Table 1.

Inborn errors of metabolism associated with myopathy

lEMs Associated with Myopathy	Inheritance	Clinical Phenotype
Defects in energy metabolism
Carnitine shuttle defects
Primary systemic carnitine deficiency	AR	HCM, hypotonia, muscle weakness, fatigue
Carnitine palmitoyl transferase deficiency type 2 (CPT2) deficiencyb	AR	Muscle weakness, rhabdomyolysis, exercise intolerance (isolated muscle phenotype), CM, hepatomegaly, hypoglycemia, seizures, cystic kidneys (severe infantile)
Carnitine acylcarnitine translocase (CACT) deficiency	AR	CM, arrhythmias, muscle damage, hepatomegaly, hypoglycemia
FAODs
VLCAD deficiencyb	AR	HCM, arrhythmias, sudden death, muscle weakness, exercise intolerance, recurrent rhabdomyolysis, hypoketotic hypoglycemia, “Reye-like” hepatic syndrome
LCHAD deficiencyb	AR	Sudden death, “Reye-like” hepatic syndrome, hypoketotic hypoglycemia, myopathy, recurrent rhabdomyolysis, CM, retinopathy
TFP deficiencyb	AR	Sudden death, “Reye-like” hepatic syndrome, hypoketotic hypoglycemia, CM, recurrent, rhabdomyolysis, peripheral neuropathy
MAD deficiency	AR	Muscle weakness, CM, hypoglycemia, hepatopathy, respiratory dysfunction, encephalopathy, acidosis
Mitochondrial respiratory chain defects
Respiratory chain complexes I-V	AR	Myopathy, CM, hepatopathy, Leigh syndrome, epilepsy, developmental delay ± lactic acidosis
Coenzyme Q deficiency		Myopathy, proteinuria, ataxia, low tissue Coenzyme Q, corrected by Coenzyme Q supplementation
Mitochondrial disorders with mt DNA mutations
Mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes (MELAS)	Mitochondrial	MELAS
Myoclonic epilepsy with ragged-red fibers (MERRF)		MERRF
Neurogenic muscular weakness, ataxia, retinitis pigmentosa (NARP)		NARP
Kearns-Sayre syndrome		CHB, muscle weakness, ataxia, ophthalmoplegia
Disorders of glycogen metabolism
Glycogen storage disease type 3a (Cori disease; debrancher deficiency)	AR	Hepatomegaly, ketotic hypoglycemia, muscle weakness, CM, growth retardation, liver cirrhosis, hepatocellular carcinoma (adulthood)
Glycogen storage disease type 5 (McArdle disease; myophosphorylase deficiency)b	AR	Exercise intolerance (2nd wind phenomena), muscle weakness, exercise-induced rhabdomyolysis
Glycogen storage disease type 7 (Tarui disease; phosphofructokinase deficiency)b	AR	Exercise intolerance (out of wind), muscle weakness, rhabdomyolysis, infantile CM, mild macrocytic anemia
Glycogen storage disease type 9d (muscle phosphorylase kinase deficiency)b	XL	Exercise intolerance, muscle weakness and atrophy, hepatomegaly
lEMs with possible secondary energy defect, carnitine deficiency
Propionic aciduria	AR	DCM, long QT, abnormal respiratory complex in cardiac and skeletal muscle, lactic acidosis, hyperammonemia, DD, low carnitine if not supplemented, hypotonia
Methylmalonic aciduria	AR	Hypotonia, lactic acidosis, hyperammonemia, DD, low carnitine if not supplemented
Other lEMs with myopathy
GSD II (Pompe disease; acid maltase deficiency)a	AR	Infantile DCM, myopathy, atrophy, diaphragmatic weakness (lysosomal storage defect)
GSD IV (Anderson disease; brancher deficiency)	AR	Hepatomegaly, CM, muscle weakness, atrophy, neuromuscular disease, adult isolated myopathy
Danon disease (LAMP2-related)a	XD	HCM, DCM, short PR, WPW, isolated cardiac variants, proximal muscle weakness (85%)
Congenital disorders of glycosylation N- and O-linked disorders	AR	Multisystem disorder, including brain muscle eye disease, CM, limb girdle muscular dystrophy (O-mannosylation defects), hypotonia, liver disease, (N-linked)

Abbreviations: AR, autosomal recessive; CHB, congenital heart block; CHF, congestive heart failure; CM, cardiomyopathy; DCM, dilated cardiomyopathy; DD, developmental delay; HCM, hypertrophic cardiomyopathy; RCM, restrictive cardiomyopathy; WPW, Wolff-Parkinson-White; XD, X-linked dominant; XL, X-linked recessive.

^aClassified also as a lysosomal storage disease.

^bConditions associated with the risk of recurrent rhabdomyolysis.