Hostname: page-component-cd9895bd7-jkksz Total loading time: 0 Render date: 2024-12-27T15:28:37.588Z Has data issue: false hasContentIssue false
  • English
  • Français

Cardiomyopathy in congenital disorders of glycosylation

Published online by Cambridge University Press:  24 May 2005

Josef Gehrmann ,
Kristina Sohlbach ,
Michael Linnebank ,
Hans-Josef Böhles ,
Stephan Buderus ,
Hans Gerd Kehl ,
Johannes Vogt ,
Erik Harms  and
Thorsten Marquardt
Josef Gehrmann
Affiliation:
Department of Pediatric Cardiology, Westfalische Wilhelms-Universitat Munster/Westf., Munster, Germany
Kristina Sohlbach
Affiliation:
Department of Pediatrics, Westfalische Wilhelms-Universitat Munster/Westf., Munster, Germany
Michael Linnebank
Affiliation:
Department of Pediatrics, Westfalische Wilhelms-Universitat Munster/Westf., Munster, Germany
Hans-Josef Böhles
Affiliation:
Department of Pediatrics, Johann Wolfgang Goethe-Universitat, Frankfurt/Main, Bonn, Germany
Stephan Buderus
Affiliation:
Department of Pediatrics, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany
Hans Gerd Kehl
Affiliation:
Department of Pediatric Cardiology, Westfalische Wilhelms-Universitat Munster/Westf., Munster, Germany
Johannes Vogt
Affiliation:
Department of Pediatric Cardiology, Westfalische Wilhelms-Universitat Munster/Westf., Munster, Germany
Erik Harms
Affiliation:
Department of Pediatrics, Westfalische Wilhelms-Universitat Munster/Westf., Munster, Germany
Thorsten Marquardt
Affiliation:
Department of Pediatrics, Westfalische Wilhelms-Universitat Munster/Westf., Munster, Germany
Get access Rights & Permissions [Opens in a new window]

Abstract

Congenital disorders of glycosylation are a group of inherited metabolic multisystem disorders characterized by defects in the glycosylation of proteins and lipids. In most cases, neuromuscular disease is present. The purpose of this study was to characterize the cardiological aspects in this disorder.

From the literature, we identified six children with congenital disorders of glycosylation associated with cardiac disease. We then screened for cardiovascular manifestations 20 patients diagnosed with congenital disorders of glycosylation at our own institution.

Of the 6 patients identified in the literature, 4 had hypertrophic cardiomyopathy, while in the other 2 the cardiac diagnosis was unclear. The mean age at cardiac diagnosis was 5 months, with a range from 34 weeks to 24 months. Of the patients, five had died at a mean age of 3.5 months, with a range from 1.5 to 6 months, with one documented cardiac death. Three of our 20 patients (15%) had coexistent cardiomyopathy, and in three additional patients presenting with cardiomyopathy we made the diagnosis of a congenital disorder of glycosylation. In our cohort, dilated cardiomyopathy was found in two-thirds of the patients, with hypertrophic cardiomyopathy in the other third. The mean age at cardiac diagnosis was 19 months, with a range from 0.5 to 84 months. Of these patients, two died in infancy at a mean age of 4 months, specifically at 1.5 and 7 months, due to cardiac disease, with one dying suddenly. The remaining four patients are alive with minor to severe cardiac dysfunction.

We conclude that congenital disorders of glycosylation have to be considered in the differential diagnosis of children presenting with cardiomyopathy, and that all patients with congenital disorders of glycosylation should be screened for an associated cardiomyopathy. Cardiac involvement contributes significantly to morbidity and mortality, and probably to sudden cardiac death in this disorder.

Keywords

Hypertrophic cardiomyopathydilated cardiomyopathysudden cardiac death
Type
Original Article
Information
Cardiology in the Young , Volume 13 , Issue 4 , August 2003 , pp. 345 - 351
Copyright
© 2003 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Marquardt T, Freeze HH. Congenital disorders of glycosylation. Glycosylation defects in man and biological models for their study. Biol Chem 2001; 382: 161–177.Google Scholar
Marquardt T, Hülskamp G, Gehrmann J, Debus V, Harms E, Kehl HG. Severe transient myocardial ischaemia causes by hypertrophic cardiomyopathy in a patient with congenital disorder of glycosylation type Ia. Eur J Pediatr 2002; 161: 524–527.Google Scholar
Jaeken J, van Eijk HG, van der Heul C, Corbeel L, Eeckels R, Eggermont E. Sialic acid-deficient serum and cerebrospinal fluid transferrin in an newly recognized genetic syndrome. Clin Chim Acta 1984; 144: 245–247.Google Scholar
Jaeken J, Vanderschueren-Lodeweyckx M, Casaer P, et al. Familial psychomotor retardation with markedly fluctuating serum prolactin, FSH and GH levels, partial TBG deficiency, increased serum arylsulphatase A and increased CSF protein: a new syndrome? Pediatr Res 1980; 14: 179.Google Scholar
Clayton PT, Winchester BG, Keir G. Hypertrophic obstructive cardiomyopathy in a neonate with the carbohydrate-deficient glycoprotein syndrome. J Inher Metab Dis 1992; 15: 857–861.Google Scholar
Hagberg BA, Blennow G, Kristiansson B, Stibler H. Carbohydrate-deficient glycoprotein syndromes: peculiar group of new disorders. Pediatr Neurol 1993; 9: 255–262.Google Scholar
Harding BN, Dunger DB, Grant DB, Erdohazi M. Familial olivopontocerebellar atrophy with neonatal onset: a recessively inherited syndrome with systemic and biochemical abnormalities. J Neurol Neurosurg Psychiatry 1988; 51: 385–390.Google Scholar
Jaeken J, Hagberg B, Strømme P. Clinical presentation and natural course of the carbohydrate-deficient glycoprotein syndrome. Acta Paediatr Scand 1991; 375 (Suppl): 6–13.Google Scholar
Kristiansson B, Stibler H, Conradi N, Eriksson BO, Ryd W. The heart and pericardial effusions in CDGS-I (carbohydrate-deficient glycoprotein syndrome type I). J Inherit Metab Dis 1998; 21: 112–124.Google Scholar
Horslen SP, Clayton PT, Harding BN, Hall NA, Keir G, Winchester B. Olivopontocerebellar atrophy of neonatal onset and disialotransferrin developmental deficiency syndrome. Arch Dis Child 1991; 66: 1027–1032.Google Scholar
Hutchesson AC, Gray RG, Spencer DA, Keir G. Carbohydrate-deficient glycoprotein syndrome; multiple abnormalities and diagnostic delay. Arch Dis Child 1995; 72: 445–446.Google Scholar
Garcia Silva MT, de Castro J, Stibler H, et al. Prenatal hypertrophic cardiomyopathy and pericardial effusion in carbohydrate-deficient glycoprotein syndrome. J Inherit Metab Dis 1996; 19: 257–259.Google Scholar
Imtiaz F, Worthington V, Champion M, et al. Genotypes and phenotypes of patients in the UK with carbohydrate-deficient glycoprotein syndrome type 1. J Inherit Metab Dis 2000; 23: 162–174.Google Scholar
Charlwood J, Clayton P, Johnson A, Keir G, Mian N, Winchester B (1997). A case of carbohydrate-deficient glycoprotein syndrome type 1 (CDGS type 1) with normal phosphomannomutase deficiency. J Inherit Metab Dis 2000; 20: 817–827.Google Scholar
Clayton P, Winchester B, di Tomaso E, Young E, Keir G, Rodeck C. Carbohydrate-deficient glycoprotein syndrome: normal glycosylation in the fetus. Lancet 1993; 341: 956.Google Scholar
Di Rocco M, Barone R, Adami A, et al. Carbohydrate-deficient glycoprotein syndromes: the Italian experience. J Inherit Metab Dis 2000; 23: 391–395.Google Scholar
Freeze HH. Human glycosylation disorders and sugar supplement therapy. Biochem Biophys Res Comm 1999; 255: 189–193.Google Scholar
Niehues R, Hasilik M, Alton G, et al. Carbohydrate-deficient glycoprotein syndrome type Ib. Phosphomannose isomerase deficiency and mannose therapy. J Clin Invest 1998; 101: 1414–1420.Google Scholar
Lühn K, Marquardt T, Harms E, Vestweber D. Discontinuation of fucose therapy in LAD II causes rapid loss of selectin ligands and rise of leukocyte counts. Blood 2001; 97: 330–332.Google Scholar
Marquardt T, Lühn K, Srikrishna G, Freeze HH, Harms E, Vestweber D. Correction of leukocyte adhesion deficiency type II with oral fucose. Blood 1999; 94: 3976–3985.Google Scholar
Schwartz ML, Cox GF, Lin AE, et al. Clinical approach to genetic cardiomyopathy in children. Circulation 1996; 94: 2021–2038.Google Scholar
Towbin JA. Pediatric myocardial disease. Pediatr Clin North Am 1999; 46: 289–312.Google Scholar
Badorff C, Lee GH, Lamphear BJ, et al. Enteroviral protease 2A cleaves dystrophin: evidence of cytoskeletal disruption in an acquired cardiomyopathy. Nat Med 1999; 5: 320–326.Google Scholar
Sakamoto A, Ono K, Abe M, et al. Both hypertrophic and dilated cardiomyopathies are caused by mutation of the same gene, delta-sarcoglycan, in hamster: an animal model of disrupted dystrophin-associated glycoprotein complex. Proc Natl Acad Sci USA 1997; 94: 13873–13878.Google Scholar
Mogensen J, Klausen IC, Pedersen AK, et al. Alpha-cardiac actin is a novel disease gene in familial hypertrohic cardiomyopathy. J Clin Invest 1999; 103: R39–R43.Google Scholar