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Congenital disorder of deglycosylation(CDDG)

MedGen UID:
815321
•Concept ID:
C3808991
•
Disease or Syndrome
Synonym: CDDG
SNOMED CT: NGLY1-congenital disorder of deglycosylation (768846004); Alacrimia, choreoathetosis, liver dysfunction syndrome (768846004); Deficiency of N-glycanase 1 (768846004); N-glycanase 1 congenital disorder of deglycosylation (768846004)
 
Related genes: NGLY1, MAN2C1
 
Monarch Initiative: MONDO:0031376
OMIM®: 610661; 615273
OMIM® Phenotypic series: PS615273

Disease characteristics

Excerpted from the GeneReview: NGLY1-Related Congenital Disorder of Deglycosylation
Individuals with NGLY1-related congenital disorder of deglycosylation (NGLY1-CDDG) typically display a clinical tetrad of developmental delay / intellectual disability in the mild to profound range, hypo- or alacrima, elevated liver transaminases that may spontaneously resolve in childhood, and a complex hyperkinetic movement disorder that can include choreiform, athetoid, dystonic, myoclonic, action tremor, and dysmetric movements. About half of affected individuals will develop clinical seizures. Other findings may include obstructive and/or central sleep apnea, oral motor defects that affect feeding ability, auditory neuropathy, constipation, scoliosis, and peripheral neuropathy. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Genetically Related (Allelic) Disorders  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Christina Lam  |  Lynne Wolfe  |  Anna Need, et. al.   view full author information

Additional description

From MedlinePlus Genetics
NGLY1-congenital disorder of deglycosylation (NGLY1-CDDG) is an inherited condition that affects many parts of the body. The severity of the signs and symptoms varies widely among people with the condition.

Individuals with NGLY1-CDDG typically develop features of the condition during infancy. They often have delayed development of speech and motor skills, such as sitting and walking, and weak muscle tone (hypotonia). Many affected individuals have movement abnormalities, such as uncontrolled movements of the limbs (choreoathetosis), and some develop seizures that are difficult to treat. Individuals with NGLY1-CDDG may also have problems with liver function. Some affected individuals have eye abnormalities, including degeneration of the nerves that carry information from the eyes to the brain (optic atrophy) and changes in the light-sensing tissue at the back of the eye (the retina). A reduction or absence of tears (hypolacrima or alacrima) is a common feature of NGLY1-CDDG.  https://medlineplus.gov/genetics/condition/ngly1-congenital-disorder-of-deglycosylation

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Congenital disorder of deglycosylation in Orphanet.

Professional guidelines

PubMed

How do genetic tests answer questions about neurodevelopmental differences? A sociological take.
Navon D
Dev Med Child Neurol 2022 Dec;64(12):1462-1469. Epub 2022 Aug 13 doi: 10.1111/dmcn.15376. PMID: 35962997
Repurposing of Proton Pump Inhibitors as first identified small molecule inhibitors of endo-β-N-acetylglucosaminidase (ENGase) for the treatment of NGLY1 deficiency, a rare genetic disease.
Bi Y, Might M, Vankayalapati H, Kuberan B
Bioorg Med Chem Lett 2017 Jul 1;27(13):2962-2966. Epub 2017 May 5 doi: 10.1016/j.bmcl.2017.05.010. PMID: 28512024Free PMC Article

Recent clinical studies

Etiology

Progressive myoclonic epilepsy as an expanding phenotype of NGLY1-associated congenital deglycosylation disorder: A case report and review of the literature.
Sonoda Y, Fujita A, Torio M, Mukaino T, Sakata A, Matsukura M, Yonemoto K, Hatae K, Ichimiya Y, Chong PF, Ochiai M, Wada Y, Kadoya M, Okamoto N, Murakami Y, Suzuki T, Isobe N, Shigeto H, Matsumoto N, Sakai Y, Ohga S
Eur J Med Genet 2024 Feb;67:104895. Epub 2023 Dec 7 doi: 10.1016/j.ejmg.2023.104895. PMID: 38070824

Diagnosis

Development of new NGLY1 assay systems - toward developing an early screening method for NGLY1 deficiency.
Hirayama H, Fujihira H, Suzuki T
Glycobiology 2024 Sep 30;34(11) doi: 10.1093/glycob/cwae067. PMID: 39206713Free PMC Article
Analysis of urinary oligosaccharide excretion patterns by UHPLC/HRAM mass spectrometry for screening of lysosomal storage disorders.
Hagemeijer MC, van den Bosch JC, Bongaerts M, Jacobs EH, van den Hout JMP, Oussoren E, Ruijter GJG
J Inherit Metab Dis 2023 Mar;46(2):206-219. Epub 2023 Feb 28 doi: 10.1002/jimd.12597. PMID: 36752951
Liver involvement in NGLY1 congenital disorder of deglycosylation.
Lipiński P, Cielecka-Kuszyk J, Socha P, Tylki-Szymańska A
Pol J Pathol 2020;71(1):66-68. doi: 10.5114/pjp.2020.92994. PMID: 32429657
Aspartylglycosamine is a biomarker for NGLY1-CDDG, a congenital disorder of deglycosylation.
Haijes HA, de Sain-van der Velden MGM, Prinsen HCMT, Willems AP, van der Ham M, Gerrits J, Couse MH, Friedman JM, van Karnebeek CDM, Selby KA, van Hasselt PM, Verhoeven-Duif NM, Jans JJM
Mol Genet Metab 2019 Aug;127(4):368-372. Epub 2019 Jul 9 doi: 10.1016/j.ymgme.2019.07.001. PMID: 31311714

Prognosis

Progressive myoclonic epilepsy as an expanding phenotype of NGLY1-associated congenital deglycosylation disorder: A case report and review of the literature.
Sonoda Y, Fujita A, Torio M, Mukaino T, Sakata A, Matsukura M, Yonemoto K, Hatae K, Ichimiya Y, Chong PF, Ochiai M, Wada Y, Kadoya M, Okamoto N, Murakami Y, Suzuki T, Isobe N, Shigeto H, Matsumoto N, Sakai Y, Ohga S
Eur J Med Genet 2024 Feb;67:104895. Epub 2023 Dec 7 doi: 10.1016/j.ejmg.2023.104895. PMID: 38070824
NGLY1 deficiency: estimated incidence, clinical features, and genotypic spectrum from the NGLY1 Registry.
Stanclift CR, Dwight SS, Lee K, Eijkenboom QL, Wilsey M, Wilsey K, Kobayashi ES, Tong S, Bainbridge MN
Orphanet J Rare Dis 2022 Dec 17;17(1):440. doi: 10.1186/s13023-022-02592-3. PMID: 36528660Free PMC Article
Expanding DSD Phenotypes Associated with Variants in the DEAH-Box RNA Helicase DHX37.
Zidoune H, Martinerie L, Tan DS, Askari M, Rezgoune D, Ladjouze A, Boukri A, Benelmadani Y, Sifi K, Abadi N, Satta D, Rastari M, Seresht-Ahmadi M, Bignon-Topalovic J, Mazen I, Leger J, Simon D, Brauner R, Totonchi M, Jauch R, Bashamboo A, McElreavey K
Sex Dev 2021;15(4):244-252. Epub 2021 Jul 22 doi: 10.1159/000515924. PMID: 34293745
Acute liver failure in a male patient with NGLY1-congenital disorder of deglycosylation.
Rios-Flores IM, Bonal-Pérez MÁ, Castellanos-González A, Velez-Gómez E, Bertoli-Avella AM, Bobadilla-Morales L, Peña-Padilla C, Appendini-Andrade V, Corona-Rivera A, Romero-Valenzuela I, Corona-Rivera JR
Eur J Med Genet 2020 Aug;63(8):103952. Epub 2020 May 15 doi: 10.1016/j.ejmg.2020.103952. PMID: 32422350
Prospective phenotyping of NGLY1-CDDG, the first congenital disorder of deglycosylation.
Lam C, Ferreira C, Krasnewich D, Toro C, Latham L, Zein WM, Lehky T, Brewer C, Baker EH, Thurm A, Farmer CA, Rosenzweig SD, Lyons JJ, Schreiber JM, Gropman A, Lingala S, Ghany MG, Solomon B, Macnamara E, Davids M, Stratakis CA, Kimonis V, Gahl WA, Wolfe L
Genet Med 2017 Feb;19(2):160-168. Epub 2016 Jul 7 doi: 10.1038/gim.2016.75. PMID: 27388694Free PMC Article

Clinical prediction guides

Progressive myoclonic epilepsy as an expanding phenotype of NGLY1-associated congenital deglycosylation disorder: A case report and review of the literature.
Sonoda Y, Fujita A, Torio M, Mukaino T, Sakata A, Matsukura M, Yonemoto K, Hatae K, Ichimiya Y, Chong PF, Ochiai M, Wada Y, Kadoya M, Okamoto N, Murakami Y, Suzuki T, Isobe N, Shigeto H, Matsumoto N, Sakai Y, Ohga S
Eur J Med Genet 2024 Feb;67:104895. Epub 2023 Dec 7 doi: 10.1016/j.ejmg.2023.104895. PMID: 38070824
Analysis of urinary oligosaccharide excretion patterns by UHPLC/HRAM mass spectrometry for screening of lysosomal storage disorders.
Hagemeijer MC, van den Bosch JC, Bongaerts M, Jacobs EH, van den Hout JMP, Oussoren E, Ruijter GJG
J Inherit Metab Dis 2023 Mar;46(2):206-219. Epub 2023 Feb 28 doi: 10.1002/jimd.12597. PMID: 36752951
N-glycoproteomics reveals distinct glycosylation alterations in NGLY1-deficient patient-derived dermal fibroblasts.
Budhraja R, Saraswat M, De Graef D, Ranatunga W, Ramarajan MG, Mousa J, Kozicz T, Pandey A, Morava E
J Inherit Metab Dis 2023 Jan;46(1):76-91. Epub 2022 Oct 4 doi: 10.1002/jimd.12557. PMID: 36102038Free PMC Article
Aspartylglycosamine is a biomarker for NGLY1-CDDG, a congenital disorder of deglycosylation.
Haijes HA, de Sain-van der Velden MGM, Prinsen HCMT, Willems AP, van der Ham M, Gerrits J, Couse MH, Friedman JM, van Karnebeek CDM, Selby KA, van Hasselt PM, Verhoeven-Duif NM, Jans JJM
Mol Genet Metab 2019 Aug;127(4):368-372. Epub 2019 Jul 9 doi: 10.1016/j.ymgme.2019.07.001. PMID: 31311714
Prospective phenotyping of NGLY1-CDDG, the first congenital disorder of deglycosylation.
Lam C, Ferreira C, Krasnewich D, Toro C, Latham L, Zein WM, Lehky T, Brewer C, Baker EH, Thurm A, Farmer CA, Rosenzweig SD, Lyons JJ, Schreiber JM, Gropman A, Lingala S, Ghany MG, Solomon B, Macnamara E, Davids M, Stratakis CA, Kimonis V, Gahl WA, Wolfe L
Genet Med 2017 Feb;19(2):160-168. Epub 2016 Jul 7 doi: 10.1038/gim.2016.75. PMID: 27388694Free PMC Article

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