Table 1.

Induced pluripotent stem cell models of cardiomyopathies associated with inborn errors of metabolism

Disease	Year (Ref)	Specific mutation	iPSC-CM in vitro phenotype	Cardiac muscle clinical phenotype
Glycogen Storage disorder
Pompe Disease (Type II)	2011 (17)	Unspecified GAA gene mutations	Lysosomal glycogen accumulation; increased autophagosome structures; mitochondrial dysfunction	Hypertrophy, hyperdynamic systolic function with outflow obstruction
	2014 (18)	Compound heterozygote mutations: [del ex18] exon 18 deletion and [del525T] single nucleotide exon 2 deletion in GAA gene Compound heterozygote mutation: (IVS1-13T>G) and deletion of exon 18 in GAA gene	Elevated lysosomal glycogen; larger glycogen granules observed in infantile compared to late onset PD iPSC-CMs
	2015 (19)	Homozygous exon 18 deletion in GAA Heterozygous exon 18 deletion in GAA	Lysosomal glycogen accumulation; autophagic dysfunction - autophagosome accumulation and higher electrophoretic mobility of lysosome-associated membrane proteins
	2015 (20)	Heterozygous mutation c.796C>T and c.1316T>A in GAA	Lysosomal glycogen accumulation
Danon Disease (Type IIb)	2015 (21)	2 base pair insertion in exon 2 of LAMP-2 gene (129-130 insAT) Single point mutation in intron 1 of LAMP-2 gene (IVS-1 c.64+1 G>A)	Increased early autophagic vacuoles, lack of mature autophagic vacuoles; Heart failure feature: cellular hypertrophy; Oxidative stress features: fragmented, short mitochondria, poor mitochondrial network	Hypertrophy, reduced ejection fraction, and altered calcium handling consistent with heart failure
Mitochondrial disease
Barth Syndrome	2011 (22)	Missense mutation in TAZ1 gene (590G>T) Splice site mutation in TAZ1 gene (110-1AG>AC) Missense mutation in TAZ1 (170G>T)	Impaired cardiolipin remodeling: absent mature CL and accumulation of precursor, MLCL; decreased respiratory chain supercomplex formation; altered mitochondrial oxygen consumption; increased ROS CM differentiation unsuccessful due to cell death	Dilated cardiomyopathy
	2014 (23)	Frameshift mutation in TAZ gene (c.517delgG) Missense mutation in TAZ gene (c.328T>C)	Impaired cardiolipin remodeling; lower ATP levels; impaired sarcomerogenesis; defective contractility
Lysosomal storage disease
Fabry disease	2013 (24)	Hemizygous mutation in exon 3 of GLA gene c.485G>A	Membranous cytoplasmic bodies in lysosomes CM differentiation unsuccessful due to cell death	Hypertrophic cardiomyopathy, left ventricular hypertrophy, systolic and diastolic dysfunction, arrhythmias
	2014 (25)	Hemizygous mutation in exon 3 of GLA gene c.485G>A Hemizygous mutation in exon 5 of GLA gene c.658C>T	Lysosomal globotriaosylceramide accumulation; electron dense storage inclusions (zebra bodies); disorganized contractile fibers with peripheral localization