Inborn Errors of Metabolism
QUICK LOOK AT THE CHAPTER AHEAD
Inborn errors of metabolism (IEMs), first described in 1908, are disorders caused by single faulty genes resulting in the inability of the normal metabolic pathway to function and correctly synthesize or breakdown proteins, carbohydrates, or fats. For successful metabolism to occur enzymes and transport proteins are needed. Enzymes are specific proteins that increase or decrease the speed of a chemical reaction but do not change themselves. The substances upon which enzymes exert their effects are called substrates. Once the enzyme has changed the substrate, a product is formed.
This chapter explores common pediatric inborn errors of metabolism.
A well-functioning metabolic pathway depends on many complex sequences of reactions. The child with an IEM may be missing an enzyme, leading to a buildup of substrates that may affect distant organs or may only produce a small amount of product.
Signs and symptoms of IEM may be mild or severe (Table 35-1). Treatment for IEM includes avoiding enzyme substrates in the diet, using medication to remove substrates, replacing a missing product, or providing missing enzymes. Research is focused on gene replacement therapy. Genetic counseling is recommended.
Signs and symptoms of IEM may be mild or severe.The newborn with an IEM may feed poorly, vomit, be lethargic or jittery, and have seizures, acidosis, and jaundice. Laboratory tests include electrolytes, ammonia level, glucose level, urine pH and ketones,
and sometimes analysis of serum/urine/cerebrospinal fluid to detect enzymes, substrates, or products. The newborn with an elevated blood ammonia level usually has acidosis, anorexia, irritability, vomiting, lethargy, seizures, and coma.
and sometimes analysis of serum/urine/cerebrospinal fluid to detect enzymes, substrates, or products. The newborn with an elevated blood ammonia level usually has acidosis, anorexia, irritability, vomiting, lethargy, seizures, and coma.
Table 35-1 Signs and Symptoms Suggesting IEMs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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All states now screen newborns for phenylketonuria (PKU) and hypothyroidism. Most states screen for galactosemia, and some test for other IEM. Screening tests are not diagnostic, and false negatives or false positives may occur.
Screening tests are not diagnostic, and false negatives or false positives may occur.
EXAMPLES OF IEMGalactosemia
Galactosemia is a disorder of carbohydrate metabolism; it is autosomal recessive and occurs in 1 in 40,000 live births. Details of this disorder with screening tests and treatment are as follows:
Screening: Routine newborn screening → Beutler test (looks for enzyme deficiency in red blood cells) or by increased serum galactose.
Cause: Deficiency of one of three liver enzymes needed to convert galactose to glucose → galactose-1-phosphate uridyltransferase (GALT) → galactose and glucose result from the digestion of lactose, a sugar found in dairy products. Accumulation of galactose-1-phosphate in the eyes, liver, brain, and renal tubules causes damage to the eyes, brain, liver, and kidneys.
Result: Susceptibility to gram-negative sepsis, hepatic disease, mental retardation (irreversible), renal disease, cataracts, and ovarian failure.
Signs and symptoms: Slow intrauterine growth, hypoglycemia, vomiting and weight loss within a few days of birth, jaundice, hepatomegaly, enlarged spleen (from portal hypertension),
cirrhosis, speech/language deficits, Escherichia coli sepsis, and malnutrition.
Treatment: Lifelong galactose-free diet, which means no milk or milk products, garbanzo beans, cheese, sherbet, sour cream, yogurt, ice cream, and organ meats. Soy protein formula is used in place of commercial formula or breast milk.
Galactose and glucose result from the digestion of lactose, a sugar found in dairy products.Fatty Acid Oxidation (Breakdown of Fats) Disorders
Fatty acid oxidation disorders, among the most common of the IEMs, manifest as the inability to use fat for energy when glucose stores are low or during sleep. They are autosomal recessive. Details of this disorder with screening tests and treatment are as follows:
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