beginning in infancy, to hypoglycemia and protein-losing enteropathy with normal development. CDG-Ia is the most common form reported, due to a deficiency in phosphomannomutase, an enzyme that converts mannose-6-phosphate CDG Next Generation Sequencing (NGS) Panel to mannose-1-phosphate. CDG-Ib (phosphomannose isomerase deficiency) may be treated with the administration of EGL offers the CDG Next Generation Sequencing Panel to aid in the diagnosis of a variety of potential disorders, when a oral mannose. CDG-Ib is the only form of CDG with an available treatment. CDG is suspected. This panel is ideal if the gene mutation is unknown and therefore single-gene analysis won’t be cost- effective. The panel includes an analysis of 66 genes. Consider CDG in all patients with: • Failure to thrive • Perinatal dysmophism • Recurrent infections • Intellectual disability • Microcephaly • Thrombocytopenia • Hypotonia • Loose, wrinkled skin • Developmental delay Genes Included on CDG NGS Panel* • • • Hypoglycemia Abnormal fat pads Coagulopathy ALG1 ALG12 B4GALT7 COG5 DPAGT1 GALNT3 MOGS PIGM RFT1 ST3GAL5 • Cerebellar hypoplasia • Skeletal abnormalities • Hydrops fetalis ALG2 ALG13 CHST14 COG6 DPM1 GFPT1 MPDU1 PIGO SEC23B TMEM165 • Partial thyroxine-binding globulin • Liver dysfunction • Seizures and stroke-like episodes deficiency • A non-specific presentation ALG3 ALG14 CHST3 COG7 DPM3 GNE MPI PIGV SLC35A1 TUSC3 ALG6 ATP6V0A2 CHST6 COG8 EXT1 LARGE NGLY1 PMM2 SLC35C1 The Path to a CDG Diagnosis ALG8 B3GALTL CHSY1 DDOST EXT2 LFNG PGM1 POMGNT1 SLC35D1 Suspected CDG ALG9 B3GAT3 COG1 DHDDS FKRP MAN1B1 PIGA POMT1 SRD5A3 ALG11 B4GALT1 COG4 DOLK FKTN MGAT2 PIGL POMT2 ST3GAL3 N-Glycan and Carbohydrate Deficient *Please note that deletion/duplication analysis is not completed for all genes in the panel. Some genes on this panel are associated with Transferrin Panel additional phenotypes. All genes on the next generation sequencing panel may be ordered separately. Genes included on panels are subject to change. Please visit Normal, but CDG still suspected Abnormal our website for current panel information. Abnormal Whole Exome Sequencing Oligosaccharide Screening Sequencing Analysis New types of CDG are still being discovered. Medical EmExome testing is recommended when: (1) genetic testing for a and O-Glycan Profile suspected condition has yielded no positive results; (2) traditional diagnostic approaches have proven ineffective; or (3) a 0 or 1 mutations 2 mutations Normal cost effective alternative to whole genome testing is desirable. Exome sequencing has the ability to: (1) identify variants in genes that were not tested due to an atypical clinical presentation; (2) identify clinical cases in which variants from different genes contribute to the different phenotypes in the same patient; and (3) cost-effectively provide a plethora of Deletion/Duplication genetic data. Analysis Consider Another Diagnosis No mutation Mutation(s) identified Diagnosis or Confirmed Consider Research Protocols For visuals of abnormal profiles refer towww.geneticslab.emory.edu/MetabolicProfiles. .
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