Metabolism is the process the body uses to make the energy that powers all bodily functions, including movement, breathing, digestion, heartbeat, blood circulation, nerve impulses, cell growth and repair, and regulation of body temperature and hormone levels. This involves many chemical reactions in the body that convert nutrients (sugars/carbohydrates, protein/amino acids, fat/lipids, vitamins, and minerals) from our food into energy. Metabolic disorders occur when there is dysfunction in any step of one of these chemical reactions, usually due to an enzyme or hormone deficiency or organ dysfunction. There are hundreds of known metabolic disorders, which are categorized according to the specific nutrient(s) whose metabolism is disrupted, whether there is a deficiency of an enzyme or substance, or a build-up of a substance due to the body’s inability to break it down (catabolism). Most of these disorders are inherited, meaning they are due to genetic issues passed from parent to child. Specific types of metabolic disorders include Metabolic Syndrome, Amino Acid Metabolism Disorders, Carbohydrate Metabolism Disorders, Lipid Metabolism Disorders, Metal Metabolism Disorders, Mitochondrial Disorders, and Peroxisomal/Lysosomal Storage Disorders.
Treatment of metabolic disorders varies widely by the type of disorder. Often, treatment will require specialized diets that avoid nutrients the body may not be able to metabolize, or patients with certain metabolic disorders may be able to take a medication or supplement to replace an enzyme or chemical that is low or absent in the body. Other treatment options include supportive care to control symptoms that may be present in metabolic disorders, and therapies that remove excess by-products of metabolism that the body is unable to remove on its own. Unfortunately, some metabolic disorders are so severe that they are fatal, resulting in sometimes significantly decreased life expectancy. Not all metabolic disorders can be treated with medications, but there are pharmacologic treatment options available for many of them.
Metabolic Syndrome is unique among metabolic disorders, in that it is not an inherited deficiency of a specific chemical or enzyme, but a combination of conditions that occur together, which increase the risk of heart disease, type 2 diabetes, and stroke. These conditions include increased abdominal fat/waist circumference, increased blood pressure, high blood sugar, and abnormal cholesterol and/or triglyceride levels. The recommended treatment is lifestyle changes, including physical activity, a healthy diet, weight loss, quitting smoking, and stress-reducing techniques. When lifestyle changes alone are not sufficient, patients with metabolic syndrome may be prescribed medications to help lower blood pressure and blood sugar and to regulate cholesterol/triglyceride levels. Medications to lower blood pressure include ACE inhibitors (ex.- lisinopril, benazepril, captopril), angiotensin receptor blockers (ARBs) (ex.- losartan, candesartan, valsartan), diuretics (ex.- hydrochlorothiazide/HCTZ, spironolactone, triamterene, furosemide), and beta-blockers (ex.- metoprolol, carvedilol, atenolol).
Lipid Metabolism Disorders (ex.- Familial Hypercholesterolemia, Neimann-Pick Disease, Tay-Sachs Disease) cause increased (most common) or decreased levels of lipids/fats in the body. This is usually measured by levels of cholesterol (low-density lipoprotein/LDL, or “bad” cholesterol, and high-density lipoprotein/HDL or “good” cholesterol) or triglycerides in the blood. Lipids are an important part of cell membranes in the body, so low levels can cause functional problems in the body, but high levels of lipids can cause build-up in the veins, arteries, heart, and nerves, significantly increasing the risk of stroke and heart attack. Available medication therapies for lipid metabolism disorders typically work to decrease levels of cholesterol and triglycerides in the blood. Statins (ex.- simvastatin, atorvastatin, pravastatin, rosuvastatin) work by decreasing cholesterol synthesis in the liver. Bile acid sequestrants (ex.- cholestyramine, colestipol, colesevelam) work by binding to cholesterol in the gut to remove it from the body. Ezetimibe prevents cholesterol absorption into the small intestine. PSCK9 Inhibitors (ex.- evolocumab, alirocumab) bind to a protein in the liver to inactivate it and reduce LDL cholesterol. Fibrates (ex.- fenofibrate, gemfibrozil) work in the liver to lower the production of triglycerides and remove LDL. Niacin is a B-vitamin that can help improve all lipid levels (LDL, HDL, cholesterol). Omega-3 Fatty Acids/Fish Oil block the synthesis of triglycerides.
Amino Acid Metabolism Disorders (ex.- Homocystinuria, Maple Syrup Urine Disorder, Tyrosinemia, Phenylketonuria, Citrullinemia, Carnitine Deficiency, Argininosuccinic Aciduria) are inherited diseases that either inhibit the body’s ability to break down or to absorb and use amino acids. Amino acids make up proteins, which are necessary for most body processes and functions. The body can make some amino acids, while others must be taken in through food. Most of these disorders are diagnosed in infancy. Treatment usually consists of a specialized diet, such as one low in protein, or with elemental feeding formulas that do not contain the amino acid the disorder is related to. Supplementation with B vitamins (ex.- thiamine/B1, pyridoxine/B6, cobalamin/B12, folic acid/B9, biotin/B7), which are an essential part of coenzymes and cofactors in amino acid metabolism, helps improve symptoms in some patients with these disorders. Sapropterin is a medication used in phenylketonuria that helps patients tolerate phenylalanine. Several amino acid metabolism disorders can cause a build-up of ammonia, leading to life-threatening symptoms. Ammonia levels can be decreased using oral lactulose and IV sodium benzoate, arginine, and sodium phenylbutyrate. IV dextrose and glucose can also help to regulate levels of amino acids in the blood.
Carbohydrate Metabolism Disorders (ex.- Galactosemia, Glycogen Storage Diseases, Hunter Syndrome) inhibit the body’s ability to make (anabolism) or break down (catabolism) sugars/carbohydrates. The simple sugar that cells need to create energy is glucose. Treatment of these disorders involves avoidance of specific types of sugars and control of blood sugar levels. Many of these diseases can cause hypoglycaemia (low blood sugar), which is treated with oral or IV glucose. IV dextrose solution (D50) or glucagon injections may also be used in severe hypoglycaemia. The type of sugar replacement may depend on whether the patient can convert the carbohydrate to glucose in their body. Dietary changes are the mainstay of treatment, including specialized formulas, and oral corn-starch, which digests slowly and helps keep glucose levels steady in the body. Biotin supplements are also used in some of these disorders.
Metal Metabolism Disorders (ex.- Hemochromatosis, Wilson’s Disease, Porphyria) usually result in a toxic build-up of metals in the body such as copper, iron, zinc, and manganese. Metals are nutrients/trace elements needed in the body for many processes. They are usually managed in the body by specific proteins that may malfunction in metabolic disorders. Treatment usually involves routine phlebotomy, or blood removal, which can remove the overload of metal in the blood. Liver transplantation may sometimes be needed. Medication treatment involves chelators, which bind to metal ions and remove them from the body, or supplementation with metals/trace elements that may be low in some metal metabolism disorders (ex.- zinc acetate, manganese, copper histidinate). Examples of metal chelating medications include desferrioxamine, deferasirox, penicillamine, disodium calcium edetate, and trientine hydrochloride.
Mitochondrial Disorders (ex.-Mitochondrial Disease, Mitochondrial Encephalopathy, MELAS Syndrome) affect how the mitochondria, which are considered the “power house” or energy source of cells, work. Mitochondria may not be able to produce the energy the body needs, which can result in organ dysfunction. This can be particularly problematic when the mitochondria affected are in the muscles, heart, and nervous system. Treatment usually involves symptom treatment depending on the body system affected. For example, patients may need anti-seizure medications if the nervous system is affected. Nutritional supplements such as riboflavin, carnitine, and coenzyme Q10 can be beneficial.
Perosixomal/Lysosomal Storage Disorders (ex.- Krabbe Disease, Gaucher Disease, Zellweger Syndrome) are due to defects in lysosomes or peroxisomes, spaces in cells full of enzymes that break down and eliminate by-products of cell metabolism. These disorders can result in a build-up of toxic substances in the body. One of the main treatments in children is stem cell/bone marrow transplant for many of these diseases. Medication therapy includes enzyme replacement therapy and substrate reduction therapy (medication decreases the number of substances that build up inside the cells). Examples of enzyme replacement therapies include alglucerase injection, imiglucerase, Fabrazyme, and aldurazyme. Miglustat is an oral tablet used as substrate reduction therapy.
Are possible with any medication. Common side effects that are to be expected with many medications include nausea, diarrhoea, drowsiness, dizziness, headache, and injection site reactions such as redness or burning. More serious side effects of specific drugs/drug classes that may require medical attention are discussed below.
Myopathy/Rhabdomyolysis is a rare but serious complication of several treatments for metabolic disorders, particularly cholesterol-lowering medication, that causes muscle fibre breakdown, which releases toxic chemicals into the bloodstream and can cause kidney failure. If you experience muscle pain, stiffness, and weakness, especially if accompanied by dark urine and/or fever, you should seek medical attention right away.
Drug Interactions are common with medications for metabolic disorders, even nutritional supplements and OTC medications. Some metabolic disorders can also affect how certain drugs are metabolized/eliminated in the body. Many of these drug interactions will require a change in therapy, so it is important that your doctor and pharmacist know ALL medications you are taking.
Organ Damage, especially to the liver or kidneys, is possible with several medications. Signs and symptoms of organ damage include decreased urination, abdominal pain, and yellowing of the skin or whites of the eyes. If you have a serious infection that requires long-term treatment, it is important to keep all medical appointments and have regular blood draws, which can often detect abnormal lab values that indicate organ damage before symptoms occur.
Advances in medicine have made metabolic disorders much more manageable than in the past, and many patients can live normal lives with a combination of dietary, medication, and sometimes occupational/physical therapy. Follow-up with a medical provider for routine monitoring, following a strict diet, and taking medications exactly as prescribed is essential for disease management.