Metabolic Disorders

Phenylketonuria (PKU)

PKU is a genetic disorder in which the body cannot process the amino acid phenylalanine, a building block of proteins found in most foods. Every child born in the U.S. must be screened for PKU. This is good, because babies left untreated through a low-protein diet develop severe mental retardation by adolescence. Special formulas are available for newborns, and for older children and adults there are foods such as low-protein breads, pastas, and cereals. A special formula free of phenylalanine is also necessary to ensure people with PKU get the vitamins and minerals they need. Decline in IQ will occur, even in adults, if adherence to a strict diet is not maintained. In pregnant women or women with PKU who plan to become pregnant, a phenylalanine level below 6-10mg/dL should be maintained to avoid mental retardation in the child.

Methylmalonic Acidemia (MMA)

Also known as Methylmalonic CoA Mutase Deficiency, MMA is a genetic disease that occurs in about 50,000 to 100,000 live births. Symptoms of Methylmalonic Acidemia usually begin in the first few months of life and include lethargy, failure to thrive, vomiting, dehydration, respiratory distress, decreased muscle tone, and an enlarged liver. Acute episodes may include drowsiness, coma, and seizures, with subsequent developmental delays. Treatment of MMA includes a low protein diet and/or restriction of the amino acids isoleucine, valine, and threonine. In addition to food supplementation, carnitine supplementation may also be necessary.

Maple Syrup Urine Disease (MSUD)

MSUD occurs in 1 of 180,000 newborns in the U.S. and is an autosomal recessive disorder. An enzyme defect in the breakdown of the branched-chain amino acids leucine, isoleucine, and valine leads to encephalopathy and progressive neurodegeneration in infants not properly treated for MSUD. The most common form of MSUD will present within 4-7 days of birth as poor feeding, vomiting, poor weight gain, and increasing lethargy, poor muscle tone, and even seizures. A characteristic burned sugar smell of the infant's urine gives the disease its name. The symptoms of MSUD usually worsen when the affected person is sick, has surgery, or is injured, and hospitalization is usually required. Lifelong restriction of leucine, isoleucine, and valine is the only treatment to prevent MSUD symptoms. There are a number of other branched chain amino acid disturbances with similar symptoms and treatment.

Urea Cycle Disorders

Urea cycle disorders comprise many inherited diseases, all related to a deficiency in a particular enzyme in the urea cycle, the pathway in the liver that converts proteins into urea to be excreted in the urine. The disorders may present in neonates or later in life with an earlier onset of symptoms correlated with a more severe deficiency. The urea cycle disorders cause similar symptoms such as lethargy, vomiting, poor feeding in infants, and seizures. Ammonia build up in the brain can cause permanent damage, leading to decline in mental capacity, seizures, or psychoses.

Galactosemia

Classical galactosemia is a genetic disorder affecting carbohydrate metabolism in about 1 in 30,000 births in the U.S. The body is unable to convert the sugar galactose to glucose. Galactose is a breakdown product of lactose, found in dairy products. Three enzymes in the liver are required to complete its conversion to glucose. Patients with galactosemia lack one of those necessary enzymes called galatose-1-phosphate uridyl transferase. If left undetected through newborn screening, jaundice, diarrhea, and vomiting develop soon after birth. Long-term complications include liver disease, cataracts, ovarian failure in females, and even death. The patient may be required to eliminate the sugars lactose and galactose completely from their diet for life, starting with a soy-based formula in infancy.

Lysinuric Protein Intolerance (LPI)

LPI is a metabolic disorder affecting amino acid transport. The disorder occurs most often in Finland (1 in 60,000 births) and Japan (1 in 57,000 births). Specifically, the amino acids ornithine, arginine, and lysine become depleted in the body due to the inability to digest and utilize them. Symptoms of the disease develop as babies are weaned from formula and begin eating more protein-rich solid foods. Signs and symptoms include an enlarged spleen and liver, short stature, muscle weakness, declining immune function, cognitive decline, and progressively worsening osteoporosis. Proteins may also deposit in the lungs, which can be life threatening. Treatment may include a protein-restricted diet and a neutral amino acid supplement called citrulline. With proper diet control and supplementation the patient may obtain strict control of this disorder.

Very Long-Chain Acyl-Coenzyme A Deficiency (VLCAD)

VLCAD affects 1 in 40,000 to 120,000 people in the United States.  VLCAD is caused by a mutation of the gene responsible for the enzyme for which the disease is named.  With a deficiency in activity, fats cannot be converted into energy to be used by the body and very long-chain fatty acids accumulate, causing problems with the liver, heart, and muscles.  Initial signs and symptoms during infancy and childhood include hypoglycemia, lethargy, and muscle weakness.  Serious complications may occur such as liver abnormalities and life-threatening heart problems.  Symptoms appearing during adolescence and adulthood tend to be mild and rarely involve the heart.  Carriers of this autosomal recessive disorder generally do not show signs and symptoms of the condition.  Treatment of VLCAD usually consists eating frequently and use of IV glucose when food cannot be tolerated.  Intake of long-chain fatty acids should be avoided; therefore, special foods and formulas are often required to properly treat the condition. Supplemental carnitine is recommended for some affected children.

Glutaric Acidemia I

Also known as Glutaryl-CoA Dehydrogenase Deficiency, this  organic acidemia is an autosomal recessive disorder, with fewer than 100 known cases in the United States.  This disorder is characterized by neuronal damage and subsequent gliosis (accumulation of astrocytes leading to scar tissue).  This presents as a progressive movement disorder within the first year of life, usually beginning at six months.  A low protein diet consisting of special foods and formulas, and the avoidance of fasting are the mainstays of treating this disorder.  Supplemental carnitine and riboflavin (vitamin B-2) also aids in preventing metabolic crises.