Glycogen storage diseases (GSD) are disorders in which glycogen cannot be metabolized to glucose because of an abnormality in the enzymes involved in glycogenolysis. The major sites of glycogen deposition are liver and muscle tissue. Clinical manifestations include hypoglycemia, hepatomegaly, poor growth, muscle weakness, cramping, and fatigue. The most common types of GSD that respond to nutritional therapy are GSD type I and GSD type III. The goal of dietary treatment is to prevent hypoglycemia.
Glycogen storage disease type I (glucose-6-phosphatase deficiency) results from a deficiency in the enzyme glucose-6-phosphatase. which is needed for the production of glucose from both glycogenolysis and gluconeogenesis. Biochemical abnormalities include hypoglycemia, hyper-lipidemia. hyperuricemia, and lactic acidemia. Because endogenous glucose production is limited, nutritional therapy involves supplying a constant exogenous source of glucose to prevent hypoglycemia. The diet should be high in complex carbohydrate's, with an energy distribution of 60 to 7()'i carbohydrate. Itlto I5'i protein, and the remainder as fat. Frequent daytime feedings are required. Since patients cannot metaboli/e fructose and galactose, the diet is limited in dairy products, fruits, and simple carbohydrates. Vitamin and mineral supplements arc often necessary.
Continuous overnight nasogastric or gastrostomy feedings are used to prevent nocturnal hypoglycemia. Patients should eat immediately after the overnight feeding has been discontinued. An alternative approach uses oral doses of uncooked cornstarch (I'CS) every 4 to 6 hours to provide a continuous source of glucose. The UCS doses are calculated using 1.75 to 2.5 g/kg body weight per dose. The I'CS is mixed in cool water or a sugar-free beverage. I 'sc of I'CS is not recommended in infants under CJ months of age as pancreatic amylase activity may be insufficient.
Glycogen storage disease type III (dcbrancher enzyme deficiency) results from a deficiency of the enzyme amylo-1,6-glucosidase. Clinical manifestations are generally less severe than in GSD type I and include fasting ketosis. less significant hypoglycemia and hvperlipidemia. and the absence of lactic acidemia and hyperuricemia. These patients are able to synthesize glucose through gluconeogenesis.
Diets high in protein have been advocated to provide adequate substrate for gluconeogenesis. with energy distributions of 25r'< protein. 45':; carbohydrate, and 30'/; fat. Frequent high protein, low carbohydrate feedings arc provided during the day, with a high protein snack at night. Continuous overnight feedings may be necessary in infants and young children.
Fatty Acid Oxidation and Carnitine Transport Defects
Fatty acid oxidation defects arc inborn errors of Catty acid metabolism usually impairing the production of ketones as an energy source tor the brain and other organs. Fatty acid oxidation defects often present following a period of fasting, febrile illness, or increased muscle activity. Features include encephalopathy, hypoketotic hypoglycemia. cardiomyopathy, episodic vomiting, liver dysfunction. and muscle weakness. Age of presentation varies but these defects often occur in infancy.
Defects have been identilied in enzymes involved in the transport of long chain fatty acids by carnitine into the mitochondria as well as in the mitochondrial fatty acid beta-oxidation cycle. Transport defects include carnitine transporter defect (CTD). carnitine-acylcarnitine translo-case deficiency, and carnitine palmitoyl transferase deficiency (CPT I. CPT 2). Identilied defects in mitochondrial fatty acid oxidation include very long chain acyl-CoA dehydrogenase (VLCAD) deficiency, long chain acyl-CoA dehydrogenase (I.CAD) deficiency, medium chain acyl-CoA dehydrogenase (MCAD) deficiency, short chain acyl-CoA dehydrogenase (SCAD) deficiency, multiple acyl-CoA dehydrogenase deficiency (glutaric acidemia type II). long chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency, short chain .Vhydroxyacvl-CoA dehydrogenase (SCHAD) deficiency, and medium chain 3-ketoacyl-CoA thiolase (MCKAT) deficiency. The most common of these disorders. MCAD deficiency, has been associated with sudden infant death syndrome.
The goal of treatment in the acute phase is to provide sufficient glucose to correct hypoglycemia and reduce the need to use ketones as a substrate for energy. Long-term management involves avoidance of prolonged fasting and increased intake of carbohydrate calories during periods of increased energy demand. Frequent meals and snacks that are high in carbohydrate are used during the day. Overnight fasting longer than 6 hours in infants or 8 to 12 hours in children should he avoided. Use of uncooked cornstarch I 1.5 to 2.0 g/kg hotly weight) to delay onset of fasting, or overnight feedings, may be helpful. Low fat diets may be prescribed. In defects of long chain fatty acid oxidation, diets which are restricted in long chain fat can be supplemented with medium chain triglycerides. To prevent essential fatty acid deficiency in low fat diets, linole-ic acid and alpha-linolcnic acid should provide .V/r and \'( of total energy, respectively. Carnitine supplementation is indicated in carnitine transport defects but remains controversial in the management of other fatty acid oxidation defects.
Mitochondrial disorders are a group of diseases that affect mitochondrial energy metabolism. Mitochondrial disorders result in decreased energy production and impaired body functioning. Age of presentation varies. They can affect virtually any organ or tissue and are often multisystem in nature. They are progressive and usually result in significant disabilities. Mitochondrial disorders show a wide range of symptoms, including seizures, developmental delay, autonomic nervous system dysfunction (breathing problems, temperature instability, diarrhea, or pseudoobstruction). cardiomyopathy, hepatic and renal dysfunction. muscle weakness, gastrointestinal dysmotility. endocrine abnormalities such as diabetes, v ision and hearing problems, and poor growth.
Treatment is mainly supportive and is based on individual symptoms. Muscle fatigue, developmental delay, gastroesophageal reflux, and poor oropharyngeal coordination all predispose to poor intake. Undernourished states may produce symptoms that suggest an accelerated deterioration in the status of the patient. Attention to adequate nutrition is essential to maintain optimal growth, development, and level of functioning in these patients.
Carnitine and vitamin supplementation have been used with varying degrees of success. Supplements may include carnitine (SO to 100 mg/kg body weight), coenzyme Q (4.3 mg/kg body weight), vitamin C (SO to 1000 mg). thiamin (100 mg). and riboflavin (100 mg).
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WHAT IT IS A three-phase plan that has been likened to the low-carbohydrate Atkins program because during the first two weeks, South Beach eliminates most carbs, including bread, pasta, potatoes, fruit and most dairy products. In PHASE 2, healthy carbs, including most fruits, whole grains and dairy products are gradually reintroduced, but processed carbs such as bagels, cookies, cornflakes, regular pasta and rice cakes remain on the list of foods to avoid or eat rarely.