nach oben

Erschienen in:

20.01.2017 | Review

Liver involvement in congenital disorders of glycosylation (CDG). A systematic review of the literature

verfasst von: D. Marques-da-Silva, V. dos Reis Ferreira, M. Monticelli, P. Janeiro, P. A. Videira, P. Witters, J. Jaeken, D. Cassiman

Erschienen in: Journal of Inherited Metabolic Disease | Ausgabe 2/2017

Einloggen, um Zugang zu erhalten

Abstract

Congenital disorders of glycosylation (CDG) are a rapidly growing family of genetic diseases caused by defects in glycosylation. Nearly 100 CDG types are known so far. Patients present a great phenotypic diversity ranging from poly- to mono-organ/system involvement and from very mild to extremely severe presentation. In this literature review, we summarize the liver involvement reported in CDG patients. Although liver involvement is present in only a minority of the reported CDG types (22 %), it can be debilitating or even life-threatening. Sixteen of the patients we collated here developed cirrhosis, 10 had liver failure. We distinguish two main groups: on the one hand, the CDG types with predominant or isolated liver involvement including MPI-CDG, TMEM199-CDG, CCDC115-CDG, and ATP6AP1-CDG, and on the other hand, the CDG types associated with liver disease but not as a striking, unique or predominant feature, including PMM2-CDG, ALG1-CDG, ALG3-CDG, ALG6-CDG, ALG8-CDG, ALG9-CDG, PGM1-CDG, and COG-CDG. This review aims to facilitate CDG patient identification and to understand CDG liver involvement, hopefully leading to earlier diagnosis, and better management and treatment.

Nur mit Berechtigung zugänglich

AlSubhi S, AlHashem A, AlAzami A et al (2015) Further delineation of the ALG9-CDG phenotype. JIMD Rep 27:107–112CrossRefPubMedPubMedCentral

Arnoux JB, Boddaert N, Valayannopoulos V et al (2008) Risk assessment of acute vascular events in congenital disorder of glycosylation type Ia. Mol Genet Metab 93:444–449CrossRefPubMed

Aronica E, van Kempen AAMW, van der Heide M et al (2005) Congenital disorder of glycosylation type Ia: a clinicopathological report of a newborn infant with cerebellar pathology. Acta Neuropathol 109:433–442CrossRefPubMed

Babovic-Vuksanovic D, Patterson MC, Schwenk WF et al (1999) Severe hypoglycemia as a presenting symptom of carbohydrate-deficient glycoprotein syndrome. J Pediatr 135:775–781CrossRefPubMed

Barone R, Sturiale L, Fiumara A, Uziel G, Garozzo D, Jaeken J (2007) Borderline mental development in a congenital disorder of glycosylation (CDG) type Ia patient with multisystemic involvement (intermediate phenotype). J Inherit Metab Dis 30:107CrossRefPubMed

Blomme B, Van Steenkiste C, Callewaert N, Van Vlierberghe H (2009) Alteration of protein glycosylation in liver diseases. J Hepatol 50:592–603CrossRefPubMed

Chantret I, Dancourt J, Dupre T et al (2003) A deficiency in dolichyl-P-glucose: Glc1Man9GlcNAc2-PP-dolichyl alpha3-glucosyltransferase defines a new subtype of congenital disorders of glycosylation. J Biol Chem 298:9962–9971CrossRef

Choi R, Woo HI, Choe B-H (2015) Application of whole exome sequencing to a rare inherited metabolic disease with neurological and gastrointestinal manifestations: a congenital disorder of glycosylation mimicking glycogen storage disease. Clin Chim Acta 444:50–53CrossRefPubMed

Damen G, de Klerk H, Huijmans J, den Hollander J, Sinaasappel M (2004) Gastrointestinal and other clinical manifestations in 17 children with congenital disorders of glycosylation type Ia, Ib, and Ic. J Pediatr Gastroenterol Nutr 38:282–287CrossRefPubMed

de Koning TJ, Dorland L, van Diggelen OP et al (1998) A novel disorder of N-glycosylation due to phosphomannose isomerase deficiency. Biochem Biophys Res Commun 245:38–42CrossRefPubMed

de Lonlay P, Seta N (2009) The clinical spectrum of phosphomannose isomerase deficiency, with an evaluation of mannose treatment for CDG-Ib. Biochim Biophys Acta 1792:841–843CrossRefPubMed

de Lonlay P, Seta N, Barrot S et al (2001) A broad spectrum of clinical presentations in congenital disorders of glycosylation I: a series of 26 cases. J Med Genet 38:14–19CrossRefPubMedPubMedCentral

Eklund EA, Sun L, Westphal V, Northrop JL, Freeze HH, Scaglia F (2005) Congenital disorder of glycosylation (CDG)-Ih patient with a severe hepato-intestinal phenotype and evolving central nervous system pathology. J Pediatr 147:847–850CrossRefPubMed

Eklund EA, Sun L, Yang SP, Pasion RM, Thorland EC, Freeze HH (2006) Congenital disorder of glycosylation Ic due to a de novo deletion and an hALG-6 mutation. Biochem Biophys Res Commun 339:755–760CrossRefPubMed

Ferro JM, Viana P, Santos P (2016) Management of neurologic manifestations in patients with liver disease. Curr Treat Options Neurol 18:37CrossRefPubMed

Foulquier F, Vasile E, Schollen E et al (2006) Conserved oligomeric Golgi complex subunit 1 deficiency reveals a previously uncharacterized congenital disorder of glycosylation type II. PNAS 103:3764–3769CrossRefPubMedPubMedCentral

Frank CG, Grubenmann CE, Eyaid W, Berger EG, Aebi M, Hennet T (2004) Identification and functional analysis of a defect in the human ALG9 Gene: definition of congenital disorder of glycosylation type IL. Am J Hum Genet 75:146–150CrossRefPubMedPubMedCentral

Freeze HH, Chong JX, Bamshad MJ, Ng BG (2014) Solving glycosylation disorders: fundamental approaches reveal complicated pathways. Am J Hum Genet 94:161–175CrossRefPubMedPubMedCentral

Fung CW, Matthijs G, Sturiale L et al (2012) COG5-CDG with a mild neurohepatic presentation. JIMD Rep 3:67–70CrossRefPubMed

Grubenmann CE, Frank CG, Hülsmeier AJ et al (2004) Deficiency of the first mannosylation step in the N-glycosylation pathway causes congenital disorder of glycosylation type Ik. Hum Mol Genet 13:535–542CrossRefPubMed

Grünewald S (2009) The clinical spectrum of phosphomannomutase 2 deficiency (CDG-Ia). Biochim Biophys Acta 1792:827–834CrossRefPubMed

Grünewald S, De Vos R, Jaeken J (2003) Abnormal lysosomal inclusions in liver hepatocytes but not in fibroblasts in congenital disorders of glycosylation (CDG). J Inherit Metab Dis 26:49–54CrossRefPubMed

Hendriksz CJ, McClean P, Henderson MJ et al (2001) Successful treatment of carbohydrate deficient glycoprotein syndrome type 1b with oral mannose. Arch Dis Child 85:339–340CrossRefPubMedPubMedCentral

Hernández EM, Vega Pajares AIV, González BP et al (2008) Defecto congénito de glucosilación tipo Ib. experiencia en el tratamiento con manosa. An Pediatr (Barc) 69:358–365CrossRef

Höck M, Wegleiter K, Ralser E et al (2015) ALG8-CDG: novel patients and review of the literature. Orphanet J Rare Dis 10:73–80CrossRefPubMedPubMedCentral

Jaeken J, Morava E (2016) Congenital disorders of glycosylation and dolichol and glycosylphosphatidylinositol metabolism. In: Saudubray, Baumgartner, Walter (ed) Inborn metabolic diseases. diagnosis and treatment, 6th edn. Springer, Berlin, pp 607–622CrossRef

Jaeken J, Stibler H, Hagberg B (1991) The carbohydrate-deficient glycoprotein syndrome. a new inherited multisystemic disease with severe nervous system involvement. Acta Paediatr Scand Suppl 375:1–71PubMed

Jaeken J, Matthijs G, Saudubray J-M et al (1998) Phosphomannose isomerase deficiency: a carbohydrate-deficient glycoprotein syndrome with hepatic-intestinal presentation. Am J Hum Genet 62:1535–1539CrossRefPubMedPubMedCentral

Jaeken J, Lefeber D, Matthijs G (2014) Clinical utility gene card for: phosphomannose isomerase deficiency. Eur J Hum Genet. doi:10.1038/ejhg.2014.29

Jaeken J, Lefeber D, Matthijs G (2015a) Clinical utility gene card for: ALG1 defective congenital disorder of glycosylation. Eur J Hum Genet. doi:10.1038/ejhg.2015.9

Jaeken J, Lefeber D, Matthijs G (2015b) Clinical utility gene card for: ALG6 defective congenital disorder of glycosylation. Eur J Hum Genet. doi:10.1038/ejhg.2014.146

Jansen JC, Timal S, van Scherpenzeel M et al (2016a) TMEM199 deficiency is a disorder of Golgi homeostasis characterized by elevated aminotransferases, alkaline phosphatase, and cholesterol and abnormal glycosylation. Am J Hum Genet 98:322–330CrossRefPubMedPubMedCentral

Jansen JC, Cirak S, van Scherpenzeel M et al (2016b) CCDC115 deficiency causes a disorder of golgi homeostasis with abnormal protein glycosylation. Am J Hum Genet 98:310–321CrossRefPubMedPubMedCentral

Jansen EJR, Timal S, Ryan M et al (2016c) ATP6AP1 deficiency causes an immunodeficiency with hepatopathy, cognitive impairment and abnormal protein glycosylation. Nat Commun 7:11600CrossRefPubMedPubMedCentral

Janssen MCH, de Kleine RH, van den Berg AP et al (2014) Successful liver transplantation and long-term follow-up in a patient with MPI-CDG. Pediatrics 134:e279–e283CrossRefPubMed

Kelly DF, Boneh A, Pitsch S et al (2001) Carbohydrate-deficient glycoprotein syndrome 1b: a new answer to an old diagnostic dilemma. J Paediatr Child Health 37:510–512CrossRefPubMed

Kjaergaard S, Schwartz M, Skovby F (2001) Congenital disorder of glycosylation type Ia (CDG-Ia): phenotypic spectrum of the R141H/F119L genotype. Arch Dis Child 85:236–239CrossRefPubMedPubMedCentral

Kodera H, Ando N, Yuasa I et al (2015) Mutations in COG2 encoding a subunit of the conserved oligomeric golgi complex cause a congenital disorder of glycosylation. Clin Genet 87:455–460CrossRefPubMed

Kornak U, Reynders E, Dimopoulou A et al (2008) Impaired glycosylation and cutis laxa caused by mutations in the vesicular H+-ATPase subunit ATP6V0A2. Nat Genet 40:32–34CrossRefPubMed

Lepais L, Cheillan D, Frachon SC et al (2015) ALG3-CDG: report of two siblings with antenatal features carrying homozygous p.Gly96Arg Mutation. Am J Med Genet 167A:2748–2754CrossRefPubMed

Liem YS, Bode L, Freeze HH, Leebeek FWG, Zandbergen AAM, Wilson JHP (2008) Using heparin therapy to reverse protein-losing enteropathy in a patient with CDG-Ib. Nat Clin Pract Gastroenterol Hepatol 5:220–224CrossRefPubMed

Mention K, Lacaille F, Valayannopoulos V et al (2008) Development of liver disease despite mannose treatment in two patients with CDG-Ib. Mol Genet Metabol 93:40–43CrossRef

Miura Y, Tay SKH, Aw MM, Eklund E, Freeze HH (2005) Clinical and biochemical characterization of a patient with congenital disorder of glycosylation (CDG) IIX. J Pediatr 147:851–853CrossRefPubMed

Monin ML, Mignot C, De Lonlay P et al (2014) 29 French adult patients with PMM2-congenital disorder of glycosylation: outcome of the classical pediatric phenotype and depiction of a late-onset phenotype. Orphanet J Rare Dis 9:207CrossRefPubMedPubMedCentral

Monticelli M, Ferro T, Jaeken J, Dos Reis Ferreira V, Videira PA (2016) Immunological aspects of congenital disorders of glycosylation (CDG): a review. J Inherit Metab Dis 39:765–780CrossRefPubMed

Morava E (2014) Galactose supplementation in phosphoglucomutase-1 deficiency; review and outlook for a novel treatable CDG. Mol Genet Metab 112:275–279CrossRefPubMedPubMedCentral

Morava E, Zeevaert R, Korsch E et al (2007) A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia. Eur J Hum Genet 15:638–665CrossRefPubMed

Morava E, Vodopiutz J, Lefeber DJ et al (2012) Defining the phenotype in congenital disorder of glycosylation due to ALG1 mutations. Pediatrics 130:e1034–e1039CrossRefPubMed

Morava E, Tiemes V, Thiel C et al (2016) ALG6-CDG: a recognizable phenotype with epilepsy, proximal muscle weakness, ataxia and behavior and limb anomalies. J Inherit Metab Dis 39:713–723CrossRefPubMed

Ng BG, Kranz C, Hagebeuk EEO et al (2007) Molecular and clinical characterization of a Moroccan Cog7 deficient patient. Mol Genet Metab 91:201–204CrossRefPubMedPubMedCentral

Ng BG, Sharma V, Sun L et al (2011) Identification of the first COG-CDG patient of Indian origin. Mol Genet Metab 102:364–367CrossRefPubMed

Ng BG, Shiryaev SA, Rymen D et al (2016) ALG1-CDG: clinical and molecular characterization of 39 unreported patients. Hum Mutat 37:653–660CrossRefPubMedPubMedCentral

Niehues R, Hasilik M, Alton G et al (1998) Carbohydrate-deficient glycoprotein syndrome type Ib. phosphomannose isomerase deficiency and mannose therapy. J Clin Invest 101:1414–1420CrossRefPubMedPubMedCentral

Ono H, Sakura N, Yamashita K, Yuasa I, Ohno K (2003) Novel nonsense mutation (R194X) in the PMM2 gene in a Japanese patient with congenital disorder of glycosylation type Ia. Brain Dev 27:525–528CrossRef

Panneerselvam K, Freeze HH (1996) Mannose enters mammalian cells using a specific transporter that is insensitive to glucose. J Biol Chem 271:9417–9421CrossRefPubMed

Reynders E, Foulquier F, Leão Teles E et al (2009) Golgi function and dysfunction in the first COG4-deficient CDG type II patient. Hum Mol Genet 18:3244–3256CrossRefPubMedPubMedCentral

Rohlfing A-K, Rust S, Reunert J et al (2014) ALG1-CDG: a new case with early fatal outcome. Gene 534:345–351CrossRefPubMed

Rymen D, Winter J, Van Hasselt PM et al (2015) Key features and clinical variability of COG6-CDG. Mol Genet Metabol 116:163–170CrossRef

Schollen E, Frank CG, Keldermans L et al (2004) Clinical and molecular features of three patients with congenital disorders of glycosylation type Ih (CDG-Ih) (ALG8 deficiency). J Med Genet 41:550–556CrossRefPubMedPubMedCentral

Serrano M, de Diego V, Muchart J et al (2015) Phosphomannomutase deficiency (PMM2-CDG): ataxia and cerebellar assessment. Orphanet J Rare Dis 10:138CrossRefPubMedPubMedCentral

Shanti B, Silink M, Bhattacharya K et al (2009) Congenital disorder of glycosylation type Ia: heterogeneity in the clinical presentation from multivisceral failure to hyperinsulinaemic hypoglycaemia as leading symptoms in three infants with phosphomannomutase deficiency. J Inherit Metab Dis 32:S241–S251CrossRefPubMed

Sorte H, Mørkrid L, Rødningen O et al (2012) Severe ALG8-CDG (CDG-Ih) associated with homozygosity for two novel missense mutations detected by exome sequencing of candidate genes. Eur J Med Genet 55:196–202CrossRefPubMed

Spaapen LJM, Bakker JA, Van Der Meer SB et al (2005) Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder. J Inherit Metab Dis 28:707–714CrossRefPubMed

Sparks SE, Krasnewich DM (2014) Congenital disorders of N-linked glycosylation. pathway overview. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Fong CT, Mefford HC, Smith RJH, Stephens K (eds) eneReviews®. University of Washington, Seattle, pp 1993–2016

Sun L, Eklund EA, Chung WK, Wang C, Cohen J, Freeze HH (2005) Congenital disorder of glycosylation Id presenting with hyperinsulinemic hypoglycemia and islet cell hyperplasia. J Clin Endocrinol Metab 90:4371–4375CrossRefPubMed

Tegtmeyer LC, Rust S, van Scherpenzeel M et al (2014) Multiple phenotypes in phosphoglucomutase 1 deficiency. N Eng J Med 370:533–542CrossRef

Vesela K, Honzik T, Hansikova H et al (2009) A new case of ALG8 deficiency (CDG Ih). J Inherit Metab Dis 32:259–264CrossRef

Vleugels W, Keldermans L, Jaeken J et al (2009) Quality control of glycoproteins bearing truncated glycans in an ALG9-defective (CDG-IL) patient. Glycobiology 19:910–917CrossRefPubMed

Weinstein M, Schollen, Matthijs G et al (2005) CDG-IL: an infant with a novel mutation in the ALG9 gene and additional phenotypic features. Am J Med Genet 136A:194–197CrossRef

Westphal V, Kjaergaard S, Davis JÁ, Peterson SM, Skovby F, Freeze HH (2001) Genetic and metabolic analysis of the first adult with congenital disorder of glycosylation type Ib: long-term outcome and effects of mannose supplementation. Mol Genet Metabol 73:77–85CrossRef

Wong SY, Beamer LJ, Gadomski T et al (2016) Defining the phenotype and assessing severity in phosphoglucomutase-1 deficiency. J Pediatr 175:130–136CrossRefPubMed

Wu X, Steet RA, Bohorov O et al (2004) Mutation of the COG complex subunit gene COG7 causes a lethal congenital disorder. Nat Med 10:518–523CrossRefPubMed

Zeevaert R, Foulquier F, Cheillan D et al (2009) A new mutation in COG7 extends the spectrum of COG subunit deficiencies. Eur J Med Genet 52:303–305CrossRefPubMed

Titel: Liver involvement in congenital disorders of glycosylation (CDG). A systematic review of the literature
verfasst von: D. Marques-da-Silva
V. dos Reis Ferreira
M. Monticelli
P. Janeiro
P. A. Videira
P. Witters
J. Jaeken
D. Cassiman
Publikationsdatum: 20.01.2017
Verlag: Springer Netherlands
Erschienen in: Journal of Inherited Metabolic Disease / Ausgabe 2/2017
Print ISSN: 0141-8955
Elektronische ISSN: 1573-2665
DOI: https://doi.org/10.1007/s10545-016-0012-4

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

19.04.2024 | Vorhofflimmern | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Liver involvement in congenital disorders of glycosylation (CDG). A systematic review of the literature

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Parodontalbehandlung verbessert Prognose bei Katheterablation

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Denken Sie bei starker Blutung auch an die Hemmkörper-Hämophilie

Update Innere Medizin

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2017

International clinical guideline for the management of classical galactosemia: diagnosis, treatment, and follow-up

A SLC39A8 variant causes manganese deficiency, and glycosylation and mitochondrial disorders

Is 2D speckle tracking echocardiography useful for detecting and monitoring myocardial dysfunction in adult m.3243A>G carriers? — a retrospective pilot study

Mortality after hematopoietic stem cell transplantation for severe mucopolysaccharidosis type I: the 30-year University of Minnesota experience

Nenad Blau (ed.). Phenylketonuria and BH4 deficiencies

News and views

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Parodontalbehandlung verbessert Prognose bei Katheterablation

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Denken Sie bei starker Blutung auch an die Hemmkörper-Hämophilie

Update Innere Medizin