Research Publications

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Verberkmoes S, Mazza GL, Edmondson AC, Scaglia F, Horikoshi S, Kuschel B, Janssen MCH, Mousa J, Larson A, Shah R, McDonald G, Sarafoglou K, Berry G, Kozicz T, Lam C, Morava E. Goal attainment in PMM2-CDG: A new approach measuring meaningful clinical outcomes. Mol Genet Metab. 2025 Mar 19;145(1):109087. doi: 10.1016/j.ymgme.2025.109087. Epub ahead of print. PMID: 40121796.

Patient-centered outcomes, including patient-reported outcomes (PROs), are increasingly important in healthcare and to appropriately design clinical trials. Unfortunately using PROs in rare diseases is still limited.

Patients with Phosphomannomutase 2-CDG (PMM2-CDG) have highly variable clinical severity, underscoring the need for personalized outcome measures. We used a so far unexplored, individualized approach, the so called Goal Attainment Scaling (GAS), in our natural history study for CDG, which allowed patients to set and track personal goals over time.

We evaluated 93 PMM2-CDG patients assessing goal achievement prospectively. We also analyzed potential associations between GAS and factors such as age, sex, genetic background, and disease severity measured by the Nijmegen Progression CDG Rating Scale (NPCRS).

The most common goals set by patients were related to mobility (31.5 %) and communication (26.8 %), with additional goals focused on body function (22.8 %) and independence (18.8 %). Of the 68 patients with follow-up data, 23.5 % showed no improvement in their goals, while 20.6 % improved in all three personal goals.

It is very important to note, that there was no significant correlation between NPCRS score changes assessed by medical providers, and GAS improvement. Emphasizing the importance of patient set goals in severity scaling

GAS is a valuable additional outcome measure that ensures clinical improvements are meaningful for patients and their representatives, helping to assess individual goals and overall wellbeing.

Aryal RP, Ramanujan A, Bucci C, Neckelmann C, Heimburg-Molinaro J, Cummings SF, Erger F, Beck BB, Seaver LH, Cummings RD. C1GALT1C1-Associated Mosaic Disorder of Glycosylation in a Female. J Inherit Metab Dis. 2025 Mar;48(2):e70006. doi: 10.1002/jimd.70006.

Alharbi H, Horikoshi S, Jenkins SM, Scaglia F, Lam C, Morava E, Larson A, Edmondson AC. Causes of mortality in the congenital disorders of glycosylation. Mol Genet Metab. 2025 Mar;144(3):109052. doi: 10.1016/j.ymgme.2025.109052. Epub 2025 Feb 4.

Muffels IJJ, Kozicz T, Perlstein EO, Morava E. The Therapeutic Future for Congenital Disorders of Glycosylation. J Inherit Metab Dis. 2025 Mar;48(2):e70011. doi: 10.1002/jimd.70011.

García-Cazorla Á, Morava E, Saudubray JM. "Trafficking Disorders: Phenotypical Similarities and Differences With Other IMDs". J Inherit Metab Dis. 2025 Mar;48(2):e70004. doi: 10.1002/jimd.70004.

Matheny-Rabun C, Mokashi SS, Radenkovic S, Wiggins K, Dukes-Rimsky L, Angel P, Ghesquiere B, Kozicz T, Steet R, Morava E, Flanagan-Steet H. O-GlcNAcylation modulates expression and abundance of N-glycosylation machinery in an inherited glycosylation disorder. Cell Rep. 2024 Nov 26;43(11):114976. doi: 10.1016/j.celrep.2024.114976. Epub 2024 Nov 18.

Muffels IJJ, Sadek M, Kozicz T, Morava E. Assessing age of onset and clinical symptoms over time in patients with heterozygous pathogenic DHDDS variants. J Inherit Metab Dis. 2024 Sep;47(5):935-944. doi: 10.1002/jimd.12769. Epub 2024 Jun 21.

Mayfield JM, Hitefield NL, Czajewski I, Vanhye L, Holden L, Morava E, van Aalten DMF, Wells L. O-GlcNAc transferase congenital disorder of glycosylation (OGT-CDG): Potential mechanistic targets revealed by evaluating the OGT interactome. J Biol Chem. 2024 Sep;300(9):107599. doi: 10.1016/j.jbc.2024.107599. Epub 2024 Jul 24. PMID: 39059494; PMCID: PMC11381892.

O-GlcNAc transferase congenital disorder of glycosylation (OGT-CDG) is an inherited disorder caused by dysfunction of the OGT enzyme that affects a complex process in the body called glycosylation. Pathogenic variants associated with OGT-CDG are thought to disrupt the OGT interactome, which consists of interactions between thousands of proteins.

In this review paper, researchers evaluated the OGT interactome to identify potential mechanistic targets for OGT-CDG studies. The team also discussed clinical features of OGT-CDG and the biochemical effects of mutations.

Authors note that as more OGT variants are characterized and additional patients are identified, it may become possible to identify a set of common alterations in OGT function as well as a core set of clinical features of OGT-CDG, which could help improve diagnosis.

Marquez J, Cech JN, Paschal CR, Dingmann B, Scott AI, Thies JM, Mills MR, Albert CM, Beck AE, Beckman E, Bonkowski ES, Earl DL, Lam CT, Mefford HC, Merritt JL 2nd, Nelson Z, Ohlsen TJ, Taylor MR, Perlman SJ, Rudzinski ER, Sikes MC, Waligorski N, Wenger TL, Adam MP, Mirzaa GM, Bennett JT, Glass IA, Sternen DL, Miller DE. Clinical RNA sequencing clarifies variants of uncertain significance identified by prior testing. Genet Med Open. 2024;2:101886. doi: 10.1016/j.gimo.2024.101886. Epub 2024 Aug 9. PMID: 39484203; PMCID: PMC11526042.

RNA sequencing (RNA-seq) is a technique used to evaluate the sequence and quantity of messenger RNA, which can provide insights on gene expression. Although RNA-seq can help identify pathogenic variants in individuals with suspected genetic conditions, technological complexities and limited experience might affect its use in clinical practice.

In this study, researchers evaluated the use of RNA-seq to clarify variants of uncertain significance (VUS) in a clinical setting. The team developed a process to identify individuals who might benefit from clinical RNA-seq. Over a two-year period, genetics providers referred 26 cases for clinical RNA-seq, of which nine cases met the criteria for sequencing.

Results show that clinical RNA-seq was useful in clarifying uncertain results in about one-third of cases, including a new diagnosis of NGLY1 congenital disorder of deglycosylation. Authors note that demonstrating the clinical utility of RNA-seq may improve access to this new testing technique.

Sidpra J, Sudhakar S, Biswas A, Massey F, Turchetti V, Lau T, Cook E, Alvi JR, Elbendary HM, Jewell JL, Riva A, Orsini A, Vignoli A, Federico Z, Rosenblum J, Schoonjans AS, de Wachter M, Delgado Alvarez I, Felipe-Rucián A, Haridy NA, Haider S, Zaman M, Banu S, Anwaar N, Rahman F, Maqbool S, Yadav R, Salpietro V, Maroofian R, Patel R, Radhakrishnan R, Prabhu SP, Lichtenbelt K, Stewart H, Murakami Y, Löbel U, D'Arco F, Wakeling E, Jones W, Hay E, Bhate S, Jacques TS, Mirsky DM, Whitehead MT, Zaki MS, Sultan T, Striano P, Jansen AC, Lequin M, de Vries LS, Severino M, Edmondson AC, Menzies L, Campeau PM, Houlden H, McTague A, Efthymiou S, Mankad K. The clinical and genetic spectrum of inherited glycosylphosphatidylinositol deficiency disorders. Brain. 2024 Aug 1;147(8):2775-2790. doi: 10.1093/brain/awae056.

Zemet R, Hope KD, Edmondson AC, Shah R, Patino M, Yesso AM, Berger JH, Sarafoglou K, Larson A, Lam C, Morava E, Scaglia F. Cardiomyopathy, an uncommon phenotype of congenital disorders of glycosylation: Recommendations for baseline screening and follow-up evaluation. Mol Genet Metab. 2024 Aug;142(4):108513. doi: 10.1016/j.ymgme.2024.108513. Epub 2024 Jun 13.

Bosnyak I, Sadek M, Ranatunga W, Kozicz T, Morava E. Normal transferrin glycosylation does not rule out severe ALG1 deficiency. JIMD Rep. 2024 Apr 16;65(3):135-143. doi: 10.1002/jmd2.12415. eCollection 2024 May.

Lam C, Scaglia F, Berry GT, Larson A, Sarafoglou K, Andersson HC, Sklirou E, Tan QKG, Starosta RT, Sadek M, Wolfe L, Horikoshi S, Ali M, Barone R, Campbell T, Chang IJ, Coles K, Cook E, Eklund EA, Engelhardt NM, Freeman M, Friedman J, Fu DYT, Botzo G, Rawls B, Hernandez C, Johnsen C, Keller K, Kramer S, Kuschel B, Leshinski A, Martinez-Duncker I, Mazza GL, Mercimek-Andrews S, Miller BS, Muthusamy K, Neira J, Patterson MC, Pogorelc N, Powers LN, Ramey E, Reinhart M, Squire A, Thies J, Vockley J, Vreugdenhil H, Witters P, Youbi M, Zeighami A, Zemet R, Edmondson AC, Morava E. Frontiers in congenital disorders of glycosylation consortium, a cross-sectional study report at year 5 of 280 individuals in the natural history cohort. Mol Genet Metab. 2024 Jun 6;142(4):108509. doi: 10.1016/j.ymgme.2024.108509. Epub ahead of print. PMID: 38959600.

Congenital disorders of glycosylation (CDG) are a large group of rare, inherited disorders that affect a complex process in the body called glycosylation. Because the many different types of CDG are rare and vary widely, not much is known about the progression of this group of disorders.

In this study, researchers are exploring the natural history of CDG. The team is gathering data from 280 individuals with CDG across 9 clinical sites. Now at year 5 of the study, the team is sharing an overview of participant characteristics.

Initial findings include insights on liver function, patient-reported outcomes, and neurological features, as well as information on ultra-rare genetic causes of CDG. Authors note that this study serves as an important resource to build future research studies, improve clinical care, and prepare for clinical trial readiness.

Shah R, Eklund EA, Radenkovic S, Sadek M, Shammas I, Verberkmoes S, Ng BG, Freeze HH, Edmondson AC, He M, Kozicz T, Altassan R, Morava E. ALG13-Congenital Disorder of Glycosylation (ALG13-CDG): Updated clinical and molecular review and clinical management guidelines. Mol Genet Metab. 2024 Jun;142(2):108472. doi: 10.1016/j.ymgme.2024.108472. Epub 2024 Apr 23.

Starosta RT, Lee AJ, Toolan ER, He M, Wongkittichote P, Daniel EJP, Radenkovic S, Budhraja R, Pandey A, Sharma J, Morava E, Nguyen H, Dickson PI. D-mannose as a new therapy for fucokinase deficiency-related congenital disorder of glycosylation (FCSK-CDG). Mol Genet Metab. 2024 Jun;142(2):108488. doi: 10.1016/j.ymgme.2024.108488. Epub 2024 May 9.

Budhraja R, Radenkovic S, Jain A, Muffels IJJ, Ismaili MHA, Kozicz T, Pandey A, Morava E. Liposome-encapsulated mannose-1-phosphate therapy improves global N-glycosylation in different congenital disorders of glycosylation. Mol Genet Metab. 2024 Jun;142(2):108487. doi: 10.1016/j.ymgme.2024.108487. Epub 2024 May 7.

Martínez Duncker I, Mata-Salgado D, Shammas I, Ranatunga W, Daniel EJP, Cruz Muñoz ME, Abreu M, Mora-Montes H, He M, Morava E, Zafra de la Rosa G. Case report: Novel genotype of ALG2-CDG and confirmation of the heptasaccharide glycan (NeuAc-Gal-GlcNAc-Man2-GlcNAc2) as a specific diagnostic biomarker. Front Genet. 2024 May 6;15:1363558. doi: 10.3389/fgene.2024.1363558. eCollection 2024.

Daniel EJP, Edmondson AC, Argon Y, Alsharhan H, Lam C, Freeze HH, He M. Deficient glycan extension and endoplasmic reticulum stresses in ALG3-CDG. J Inherit Metab Dis. 2024 Apr 10. doi: 10.1002/jimd.12739. Epub ahead of print. PMID: 38597022.

ALG3-CDG is a rare congenital disorder of glycosylation (CDG) characterized by neurological symptoms, transaminitis (elevated liver enzymes), and frequent infections. When the endoplasmic reticulum—a network of membranes inside a cell that plays a major role in protein synthesis and transport—is under stress, one of the earliest and fastest responses in cells is glycan extension. The first step of this process is catalyzed by the ALG3 enzyme, which is deficient in patients with ALG3-CDG.

In this study, researchers investigated the effects of glycan extension deficiency in ALG3-CDG. The team explored the biochemical consequences of this deficiency and associated response to endoplasmic reticulum stress.

These results provide a better understanding of how glycan extension deficiency affects patients with ALG3-CDG. Authors note that these findings also have important implications for the development of personalized medicine for other types of CDG.

Garapati K, Budhraja R, Saraswat M, Kim J, Joshi N, Sachdeva GS, Jain A, Ligezka AN, Radenkovic S, Ramarajan MG, Udainiya S, Raymond K, He M, Lam C, Larson A, Edmondson AC, Sarafoglou K, Larson NB, Freeze HH, Schultz MJ, Kozicz T, Morava E, Pandey A. A complement C4-derived glycopeptide is a biomarker for PMM2-CDG. JCI Insight. 2024 Apr 8;9(7):e172509. doi: 10.1172/jci.insight.172509.

Budhraja R, Joshi N, Radenkovic S, Kozicz T, Morava E, Pandey A. Dysregulated proteome and N-glycoproteome in ALG1-deficient fibroblasts. Proteomics. 2024 Mar 12:e2400012. doi: 10.1002/pmic.202400012. Epub ahead of print. PMID: 38470198.

ALG1-congenital disorder of glycosylation (ALG1-CDG) is an inherited disorder caused by variants in the ALG1 gene. These variants affect N-glycosylation, which is the body’s process of creating, changing, and attaching sugar blocks to proteins and lipids. However, not much is known about how these variants affect the cellular proteome (proteins expressed in cells) and the process of glycosylation.

In this study, researchers explored proteomics and N-glycoproteomics in ALG1-CDG. The team studied fibroblasts (connective tissue cells) from three individuals with different ALG1 variants.

Results revealed altered protein levels and a reduction of mature forms of glycopeptides. Authors note that these results can help us understand the biology and molecular mechanisms of ALG1-CDG, differentiate CDG types, and identify potential biomarkers.

Radenkovic S, Budhraja R, Klein-Gunnewiek T, King AT, Bhatia TN, Ligezka AN, Driesen K, Shah R, Ghesquière B, Pandey A, Kasri NN, Sloan SA, Morava E, Kozicz T. Neural and metabolic dysregulation in PMM2-deficient human in vitro neural models. Cell Rep. 2024 Mar 1;43(3):113883. doi: 10.1016/j.celrep.2024.113883. Epub ahead of print. PMID: 38430517.

PMM2-congenital disorder of glycosylation (PMM2-CDG) is an inherited condition caused by mutations in the PMM2 gene. Most individuals with PMM2-CDG experience neurological symptoms. However, not much is known about the specific brain-related changes caused by PMM2 deficiency.

In this study, researchers explored the neurological characteristics of PMM2-CDG using human in vitro neural models. The team created human induced pluripotent stem cell (hiPSC)-derived neural models to observe changes in neural function and metabolic dynamics.

Results revealed disrupted functioning of PMM2-deficient neuronal networks, as well as widespread changes in metabolite composition, RNA expression, protein abundance, and protein glycosylation. Authors note that these findings introduce potentially critical factors contributing to the early neural issues in patients with PMM2-CDG, paving the way for exploring innovative treatment approaches.

Madan-Khetarpal S, He M, Wongkittichote P, Dobrowolski SF. Congenital Disorder of Glycosylation in a Child with Macrosomia. Clin Chem. 2023 Dec 1;69(12):1432-1434. doi: 10.1093/clinchem/hvad166.

Muthusamy K, Perez-Ortiz JM, Ligezka AN, Altassan R, Johnsen C, Schultz MJ, Patterson MC, Morava E. Neurological manifestations in PMM2-congenital disorders of glycosylation (PMM2-CDG): Insights into clinico-radiological characteristics, recommendations for follow-up, and future directions. Genet Med. 2023 Nov 10;26(2):101027. doi: 10.1016/j.gim.2023.101027. Online ahead of print.

Duan R, Marafi D, Xia ZJ, Ng BG, Maroofian R, Sumya FT, Saad AK, Du H, Fatih JM, Hunter JV, Elbendary HM, Baig SM, Abdullah U, Ali Z, Efthymiou S, Murphy D, Mitani T, Withers MA, Jhangiani SN, Coban-Akdemir Z, Calame DG, Pehlivan D, Gibbs RA, Posey JE, Houlden H, Lupashin VV, Zaki MS, Freeze HH, Lupski JR. Biallelic missense variants in COG3 cause a congenital disorder of glycosylation with impairment of retrograde vesicular trafficking. J Inherit Metab Dis. 2023 Nov;46(6):1195-1205. doi: 10.1002/jimd.12679. Epub 2023 Oct 5.

Altassan R, Allers MM, De Graef D, Shah R, de Vries M, Larson A, Glamuzina E, Morava E. Defining the phenotype of PGAP3-congenital disorder of glycosylation; a review of 65 cases. Mol Genet Metab. 2023 Nov;140(3):107688. doi: 10.1016/j.ymgme.2023.107688. Epub 2023 Aug 23.

Del Caño-Ochoa F, Ng BG, Rubio-Del-Campo A, Mahajan S, Wilson MP, Vilar M, Rymen D, Sánchez-Pintos P, Kenny J, Martos ML, Campos T, Wortmann SB, Freeze HH, Ramón-Maiques S. Beyond genetics: Deciphering the impact of missense variants in CAD deficiency. J Inherit Metab Dis. 2023 Nov;46(6):1170-1185. doi: 10.1002/jimd.12667. Epub 2023 Sep 11.

CAD deficiency is a rare congenital disorder of glycosylation characterized by epileptic encephalopathy (disease affecting the brain). Because symptoms are non-specific, there is no biomarker, and the CAD protein has over 1,000 known variants, CAD deficiency is difficult to diagnose.

In this study, researchers aimed to improve diagnosis of CAD deficiency. The team assessed the disease-causing ability of both previously reported and unreported CAD variants. Additionally, researchers studied the impact of disease-causing variants at the protein level.

Authors note that combining these functional and protein structural analysis methods can help refine clinical diagnostic workflow for CAD variants.

Starosta RT, Kerashvili N, Pruitt C, Schultz MJ, Boyer SW, Morava E, Lasio MLD, Grange DK. PIGO-CDG: A case study with a new genotype, expansion of the phenotype, literature review, and nosological considerations. JIMD Rep. 2023 Sep 20;64(6):424-433. doi: 10.1002/jmd2.12396. eCollection 2023 Nov.

Wang R, Helbig I, Edmondson AC, Lin L, Xing Y. Splicing defects in rare diseases: transcriptomics and machine learning strategies towards genetic diagnosis. Brief Bioinform. 2023 Sep 20;24(5):bbad284. doi: 10.1093/bib/bbad284. PMID: 37580177; PMCID: PMC10516351

Many rare diseases are caused by genomic variants that affect the process of pre-messenger RNA splicing and its regulation. However, these splice-altering variants are often overlooked by common workflows for genetic diagnosis and clinical variant interpretation.

In this review, researchers summarized recent developments and challenges in using RNA sequencing technologies to investigate rare diseases. Discussion included the use of new computational splicing prediction tools to reveal splice-altering variants.

Authors predict that continuous improvements to sequencing technologies and predictive modeling will expand our understanding of splicing regulation and improve diagnoses for rare disease patients.

Monticelli M, D'Onofrio T, Jaeken J, Morava E, Andreotti G, Cubellis MV. Congenital disorders of glycosylation: narration of a story through its patents. Orphanet J Rare Dis. 2023 Aug 29;18(1):247. doi: 10.1186/s13023-023-02852-w.

Hong X, Edmondson AC, Strong A, Pomerantz D, Michl E, Berry G, He M. Combined PMM2-CDG and hereditary fructose intolerance in a patient with mild clinical presentation. Mol Genet Metab. 2023 Aug 9;140(3):107682. doi: 10.1016/j.ymgme.2023.107682. Online ahead of print.

Ligezka AN, Budhraja R, Nishiyama Y, Fiesel FC, Preston G, Edmondson A, Ranatunga W, Van Hove JLK, Watzlawik JO, Springer W, Pandey A, Morava E, Kozicz T. Interplay of Impaired Cellular Bioenergetics and Autophagy in PMM2-CDG. Genes (Basel). 2023 Aug 4;14(8):1585. doi: 10.3390/genes14081585. PMID: 37628636; PMCID: PMC10454768

PMM2-CDG is a type of congenital disorder of glycosylation caused by mutations in the PMM2 gene. Some types of CDG are associated with dysfunction of the mitochondria, which generate energy to power cells. However, not much is known about cellular bioenergetics (how cells transform energy) in PMM2-CDG.

In this study, researchers evaluated mitochondrial function and autophagy (the process of breaking down cellular contents) in PMM2-CDG. The team evaluated fibroblasts (skin cell-derived connective tissue cells) with different genotypes from a natural history study of individuals with PMM2-CDG.

Results reveal secondary mitochondrial dysfunction in PMM2-CDG, as well as altered autophagy, which may act as a marker of disease severity. Authors note that manipulating these processes could offer therapeutic benefits when combined with existing treatments for PMM2-CDG.

Radenkovic S, Ligezka AN, Mokashi SS, Driesen K, Dukes-Rimsky L, Preston G, Owuocha LF, Sabbagh L, Mousa J, Lam C, Edmondson A, Larson A, Schultz M, Vermeersch P, Cassiman D, Witters P, Beamer LJ, Kozicz T, Flanagan-Steet H, Ghesquière B, Morava E. Tracer metabolomics reveals the role of aldose reductase in glycosylation. Cell Rep Med. 2023 Jun 20;4(6):101056. doi: 10.1016/j.xcrm.2023.101056. Epub 2023 May 30.

De Graef D, Ligezka AN, Rezents J, Mazza GL, Preston G, Schwartz K, Krzysciak W, Lam C, Edmondson AC, Johnsen C, Kozicz T, Morava E. Coagulation abnormalities in a prospective cohort of 50 patients with PMM2-congenital disorder of glycosylation. Mol Genet Metab. 2023 Jun;139(2):107606. doi: 10.1016/j.ymgme.2023.107606. Epub 2023 May 9.

Shah R, Johnsen C, Pletcher BA, Edmondson AC, Kozicz T, Morava E. Long-term outcomes in ALG13-Congenital Disorder of Glycosylation. Am J Med Genet A. 2023 Jun;191(6):1626-1631. doi: 10.1002/ajmg.a.63179. Epub 2023 Mar 17.

Sitek A, Ligezka A, Budhraja R, Morava E, Chiarella SE. Pathogenic DDOST Variant Is Associated with Humoral Immune Deficiency. J Clin Immunol. 2023 May;43(4):692-694. doi: 10.1007/s10875-023-01429-3. Epub 2023 Jan 12.

Tahata S, Weckwerth J, Ligezka A, He M, Lee HE, Heimbach J, Ibrahim SH, Kozicz T, Furuya K, Morava E. Liver transplantation recovers hepatic N-glycosylation with persistent IgG glycosylation abnormalities: Three-year follow-up in a patient with phosphomannomutase-2-congenital disorder of glycosylation. Mol Genet Metab. 2023 Apr;138(4):107559. doi: 10.1016/j.ymgme.2023.107559. Epub 2023 Mar 17.

Alharbi H, Daniel EJP, Thies J, Chang I, Goldner DL, Ng BG, Witters P, Aqul A, Velez-Bartolomei F, Enns GM, Hsu E, Kichula E, Lee E, Lourenco C, Poskanzer SA, Rasmussen S, Saarela K, Wang YM, Raymond KM, Schultz MJ, Freeze HH, Lam C, Edmondson AC, He M. Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects identifies phenotypic association. J Inherit Metab Dis. 2023 Mar;46(2):300-312. doi: 10.1002/jimd.12589. Epub 2023 Jan 29.

Radenkovic S, Laerdahl JK, Backe PH, Morava E. The role of PGM1isoform 2 in PGM1-CDG: One step closer to genotype-phenotype correlation?. J Inherit Metab Dis. 2023 Mar;46(2):159-160. doi: 10.1002/jimd.12601.

Balakrishnan B, Altassan R, Budhraja R, Liou W, Lupo A, Bryant S, Mankouski A, Radenkovic S, Preston GJ, Pandey A, Boudina S, Kozicz T, Morava-Kozicz E, Lai K. AAV-based gene therapy prevents and halts the progression of dilated cardiomyopathy in a mouse model of phosphoglucomutase 1 deficiency (PGM1-CDG). Transl Res. 2023 Jul;257:1-14. doi: 10.1016/j.trsl.2023.01.004. Epub 2023 Jan 26.

Altassan R, Albert-Brotons DC, Alowain M, Al-Halees Z, Jaeken J, Morava E. Successful heart transplantation in an infant with phosphoglucomutase 1 deficiency (PGM1-CDG). JIMD Rep. 2022 Nov 22;64(2):123-128. doi: 10.1002/jmd2.12350. eCollection 2023 Mar.

Sosicka P, Ng BG, Freeze HH. Chemical Therapies for Congenital Disorders of Glycosylation. ACS Chem Biol. 2022 Nov 18;17(11):2962-2971. doi: 10.1021/acschembio.1c00601. Epub 2021 Nov 17.

Mahajan S, Ng BG, AlAbdi L, Earnest PDJ, Sosicka P, Patel N, Helaby R, Abdulwahab F, He M, Alkuraya FS, Freeze HH. Homozygous truncating variant in MAN2A2 causes a novel congenital disorder of glycosylation with neurological involvement. J Med Genet. 2022 Nov 10:jmg-2022-108821. doi: 10.1136/jmg-2022-108821. Epub ahead of print. PMID: 36357165.

Congenital disorders of glycosylation (CDG) are a large group of rare, inherited disorders that affect a complex process in the body called glycosylation. Defects in Golgi enzymes, which play a critical role in N-glycan processing and brain development, are often defined as types of CDG. However, defects in the Golgi enzyme MAN2A2 have not been known to cause defects in glycosylation. In this study, researchers investigated the effects of variants in MAN2A2. In a family of affected individuals, the team performed exome sequencing, analyzed N-glycans, and designed a cell-based complementation assay to evaluate the disease-causing effects of the variant. Findings show that variants in MAN2A2 cause a new type of CDG, which is characterized by neurological involvement and facial dysmorphism. Authors note that the cell-based complementation assay designed in this study can also help diagnose patients with potentially pathogenic variants in a very similar enzyme, MAN2A1.

Elsharkawi I, Wongkittichote P, Daniel EJP, Starosta RT, Ueda K, Ng BG, Freeze HH, He M, Shinawi M. DDOST-CDG. Clinical and molecular characterization of a third patient with a milder and a predominantly movement disorder phenotype. J Inherit Metab Dis. 2022 Oct 10. doi: 10.1002/jimd.12565. Epub ahead of print. PMID: 36214423.

DDOST-CDG is an ultra-rare type of congenital disorder of glycosylation (CDG) that is caused by mutations in the gene DDOST. The metabolic disorder was previously reported in just two patients, whose clinical features included severe developmental delay, failure to thrive, and hypotonia (low muscle tone). Both patients also had abnormal transferrin glycosylation. In this study, researchers describe a new patient with DDOST-CDG. The 18-year-old male presented with moderate developmental delay, progressive opsoclonus (involuntary, rapid eye movements), myoclonus (involuntary, sudden muscle spasms), ataxia (impaired balance or coordination), tremor, and dystonia (involuntary muscle contractions that cause repetitive or twisting movements). The team performed several tests, including biochemical studies, exome sequencing, plasma N-glycan profiling, and western blot analysis, to learn more about the patient’s clinical features. Authors state that these insights—including new findings on the clinical variability, phenotypes, and genotypes of DDOST-CDG—are essential for diagnosing and managing patients with DDOST-CDG.

Sosicka P, Ng BG, Pepi LE, Shajahan A, Wong M, Scott DA, Matsumoto K, Xia ZJ, Lebrilla CB, Haltiwanger RS, Azadi P, Freeze HH. Origin of cytoplasmic GDP-fucose determines its contribution to glycosylation reactions. J Cell Biol. 2022 Oct 3;221(10):e202205038. doi: 10.1083/jcb.202205038. Epub 2022 Sep 2. PMID: 36053214.

Congenital disorders of glycosylation (CDG) are a group of inherited metabolic disorders that affect a process called glycosylation. This process uses monosaccharides (simple sugars) from multiple sources to produce nucleotide sugars (activated forms of monosaccharides). Since these sources of monosaccharides are assumed to contribute to one similar pool, their individual contributions are often overlooked. In this study, researchers explored the hypothesis that fucose (a type of monosaccharide) exists in multiple, distinct pools. The team measured the contribution of fucose from different sources. Findings show that cells identify and select from different pools of fucose for the process of glycosylation. Authors also present new perspectives on monosaccharide metabolism, which may have other applications beyond glycosylation.

Budhraja R, Saraswat M, De Graef D, Ranatunga W, Ramarajan MG, Mousa J, Kozicz T, Pandey A, Morava E. N-glycoproteomics reveals distinct glycosylation alterations in NGLY1-deficient patient-derived dermal fibroblasts. J Inherit Metab Dis. 2022 Sep 14. doi: 10.1002/jimd.12557. Epub ahead of print. PMID: 36102038.

NGLY1-CDDG (congenital disorder of deglycosylation) is a multisystemic, inherited condition caused by a mutation in the NGLY1 gene. Although the NGLY1 enzyme plays an essential role in the process of deglycosylation, the effects of NGLY1 deficiency on protein glycosylation are not yet understood. In this study, researchers explored the hypothesis that NGLY1 deficiency leads to accumulation of misfolded glycoproteins. Using glycoproteomics and proteomics methods, the team analyzed fibroblasts from four patients with NGLY1 deficiency carrying different variants in NGLY1. Results showed no significant accumulation of glycoproteins in the NGLY1-deficient fibroblasts. However, researchers found distinct changes in specific glycoproteins. As the first study of its kind, authors note that these findings highlight new insights for understanding NGLY1-CDDG.

Shimada S, Ng BG, White AL, Nickander KK, Turgeon C, Liedtke KL, Lam CT, Font-Montgomery E, Lourenco CM, He M, Peck DS, Umana LA, Uhles CL, Haynes D, Wheeler PG, Bamshad MJ, Nickerson DA, Cushing T, Gates R, Gomez-Ospina N, Byers HM; UW Center for Mendelian Genomics; Scalco FB, Martinez NN, Sachdev R, Smith L, Poduri A, Malone S, Harris RV, Scheffer IE, Rosenzweig SD, Adams DR, Gahl WA, Malicdan MCV, Raymond KM, Freeze HH, Wolfe LA. Clinical, biochemical and genetic characteristics of MOGS-CDG: a rare congenital disorder of glycosylation. J Med Genet. 2022 Jul 5:jmedgenet-2021-108177. doi: 10.1136/jmedgenet-2021-108177. Online ahead of print.

Albokhari D, Ng BG, Guberinic A, Daniel EJP, Engelhardt NM, Barone R, Fiumara A, Garavelli L, Trimarchi G, Wolfe L, Raymond KM, Morava E, He M, Freeze HH, Lam C, Edmondson AC. ALG8-CDG: Molecular and phenotypic expansion suggests clinical management guidelines. J Inherit Metab Dis.. 2022 Jun 18. doi: 10.1002/jimd.12527. Epub ahead of print. PMID: 35716054.

ALG8-congenital disorder of glycosylation (ALG8-CDG) is a rare, inherited disorder that affects multiple systems in the body. Patients with ALG8-CDG commonly present with decreased muscle tone, intestinal problems, and liver problems. In this study, researchers describe seven new individuals with ALG8-CDG, bringing the total to 26 individuals reported in medical literature. The team diagnosed these patients based on biochemical and molecular testing, identifying nine novel variants in ALG8. The cohort also includes the two oldest patients reported to date. This study expands the phenotype of ALG8-CDG to include stable intellectual disability, autism spectrum disorder, and other neuropsychiatric symptoms. Researchers also expand the clinical features in a variety of organ systems. To improve clinical management, authors suggest a comprehensive evaluation and monitoring strategy.

Geiculescu I, Dranove J, Cosper G, Edmondson AC, Morava-Kozicz E, Carter LB. A rare cause of infantile achalasia: GMPPA-congenital disorder of glycosylation with two novel compound heterozygous variants. Am J Med Genet A. 2022 Jun 4. doi: 10.1002/ajmg.a.62859. Epub ahead of print. PMID: 35665995.

Achalasia is a disorder of the esophagus, the tube that carries food from the mouth to the stomach. It is characterized by enlargement of the esophagus, impaired ability of the esophagus to push food down toward the stomach (peristalsis), and failure of the ring-shaped muscle at the bottom of the esophagus (the lower esophageal sphincter) to relax. Because achalasia is rare in the pediatric population, clinicians should consider associated genetic disorders. This includes GMPPA-congenital disorder of glycosylation (CDG), a rare type of CDG that is caused by variants in the GMPPA gene. In this study, researchers describe a 9-month-old female with achalasia and alacrima (reduced or absent ability to produce tears). The patient was found to have two novel compound heterozygous variants in the GMPPA gene that are associated with GMPPA-CDG. Authors provide a brief review of GMPPA-CDG, including management of this condition.

Ritter AL, Gold J, Hayashi H, Ackermann AM, Hanke S, Skraban C, Cuddapah S, Bhoj E, Li D, Kuroda Y, Wen J, Takeda R, Bibb A, El Chehadeh S, Piton A, Ohl J, Kukolich MK, Nagasaki K, Kato K, Ogi T, Bhatti T, Russo P, Krock B, Murrell JR, Sullivan JA, Shashi V, Stong N, Hakonarson H, Sawano K, Torti E, Willaert R, Si Y, Wilcox WR, Wirgenes KV, Thomassen K, Carlotti K, Erwin A, Lazier J, Marquardt T, He M, Edmondson AC, Izumi K. Expanding the phenotypic spectrum of ARCN1-related syndrome. Genet Med. 2022 Jun;24(6):1227-1237. doi: 10.1016/j.gim.2022.02.005. Epub 2022 Mar 14.

Boyer SW, Johnsen C, Morava E. Nutrition interventions in congenital disorders of glycosylation. Trends Mol Med. 2022 Jun;28(6):463-481. doi: 10.1016/j.molmed.2022.04.003. Epub 2022 May 10.

Ligezka AN, Mohamed A, Pascoal C, Ferreira VDR, Boyer S, Lam C, Edmondson A, Krzysciak W, Golebiowski R, Perez-Ortiz J, Morava E. Patient-reported outcomes and quality of life in PMM2-CDG. Mol Genet Metab. 2022 Jun;136(2):145-151. doi: 10.1016/j.ymgme.2022.04.002. Epub 2022 Apr 20.

Freeze HH, Jaeken J, Matthijs G. CDG or not CDG. J Inherit Metab Dis.. 2022 May;45(3):383-385. doi: 10.1002/jimd.12498. Epub 2022 Apr 1. PMID: 35338706; PMCID: PMC9121739.

In this letter to the editor, an expert team of authors explores a consensus on which genetic conditions should be identified as congenital disorders of glycosylation (CDG). “They are aiming to be inclusive; CDG should be used as the correct nomenclature in any disorders where the synthesis of glycans, glycoproteins, or glycolipids—including oligosaccharide transfer, glycan maturation, or trafficking—is affected,” says Eva Morava-Kozicz, MD, PhD, principal investigator of the Frontiers in Congenital Disorders of Glycosylation Consortium (FCDGC). “This is demonstrated by abnormal glycosylation in functional studies, and should be called a CDG.”

Tahata S, Raymond K, Quade M, Barnes S, Boyer S, League S, Kumanovics A, Abraham R, Jacob E, Menon P, Morava E. Defining the mild variant of leukocyte adhesion deficiency type II (SLC35C1-congenital disorder of glycosylation) and response to l-fucose therapy: Insights from two new families and review of the literature. Am J Med Genet A. 2022 Mar 26. doi: 10.1002/ajmg.a.62737. Epub ahead of print. PMID: 35338746.

Leukocyte adhesion deficiency type II (LAD II, also known as SLC35C1-congenital disorder of glycosylation) is an autosomal recessive disorder characterized by growth and cognitive impairment, peripheral neutrophilia, recurrent infections, and the Bombay blood phenotype. Among a subset of patients with a milder presentation, descriptions have also included short stature and developmental delay with minimal immune and hematologic (relating to blood) features. While some patients with LAD II benefit from oral fucose therapy, this has not yet been studied in patients with milder disease. In this study, researchers describe three new patients from two separate families with the milder variant of LAD II and review the published literature. After 27 months of oral fucose supplementation, one patient showed improvements in speech and cognition, CD15 expression, and core fucosylation of serum glycoproteins. Authors note that these patients support classification of this disorder into distinct subtypes—a classical severe and an attenuated variant—and provide preliminary evidence of benefit of fucose therapy in the latter group.

Tiwary H, Hecht LE, Brucker WJ, Berry GT, Rodig NM. The development of end stage renal disease in two patients with PMM2-CDG. JIMD Rep. 2022 Jan 10;63(2):131-136. doi: 10.1002/jmd2.12269. eCollection 2022 Mar.

Hong X, Alharbi H, Albokhari D, Edmondson AC, He M. A 6-Month-Old Infant with Severe Failure to Thrive during COVID-19 Pandemic. Clin Chem. 2022 Jul 3;68(7):987-989. doi: 10.1093/clinchem/hvac012.

Ligezka AN, Radenkovic S, Saraswat M, Garapati K, Ranatunga W, Krzysciak W, Yanaihara H, Preston G, Brucker W, McGovern RM, Reid JM, Cassiman D, Muthusamy K, Johnsen C, Mercimek-Andrews S, Larson A, Lam C, Edmondson AC, Ghesquière B, Witters P, Raymond K, Oglesbee D, Pandey A, Perlstein EO, Kozicz T, Morava E. Sorbitol Is a Severity Biomarker for PMM2-CDG with Therapeutic Implications. Ann Neurol. 2021 Dec;90(6):887-900. doi: 10.1002/ana.26245. Epub 2021 Oct 26.

Vaes L, Rymen D, Cassiman D, Ligezka A, Vanhoutvin N, Quelhas D, Morava E, Witters P Genotype-Phenotype Correlations in PMM2-CDG . Genotype-Phenotype Correlations in PMM2-CDG. Genes (Basel). 2021 Oct 21;12(11):1658. doi: 10.3390/genes12111658. PMID: 34828263; PMCID: PMC8620515.

PMM2-CDG is a rare disease that causes hypoglycosylation of multiple proteins. Direct genotype-phenotype correlations are not yet identified. In this paper, researchers carried out a retrospective cohort study on 26 PMM2-CDG patients. They collected the identified genotype, as well as variables indicating the disease severity and patients' phenotype. By studying the phenotypic effects of patients' genotype, researchers gained a better insight in the phenotypic prognosis of PMM2-CDG, according to their molecular base. They concluded that specific pathogenic variants (p.Pro113Leu and p.Phe119Leu) have a significantly higher total NPCRS disease severity score which indicates a more severe clinical outcome. The Nijmegen Paediatric CDG Rating Scale (NPCRS) is a tool to objectively follow the clinical disease progression in clinical disorders of glycosylation (CDG). Pathogenic variants affecting the folding or stabilization domain of the PMM2 enzyme protein have a significantly lower total NPCRS and thus the genetic results could provide a good prognostic clinical outcome.

Johnsen C, Edmondson AC.. Manifestations and Management of Hepatic Dysfunction in Congenital Disorders of Glycosylation. Clin Liver Dis (Hoboken). 2021 Sep 19;18(2):54-66. doi: 10.1002/cld.1105. eCollection 2021 Aug.

Čechová A, Honzík T, Edmondson AC, Ficicioglu C, Serrano M, Barone R, De Lonlay P, Schiff M, Witters P, Lam C, Patterson M, Janssen MCH, Correia J, Quelhas D, Sykut-Cegielska J, Plotkin H, Morava E, Sarafoglou K. Should patients with Phosphomannomutase 2-CDG (PMM2-CDG) be screened for adrenal insufficiency?. Mol Genet Metab. 2021 Aug;133(4):397-399. doi: 10.1016/j.ymgme.2021.06.003. Epub 2021 Jun 11.

Polla DL, Edmondson AC, Duvet S, March ME, Sousa AB, Lehman A; CAUSES Study, Niyazov D, van Dijk F, Demirdas S, van Slegtenhorst MA, Kievit AJA, Schulz C, Armstrong L, Bi X, Rader DJ, Izumi K, Zackai EH, de Franco E, Jorge P, Huffels SC, Hommersom M, Ellard S, Lefeber DJ, Santani A, Hand NJ, van Bokhoven H, He M, de Brouwer APM. Bi-allelic variants in the ER quality-control mannosidase gene EDEM3 cause a congenital disorder of glycosylation. Am J Hum Genet. 2021 Jul 1;108(7):1342-1349. doi: 10.1016/j.ajhg.2021.05.010. Epub 2021 Jun 17.

Morava E, Schatz UA, Torring PM, Abbott MA, Baumann M, Brasch-Andersen C, Chevalier N, Dunkhase-Heinl U, Fleger M, Haack TB, Nelson S, Potelle S, Radenkovic S, Bommer GT, Van Schaftingen E, Veiga-da-Cunha M. Impaired glucose-1,6-biphosphate production due to bi-allelic PGM2L1 mutations is associated with a neurodevelopmental disorder. Am J Hum Genet. 2021 Jun 3;108(6):1151-1160. doi: 10.1016/j.ajhg.2021.04.017. Epub 2021 May 11.

Study authors describe a genetic syndrome due to PGM2L1 deficiency. The gene PGM2L1 is highly expressed in the brain. They report the identification of four children with PGM2L1 deficiency sharing a largely neurological phenotype. All four children had severe developmental and speech delay, dysmorphic facial features, ear anomalies, high arched palate, strabismus, hypotonia, and keratosis pilaris. Early obesity and seizures were present in three individuals. Study authors concluded that, while analyses indicated PGM2L1 deficiency does not appear to be a glycosylation defect, the discovery of this developmental disorder highlights the importance of glucose-1,6-biophosphate in the brain.

Perales-Clemente E, Liedtke K, Studinski A, Radenkovic S, Gavrilov D, Oglesbee D, Matern D, Rinaldo P, Tortorelli S, Morava E, Raymond K. A new D-galactose treatment monitoring index for PGM1-CDG. J Inherit Metab Dis. 2021 Sep;44(5):1263-1271. doi: 10.1002/jimd.12406. Epub 2021 Jun 22.

Witters P, Andersson H, Jaeken J, Tseng L, van Karnebeek CDM, Lefeber DJ, Cassiman D, Morava E. D-galactose supplementation in individuals with PMM2-CDG: results of a multicenter, open label, prospective pilot clinical trial. Orphanet J Rare Dis. 2021 Mar 20;16(1):138. doi: 10.1186/s13023-020-01609-z.

Alsharhan H, He M, Edmondson AC, Daniel EJP, Chen J, Donald T, Bakhtiari S, Amor DJ, Jones EA, Vassallo G, Vincent M, Cogné B, Deb W, Werners AH, Jin SC, Bilguvar K, Christodoulou J, Webster RI, Yearwood KR, Ng BG, Freeze HH, Kruer MC, Li D, Raymond KM, Bhoj EJ, Sobering AK. ALG13 X-linked intellectual disability: New variants, glycosylation analysis, and expanded phenotypes. J Inherit Metab Dis. 2021 Mar 18. doi: 10.1002/jimd.12378. Online ahead of print.

Witters P, Edmondson AC, Lam C, Johnsen C, Patterson MC, Raymond KM, He M, Freeze HH, Morava E. Spontaneous improvement of carbohydrate-deficient transferrin in PMM2-CDG without mannose observed in CDG natural history study. Orphanet J Rare Dis. 2021 Feb 25;16(1):102. doi: 10.1186/s13023-021-01751-2.

Alsharhan H, Ng BG, Daniel EJP, Friedman J, Pivnick EK, Al-Hashem A, Faqeih EA, Liu P, Engelhardt NM, Keller KN, Chen J, Mazzeo PA; University of Washington Center for Mendelian Genomics (UW-CMG), Rosenfeld JA, Bamshad MJ, Nickerson DA, Raymond KM, Freeze HH, He M, Edmondson AC, Lam C. Expanding the phenotype, genotype and biochemical knowledge of ALG3-CDG. J Inherit Metab Dis. 2021 Feb 13. doi: 10.1002/jimd.12367. Online ahead of print.

Berry GT, Freeze HH, Morava E. Is X-linked, infantile onset ALG13-related developmental and epileptic encephalopathy a congenital disorder of glycosylation?. Epilepsia. 2021 Feb;62(2):335-336. doi: 10.1111/epi.16817. Epub 2021 Feb 11.

Starosta RT, Boyer S, Tahata S, Raymond K, Lee HE, Wolfe LA, Lam C, Edmondson AC, Schwartz IVD, Morava E. Liver manifestations in a cohort of 39 patients with congenital disorders of glycosylation: pin-pointing the characteristics of liver injury and proposing recommendations for follow-up. Orphanet J Rare Dis. 2021 Jan 7;16(1):20. doi: 10.1186/s13023-020-01630-2.

Radenkovic S, Fitzpatrick-Schmidt T, Byeon SK, Madugundu AK, Saraswat M, Lichty A, Wong SYW, McGee S, Kubiak K, Ligezka A, Ranatunga W, Zhang Y, Wood T, Friez MJ, Clarkson K, Pandey A, Jones JR, Morava E. Expanding the clinical and metabolic phenotype of DPM2 deficient congenital disorders of glycosylation. Mol Genet Metab. 2021 Jan;132(1):27-37. doi: 10.1016/j.ymgme.2020.10.007. Epub 2020 Oct 17.

Poskanzer SA, Schultz MJ, Turgeon CT, Vidal-Folch N, Liedtke K, Oglesbee D, Gavrilov DK, Tortorelli S, Matern D, Rinaldo P, Bennett JT, Thies JM, Chang IJ, Beck AE, Raymond K, Allenspach EJ, Lam C. Immune dysfunction in MGAT2-CDG: A clinical report and review of the literature. Am J Med Genet A. 2021 Jan;185(1):213-218. doi: 10.1002/ajmg.a.61914. Epub 2020 Oct 12.

Altassan R, Radenkovic S, Edmondson AC, Barone R, Brasil S, Cechova A, Coman D, Donoghue S, Falkenstein K, Ferreira V, Ferreira C, Fiumara A, Francisco R, Freeze H, Grunewald S, Honzik T, Jaeken J, Krasnewich D, Lam C, Lee J, Lefeber D, Marques-da-Silva D, Pascoal C, Quelhas D, Raymond KM, Rymen D, Seroczynska M, Serrano M, Sykut-Cegielska J, Thiel C, Tort F, Vals MA, Videira P, Voermans N, Witters P, Morava E. International consensus guidelines for phosphoglucomutase 1 deficiency (PGM1-CDG): Diagnosis, follow-up, and management. J Inherit Metab Dis. 2021 Jan;44(1):148-163. doi: 10.1002/jimd.12286. Epub 2020 Sep 15.

Wilson MP, Garanto A, Pinto E Vairo F, Ng BG, Ranatunga WK, Ventouratou M, Baerenfaenger M, Huijben K, Thiel C, Ashikov A, Keldermans L, Souche E, Vuillaumier-Barrot S, Dupré T, Michelakakis H, Fiumara A, Pitt J, White SM, Lim SC, Gallacher L, Peters H, Rymen D, Witters P, Ribes A, Morales-Romero B, Rodríguez-Palmero A, Ballhausen D, de Lonlay P, Barone R, Janssen MCH, Jaeken J, Freeze HH, Matthijs G, Morava E, Lefeber DJ. Active site variants in STT3A cause a dominant type I congenital disorder of glycosylation with neuromusculoskeletal findings. Am J Hum Genet. 2021 Nov 4;108(11):2130-2144. doi: 10.1016/j.ajhg.2021.09.012. Epub 2021 Oct 14. PMID: 34653363; PMCID: PMC8595932.

Congenital disorders of glycosylation (CDGs) are a group of rare diseases characterized by hypoglycosylation. The STT3A gene plays an essential role in protein N-glycosylation. In this study, researchers identified 16 individuals from nine families who have variants in STT3A, leading to an autosomal-dominant CDG. They describe the features of these individuals including variable skeletal anomalies, short stature, large head, muscle cramps, and in some, intellectual disability. The authors also present data to support a dominant form of STT3A-CDG that is unusual among type I CDGs.

Ferrer A, Starosta RT, Ranatunga W, Ungar D, Kozicz T, Klee E, Rust LM, Wick M, Morava E. Fetal glycosylation defect due to ALG3 and COG5 variants detected via amniocentesis: Complex glycosylation defect with embryonic lethal phenotype. Mol Genet Metab. 2020 Dec;131(4):424-429. doi: 10.1016/j.ymgme.2020.11.003. Epub 2020 Nov 7.

Ng BG, Eklund EA, Shiryaev SA, Dong YY, Abbott MA, Asteggiano C, Bamshad MJ, Barr E, Bernstein JA, Chelakkadan S, Christodoulou J, Chung WK, Ciliberto MA, Cousin J, Gardiner F, Ghosh S, Graf WD, Grunewald S, Hammond K, Hauser NS, Hoganson GE, Houck KM, Kohler JN, Morava E, Larson AA, Liu P, Madathil S, McCormack C, Meeks NJL, Miller R, Monaghan KG, Nickerson DA, Palculict TB, Papazoglu GM, Pletcher BA, Scheffer IE, Schenone AB, Schnur RE, Si Y, Rowe LJ, Serrano Russi AH, Russo RS, Thabet F, Tuite A, Villanueva MM, Wang RY, Webster RI, Wilson D, Zalan A; Undiagnosed Diseases Network, University of Washington Center for Mendelian Genomics (UW-CMG), Wolfe LA, Rosenfeld JA, Rhodes L, Freeze HH. Predominant and novel de novo variants in 29 individuals with ALG13 deficiency: Clinical description, biomarker status, biochemical analysis, and treatment suggestions. J Inherit Metab Dis. 2020 Nov;43(6):1333-1348. doi: 10.1002/jimd.12290. Epub 2020 Aug 5.

Del Caño-Ochoa F, Ng BG, Abedalthagafi M, Almannai M, Cohn RD, Costain G, Elpeleg O, Houlden H, Karimiani EG, Liu P, Manzini MC, Maroofian R, Muriello M, Al-Otaibi A, Patel H, Shimon E, Sutton VR, Toosi MB, Wolfe LA, Rosenfeld JA, Freeze HH, Ramón-Maiques S. Cell-based analysis of CAD variants identifies individuals likely to benefit from uridine therapy. Genet Med. 2020 Oct;22(10):1598-1605. doi: 10.1038/s41436-020-0833-2. Epub 2020 May 28.

Qian Z, Van den Eynde J, Heymans S, Mertens L, Morava E. Vascular ring anomaly in a patient with phosphomannomutase 2 deficiency: A case report and review of the literature. JIMD Rep. 2020 Aug 19;56(1):27-33. doi: 10.1002/jmd2.12160. eCollection 2020 Nov.

Čechová A, Altassan R, Borgel D, Bruneel A, Correia J, Girard M, Harroche A, Kiec-Wilk B, Mohnike K, Pascreau T, Pawliński Ł, Radenkovic S, Vuillaumier-Barrot S, Aldamiz-Echevarria L, Couce ML, Martins EG, Quelhas D, Morava E, de Lonlay P, Witters P, Honzík T. Consensus guideline for the diagnosis and management of mannose phosphate isomerase-congenital disorder of glycosylation. J Inherit Metab Dis. 2020 Jul;43(4):671-693. doi: 10.1002/jimd.12241. Epub 2020 Apr 21.

Witters P, Tahata S, Barone R, Õunap K, Salvarinova R, Grønborg S, Hoganson G, Scaglia F, Lewis AM, Mori M, Sykut-Cegielska J, Edmondson A, He M, Morava E. Clinical and biochemical improvement with galactose supplementation in SLC35A2-CDG. Genet Med. 2020 Jun;22(6):1102-1107. doi: 10.1038/s41436-020-0767-8. Epub 2020 Feb 27.

Vaes L, Tiller GE, Pérez B, Boyer SW, Berry SA, Sarafoglou K, Morava E. PMM2-CDG caused by uniparental disomy: Case report and literature review. JIMD Rep. 2020 Apr 28;54(1):16-21. doi: 10.1002/jmd2.12122. eCollection 2020 Jul.

Zilmer M, Edmondson AC, Khetarpal SA, Alesi V, Zaki MS, Rostasy K, Madsen CG, Lepri FR, Sinibaldi L, Cusmai R, Novelli A, Issa MY, Fenger CD, Abou Jamra R, Reutter H, Briuglia S, Agolini E, Hansen L, Petäjä-Repo UE, Hintze J, Raymond KM, Liedtke K, Stanley V, Musaev D, Gleeson JG, Vitali C, O'Brien WT, Gardella E, Rubboli G, Rader DJ, Schjoldager KT, Møller RS. Novel congenital disorder of O-linked glycosylation caused by GALNT2 loss of function. Brain. 2020 Apr 1;143(4):1114-1126. doi: 10.1093/brain/awaa063.

Verheijen J, Wong SY, Rowe JH, Raymond K, Stoddard J, Delmonte OM, Bosticardo M, Dobbs K, Niemela J, Calzoni E, Pai SY, Choi U, Yamazaki Y, Comeau AM, Janssen E, Henderson L, Hazen M, Berry G, Rosenzweig SD, Aldhekri HH, He M, Notarangelo LD, Morava E. Defining a new immune deficiency syndrome: MAN2B2-CDG. J Allergy Clin Immunol. 2020 Mar;145(3):1008-1011. doi: 10.1016/j.jaci.2019.11.016. Epub 2019 Nov 24.

Verheijen J, Tahata S, Kozicz T, Witters P, Morava E. Therapeutic approaches in Congenital Disorders of Glycosylation (CDG) involving N-linked glycosylation: an update. Genet Med. 2020 Feb;22(2):268–279. doi: 10.1038/s41436-019-0647-2. Epub 2019 Sep 19. PMID: 31534212.

Moravej H, Altassan R, Jaeken J, Enns GM, Ellaway C, Balasubramaniam S, De Lonlay P, Coman D, Mercimek-Andrews S, Witters P, Morava E. Hypoglycemia in CDG patients due to PMM2 mutations: Follow up on hyperinsulinemic patients. JIMD Rep. 2019 Nov 25;51(1):76-81. doi: 10.1002/jmd2.12085. eCollection 2020 Jan.

Iyer S, Sam FS, DiPrimio N, Preston G, Verheijen J, Murthy K, Parton Z, Tsang H, Lao J, Morava E, Perlstein EO. Repurposing the aldose reductase inhibitor and diabetic neuropathy drug epalrestat for the congenital disorder of glycosylation PMM2-CDG. Dis Model Mech. 2019 Nov 11;12(11):dmm040584. doi: 10.1242/dmm.040584.