FIG 59.1 Typical electrocardiogram of a patient with Pompe disease demonstrates striking biventricular hypertrophy FIG 59.2 Typical echocardiographic findings in glycogen storage disease type II (A) Diastolic frame in long axis reveals severe concentric left ventricular hypertrophy, while the systolic frame from the same child (B) shows the absence of subaortic obstruction The complete clinical picture together with the characteristic electrocardiographic and echocardiographic findings will lead immediately to the definitive diagnostic investigation This is the demonstration of deficiency of lysosomal α-1,4-glucosidase in fibroblasts grown from a skin biopsy Sometimes the skeletal muscle abnormalities are less evident The presentation is then as a cardiomyopathy alone Pompe disease should be considered in any such case and skin biopsy performed Until recently there was no specific treatment available, and supportive and decongestive measures failed to improve outcomes However, recent studies using recombinant human lysosomal acid α-glucosidase show promise in improving survival.9 Early diagnosis, typically via standardized newborn screening in developed countries, and early initiation of enzyme replacement therapy shows the most benefit.10 Since the disease appears to be inherited in an autosomal recessive fashion, parents should be advised of the availability of prenatal diagnosis via culture of amniocytes obtained by amniocentesis Danon disease is included in this section because it was previously considered to be a variant of Pompe disease known as glycogen storage disease type IIb, with normal acid maltase The disease is due to a deficiency of lysosomeassociated protein 2 (lamp-2) and manifests as a progressive hypertrophic cardiomyopathy with skeletal myopathy Other similar diseases in this family of autophagic vacuolar myopathies are still being studied Some demonstrate autosomal recessive inheritance, whereas others are x-linked, and the degree of cardiac and skeletal involvement is variable.11 Glycogen Storage Disease Type III (Cori Disease, Amylo-1,6-Glucosidase [Debrancher] Deficiency) In Cori disease, an autosomal recessive condition, glycogen accumulates in skeletal muscle, the liver, and cardiac muscle due to a deficiency of amylo-1,6glucosidase, the enzyme necessary for breaking down branch points in glycogen chains There are three subtypes, which are dependent on the primary site of abnormal glycogen storage (IIIa, liver and muscle; IIIb, liver; IIIc, muscle).12 A fourth subtype (IIId) involves normal debrancher enzyme activity but a deficiency of debrancher enzyme transferase activity.13 Patients with types IIIa and c have a tendency to develop skeletal muscle weakness and left ventricular hypertrophy,14 which is progressive A study found that 58% of patients with glycogen storage disease IIIa had some degree of ventricular hypertrophy.15 However, the clinical course appears to be less severe, with fewer symptoms, as compared with hypertrophic obstructive cardiomyopathy.16,17 Glycogen Storage Disease Type IV (Andersen Disease, α-1,4-Glucan-6-Glucosyltransferase [Brancher] Deficiency) Andersen disease is a rare heterogeneous glycogen storage disease characterized by the deposition of glycogen of abnormal structure in the liver, leading to cirrhosis There may also be deposition of glycogen in the heart Consequently, although liver dysfunction is the most common clinical manifestation, the disease can rarely present with dilated cardiomyopathy, which is typically severe.18–21 Glycogen Storage Disease Type V (McArdle Disease, Muscle Phosphorylase Deficiency) McArdle disease is an autosomal recessive condition that results from a deficiency of muscle glycogen phosphorylase It is often not diagnosed until adolescence or adult life and is commonly misdiagnosed in childhood.22 Its main clinical features are muscle fatigability, muscle cramps, and myoglobinuria Rare lethal variants have been reported in infants,23 but the heart is typically spared This may be due to activity of a distinct cardiac phosphorylase isozyme that retains activity in patients with deficiency of the skeletal isozyme.24 No clinical cardiac manifestations have been reported, but on occasion the electrocardiogram (ECG) has features similar to those seen in Pompe disease.25 Glycogen Storage Disease Type VI (Hers Disease, Phosphorylase B Kinase Deficiency, or Liver Phosphorylase Deficiency) Hers disease involves both x-linked and autosomal recessive modes of inheritance and results from deficiency of liver phosphorylase Both have involvement of the liver in childhood, whereas involvement of muscles occurs in