TY - JOUR
T1 - From discrete dilated cardiomyopathy to successful cardiac transplantation in congenital disorders of glycosylation due to dolichol kinase deficiency (DK1-CDG)
AU - Kapusta, Livia
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, Eva
PY - 2013/3/1
Y1 - 2013/3/1
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.
AB - 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.
KW - CDG-Im
KW - Cardiac transplantation
KW - Congenital disorders of glycosylation
KW - Dilated cardiomyopathy
KW - Dolichol kinase deficiency
KW - Heart failure
UR - http://www.scopus.com/inward/record.url?scp=84879464716&partnerID=8YFLogxK
U2 - 10.1007/s10741-012-9302-6
DO - 10.1007/s10741-012-9302-6
M3 - Article
AN - SCOPUS:84879464716
SN - 1382-4147
VL - 18
SP - 187
EP - 196
JO - Heart Failure Reviews
JF - Heart Failure Reviews
IS - 2
ER -