the first heart sound is accentuated, and nonspecific systolic murmurs may be present A high incidence of mitral valve prolapse has been reported in adults with Graves disease144,145 but has not been demonstrated in children.146 This suggests that the appearance of the prolapse is related to the duration of the disease The ECG is atypical Sinus tachycardia, first-degree atrioventricular block, and nonspecific ST-segment and T-wave changes may be present Signs of atrial and left ventricular enlargement are more common in children than in adults.147 Although atrial fibrillation is quite common in adults, it is extremely rare in children Radiographic cardiomegaly and a slight increase in pulmonary vascular markings may be seen, especially in the setting of CHF, although this is rare today The echocardiogram reveals hyperdynamic ventricular contractions with a variable degree of chamber enlargement Evaluation of cardiac function by radionuclide angiography in the presence of hyperthyroidism has demonstrated a fall in left ventricular ejection fraction with exercise; however, upon restoration of a normal thyroid state, the ejection fraction shows its normal exercise-induced increase.148 In general the cardiovascular system in childhood tolerates the effects of hyperthyroidism well In the presence of cardiac failure, however, concomitant cardiovascular lesions must be excluded Cardiovascular manifestations of hyperthyroidism are reversible with treatment; but if the disease is of long standing or poorly treated, it may predispose to irreversible cardiac dysfunction.149 Addison Disease Adrenal insufficiency may occur at any age and demonstrates no predilection for gender It usually results from autoimmune destruction of the adrenal cortex and is manifested by weakness, hyperpigmentation, nausea, vomiting, loss of weight, and hypotension When acute in onset or when seen in patients who are metabolically stressed by a concomitant illness, the disease may present with shock or coma Cardiac involvement is due to the chronic hypotension and hypovolemia Chest radiography may demonstrate diminished cardiac size.150 The ECG may demonstrate diffusely low voltages, sinus bradycardia, and first-degree atrioventricular block Treatment involves replacement of mineralocorticoid hormones and must be carried out with caution as CHF can ensue This complication is presumably due to the acute load of salt and water that is thrust upon the previously unloaded myocardium and is a readily treatable, generally transient condition.151 Disorders of Energy Metabolism Mitochondrial Myopathies The mitochondrial myopathies are muscle and systemic disorders characterized by the presence of mitochondria with abnormal structure, number, and/or function They are typically caused by deletions in mitochondrial deoxyribonucleic acid (DNA), although some are caused by defects in nuclear DNA These disorders involve complexes of the respiratory chain and thus affect oxidative phosphorylation Chronic progressive ophthalmoplegia, or Kearns-Sayre syndrome, is frequently encountered among these diseases It is associated with pigmentary degeneration of the retina, lack of coordination, facial and limb weaknesses, short stature, and endocrinologic anomalies The disease appears in childhood and has a progressive course The most frequently reported cardiac anomaly is progressive heart block ECGs should be performed frequently for early recognition and appropriate implantation of a pacemaker.152 Cardiomyopathy, prolonged QT interval, torsades de pointes, atrial arrhythmias, and mitral valvar prolapse have also been described (see further on).153–157 Myoclonic epilepsy with ragged red fibers and mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes can present with a dilated cardiomyopathy.158 Patients with Leigh syndrome, or subacute necrotizing encephalomyelopathy, can develop hypertrophic cardiomyopathy and conduction system defects.159 Mitochondrial deoxyribonucleic acid is maternally transmitted Inheritance, therefore, follows non-Mendelian patterns Barth Syndrome Barth syndrome is an X-linked disorder due to a defect in the TAZ gene, encoding tafazzin, a phospholipid transacylase in the mitochondrial membrane This defect leads to a deficiency of cardiolipin, causing disruption of mitochondrial structure and energy metabolism as well as a deficiency in adenosine triphosphate.160 The disease is characterized by a dilated cardiomyopathy, skeletal myopathy, cyclic neutropenia, and growth retardation The heart typically displays poor contractility and is often hypertrabeculated, showing features of ventricular noncompaction Hypertrophy has also been