muscular atrophy (spinal muscular atrophy type 1, Werdnig-Hoffman disease) is a lethal variant presenting with severe hypotonia and respiratory failure Various congenital heart defects have been reported in patients with this disease, but these are likely chance associations.289,290 Refsum Disease Refsum disease is a rare neurologic disorder due to the accumulation of phytanic acid in peroxisomes Phytanic acid is a branched-chain fatty acid that is partially broken down by phytanoyl-CoA2-hydroxylase, and many cases of the disease are due to defects in the gene encoding this enzyme.291 This leads to the accumulation of phytanic acid in blood and tissues Symptoms appear in the first and second decades of life, and the initial presentation is with weakness, unsteady gait, and night blindness These patients have a diagnostic tetrad: retinitis pigmentosa, peripheral polyneuropathy with diminished or absent deep tendon reflexes, cerebellar ataxia, and high protein levels in cerebrospinal fluid without pleocytosis Other frequent signs are nerve deafness, anosmia, nystagmus, and abnormalities of the pupils The heart is rarely affected Conduction abnormalities, especially advanced degrees of atrioventricular block requiring pacemaker therapy, are well known Cardiomyopathy is a rare association.292 Diets low in phytanic acid produce clinical improvement Complete recovery is rarely obtained, but treatment will slow progression of the disease The association of plasmapheresis with the diet reduces the levels of phytanic acid more rapidly.293 Nutritional Deficiencies Selenium Selenium is a trace element that is an essential component of glutathione peroxidase The enzyme removes organic hydroperoxides from the cell Absence of selenium, possibly associated with absence of vitamin E, permits damage to the cell membrane by lipid peroxides Deficiency of selenium, also known as Keshan disease, affects children living in areas with a poor content of selenium in the soil or those receiving a poor diet.294 It gives rise to an endemic dilated cardiomyopathy that affects children between 1 and 9 years of age living in an area extending from the northeast to the southwest of China, where the content of selenium in the soil and food is very low It has also been reported with nutritional changes related to bariatric surgery295 and with total parenteral nutrition.296 ECG abnormalities—including premature ventricular contractions, QRS widening, and QT prolongation—in asymptomatic patients may predict those at risk for developing chronic Keshan disease.297 The incidence has been significantly reduced by adding oral sodium selenite in the diet, with no adverse side effects Once fully developed, the cardiomyopathy is irreversible298; however, early recognition of the cause of the cardiomyopathy, with timely institution of selenium supplementation, can bring about resolution.299 Histopathologic features of the heart are areas of myocytic loss with replacement fibrosis in the subepicardial surfaces of the ventricles.300 Carnitine L-carnitine, or hydroxy-trimethylammonium butyrate, is an essential cofactor in the transfer of long-chain fatty acids across the inner mitochondrial membrane Depletion of carnitine blocks the mitochondrial oxidation of fatty acids and leads to the cytoplasmic accumulation of lipids Cardiac and skeletal muscles use fatty acids as their main substrate and therefore are very sensitive to carnitine.301 Primary syndromes due to deficiency of carnitine are divided into myopathic and systemic forms Patients with muscular deficiency present with progressive weakness and are thought to have abnormal transport of carnitine into skeletal muscle They have normal levels of carnitine in the plasma but low concentrations in the muscles Hypotheses for the cause of systemic deficiency include defects in synthesis, renal handling, gastrointestinal absorption and cellular transport, and excessive degradation At least some cases have been demonstrated to be due to defects in the carnitine transporter gene.302 Accumulation of triglycerides in muscle often occurs, since fatty acids are not transported effectively into the mitochondria for oxidation Patients often have low concentrations of carnitine in the plasma and tissues, although this is not a sensitive marker for the disease About half of the patients with systemic primary carnitine deficiency present before 2.5 years of age with a metabolic hepatic disorder characterized by encephalopathy, hypoglycemia, and liver dysfunction The presentation is often preceded by fasting or a respiratory illness The remaining patients present at a slightly older age, typically around age 4, with a myopathic (cardiac) disorder characterized by a dilated cardiomyopathy and hypotonia Rarely, patients are not recognized until adulthood.303 Cardiomyopathy has frequently been reported in association with either systemic or myopathic deficiency Many patients are in cardiac failure when they come to medical attention.304 The ECG is nonspecific, with signs of left ventricular hypertrophy Very tall and peaked T waves, like those seen in hyperkalemia, have been described.305 The echocardiogram reveals left ventricular and left atrial dilation with signs of poor left ventricular function The last can also be demonstrated by nuclear angiography Cardiac failure responds poorly to conventional therapy Endocardial fibroelastosis as a result of systemic deficiency has been described.306 The diagnosis is dependent on the demonstration of low levels of carnitine in the tissues or blood, although normal levels do not rule out the disorder Muscle biopsy shows large amounts of lipids in type I muscle fibers and abnormal mitochondria The disease is usually fatal without treatment Oral L-carnitine produces clinical improvement in many patients.307 Others fail to respond to therapy.308 Diarrhea is the main side effect Diets with only 20% of calories from fat are also useful in long-term treatment Carnitine deficiency is inherited in autosomal recessive fashion Thiamine (Beriberi) Thiamine, or vitamin B1, is a water-soluble vitamin that is absorbed from the small intestine In its active form of thiamine pyrophosphate, it is an essential