From discrete dilated cardiomyopathy to successful cardiac transplantation in congenital disorders of glycosylation due to dolichol kinase deficiency (DK1-CDG)

Livia Kapusta, Nili Zucker, George Frenckel, Benjamin Medalion, Tuvia Ben Gal, Einat Birk, Hanna Mandel, Nadim Nasser, Sarah Morgenstern, Andreas Zuckermann, Dirk J. Lefeber, Arjen De Brouwer, Ron A. Wevers, Avraham Lorber, Eva Morava-Kozicz

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Congenital disorders of glycosylation are a growing group of inborn errors of protein glycosylation. Cardiac involvement is frequently observed in the most common form, PMM2-CDG, especially hypertrophic cardiomyopathy. Dilated cardiomyopathy, however, has been only observed in a few CDG subtypes, usually with a lethal outcome. We report on cardiac pathology in nine patients from three unrelated Israeli families, diagnosed with dolichol kinase deficiency, due to novel, homozygous DK1 gene mutations. The cardiac symptoms varied from discrete, mild dilation to overt heart failure with death. Two children died unexpectedly with acute symptoms of heart failure before the diagnosis of DK1-CDG and heart transplantation could take place. Three other affected children with mild dilated cardiomyopathy at the time of the diagnosis deteriorated rapidly, two of them within days after an acute infection. They all went through successful heart transplantation; one died unexpectedly and 2 others are currently (after 1-5 years) clinically stable. The other 4 children diagnosed with mild dilated cardiomyopathy are doing well on supportive heart failure therapy. In most cases, the cardiac findings dominated the clinical picture, without central nervous system or multisystem involvement, which is unique in CDG syndrome. We suggest to test for DK1-CDG in patients with dilated cardiomyopathy. Patients with discrete cardiomyopathy may remain stable on supportive treatment while others deteriorate rapidly. Our paper is the first comprehensive study on the phenotype of DK1-CDG and the first successful organ transplantation in CDG syndrome.

Original languageEnglish (US)
Pages (from-to)187-196
Number of pages10
JournalHeart Failure Reviews
Volume18
Issue number2
DOIs
StatePublished - Mar 1 2013
Externally publishedYes

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Congenital Disorders of Glycosylation
Dilated Cardiomyopathy
Heart Transplantation
Heart Failure
Hypertrophic Cardiomyopathy
Organ Transplantation
Cardiomyopathies
Glycosylation
Dilatation
Central Nervous System
Pathology
Phenotype
Mutation
Type Im Congenital Disorder of Glycosylation
Therapeutics
Infection
Genes

Keywords

  • Cardiac transplantation
  • CDG-Im
  • Congenital disorders of glycosylation
  • Dilated cardiomyopathy
  • Dolichol kinase deficiency
  • Heart failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

From discrete dilated cardiomyopathy to successful cardiac transplantation in congenital disorders of glycosylation due to dolichol kinase deficiency (DK1-CDG). / Kapusta, Livia; Zucker, Nili; Frenckel, George; Medalion, Benjamin; Gal, Tuvia Ben; Birk, Einat; Mandel, Hanna; Nasser, Nadim; Morgenstern, Sarah; Zuckermann, Andreas; Lefeber, Dirk J.; De Brouwer, Arjen; Wevers, Ron A.; Lorber, Avraham; Morava-Kozicz, Eva.

In: Heart Failure Reviews, Vol. 18, No. 2, 01.03.2013, p. 187-196.

Research output: Contribution to journalArticle

Kapusta, L, Zucker, N, Frenckel, G, Medalion, B, Gal, TB, Birk, E, Mandel, H, Nasser, N, Morgenstern, S, Zuckermann, A, Lefeber, DJ, De Brouwer, A, Wevers, RA, Lorber, A & Morava-Kozicz, E 2013, 'From discrete dilated cardiomyopathy to successful cardiac transplantation in congenital disorders of glycosylation due to dolichol kinase deficiency (DK1-CDG)', Heart Failure Reviews, vol. 18, no. 2, pp. 187-196. https://doi.org/10.1007/s10741-012-9302-6
Kapusta, Livia ; Zucker, Nili ; Frenckel, George ; Medalion, Benjamin ; Gal, Tuvia Ben ; Birk, Einat ; Mandel, Hanna ; Nasser, Nadim ; Morgenstern, Sarah ; Zuckermann, Andreas ; Lefeber, Dirk J. ; De Brouwer, Arjen ; Wevers, Ron A. ; Lorber, Avraham ; Morava-Kozicz, Eva. / From discrete dilated cardiomyopathy to successful cardiac transplantation in congenital disorders of glycosylation due to dolichol kinase deficiency (DK1-CDG). In: Heart Failure Reviews. 2013 ; Vol. 18, No. 2. pp. 187-196.
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abstract = "Congenital disorders of glycosylation are a growing group of inborn errors of protein glycosylation. Cardiac involvement is frequently observed in the most common form, PMM2-CDG, especially hypertrophic cardiomyopathy. Dilated cardiomyopathy, however, has been only observed in a few CDG subtypes, usually with a lethal outcome. We report on cardiac pathology in nine patients from three unrelated Israeli families, diagnosed with dolichol kinase deficiency, due to novel, homozygous DK1 gene mutations. The cardiac symptoms varied from discrete, mild dilation to overt heart failure with death. Two children died unexpectedly with acute symptoms of heart failure before the diagnosis of DK1-CDG and heart transplantation could take place. Three other affected children with mild dilated cardiomyopathy at the time of the diagnosis deteriorated rapidly, two of them within days after an acute infection. They all went through successful heart transplantation; one died unexpectedly and 2 others are currently (after 1-5 years) clinically stable. The other 4 children diagnosed with mild dilated cardiomyopathy are doing well on supportive heart failure therapy. In most cases, the cardiac findings dominated the clinical picture, without central nervous system or multisystem involvement, which is unique in CDG syndrome. We suggest to test for DK1-CDG in patients with dilated cardiomyopathy. Patients with discrete cardiomyopathy may remain stable on supportive treatment while others deteriorate rapidly. Our paper is the first comprehensive study on the phenotype of DK1-CDG and the first successful organ transplantation in CDG syndrome.",
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AU - Zucker, Nili

AU - Frenckel, George

AU - Medalion, Benjamin

AU - Gal, Tuvia Ben

AU - Birk, Einat

AU - Mandel, Hanna

AU - Nasser, Nadim

AU - Morgenstern, Sarah

AU - Zuckermann, Andreas

AU - Lefeber, Dirk J.

AU - De Brouwer, Arjen

AU - Wevers, Ron A.

AU - Lorber, Avraham

AU - Morava-Kozicz, Eva

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N2 - Congenital disorders of glycosylation are a growing group of inborn errors of protein glycosylation. Cardiac involvement is frequently observed in the most common form, PMM2-CDG, especially hypertrophic cardiomyopathy. Dilated cardiomyopathy, however, has been only observed in a few CDG subtypes, usually with a lethal outcome. We report on cardiac pathology in nine patients from three unrelated Israeli families, diagnosed with dolichol kinase deficiency, due to novel, homozygous DK1 gene mutations. The cardiac symptoms varied from discrete, mild dilation to overt heart failure with death. Two children died unexpectedly with acute symptoms of heart failure before the diagnosis of DK1-CDG and heart transplantation could take place. Three other affected children with mild dilated cardiomyopathy at the time of the diagnosis deteriorated rapidly, two of them within days after an acute infection. They all went through successful heart transplantation; one died unexpectedly and 2 others are currently (after 1-5 years) clinically stable. The other 4 children diagnosed with mild dilated cardiomyopathy are doing well on supportive heart failure therapy. In most cases, the cardiac findings dominated the clinical picture, without central nervous system or multisystem involvement, which is unique in CDG syndrome. We suggest to test for DK1-CDG in patients with dilated cardiomyopathy. Patients with discrete cardiomyopathy may remain stable on supportive treatment while others deteriorate rapidly. Our paper is the first comprehensive study on the phenotype of DK1-CDG and the first successful organ transplantation in CDG syndrome.

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