Tuesday, April 29, 2008 Metabolic newborn screening program
(Part III)
Galactosemia
LACTOSE is an important source of calories for most babies, whether from breast milk or formula. Lactose, or milk sugar, is made up of two simple sugars: glucose and galactose.
Galactose is found in the diet primarily as lactose in breast milk, milk-based formula, butter, cheese and many nutritional and pharmaceutical extenders.
Galactose is now known to be present in many foods that do not contain lactose, especially beans and peas.
Classic galactosemia is a condition where children lack the enzyme necessary to process galactose. Byproducts of galactose build up in the blood and are toxic to the kidney, liver, ovaries and brain. For babies with galactosemia, lactose then becomes a poison.
Classic galactosemia is a rare recessive genetic disorder. Although the clinicians recognized galactosemia very early in the century, the defective gene that caused it wasn't found until 1956.
Another major breakthrough was when it was first found to be detectable through a newborn screening method in 1963.
Galactosemia is an autosomal recessive genetic trait and is unknowingly passed down from generation to generation. This faulty gene usually emerges when two carriers have children together and pass it to their offspring.
For each pregnancy of two such carriers, there is a 25% chance that the child will be born with the disease and a 50% chance the child will be a carrier for the gene defect.
Studies conducted since 1979 show that 1 of every 7,500 live births will have some form of galactosemia (Georgia annual Newborn Screening report - 1997). It is also estimated that 1 of every 40 people is a carrier of this defective gene.
Since it is inherited and genetic then it is for life.
Children with classic Galactosemia get very sick - unless lactose is removed from the diet. Most children with galactosemia will develop obvious symptoms in infancy.
Common symptoms include jaundice, feeding difficulties, vomiting, poor weight gain, irritability, lethargy, seizures, cataracts and mental retardation. The liver and spleen are usually enlarged. Serious infections are more common in newborns with galactosemia.
In fact, the infection may be diagnosed before the galactosemia. Adolescent girls with galactosemia will usually have delay in menstruation. Most die during infancy if the Galactosemia is not identified and treated.
Galactosemia is treated by removing lactose from the diet. Lactose is not a necessary part of the diet. Soy formulas are often used as substitutes for babies. When babies begin solid foods, other sources of galactose must be avoided. Removing galactose from the diet may prevent further damage to the kidney, liver, and brain.
Cataracts disappear and growth progresses. Galactosemia is not preventable, but further damage is often preventable by removing galactose from the diet.
Long-term complications such as speech difficulties, learning disabilities and neurological impairment (e.g. tremors, etc), and in girls, ovarian failure are quite significant.
Phenylketonuria
Phenylketonuria (PKU) is a genetic disorder in which the body cannot process part of a protein called phenylalanine (Phe). Phenylalanine is present in almost all foods. It is 1 of the 8 essential amino acids found in foods that contain protein. If the Phenylalanine level gets too high, it can damage the brain and cause severe mental retardation.
Phenylketonuria (PKU) is passed down through families. Both parents must pass on the defective gene in order for a child to have PKU. This is called an autosomal recessive trait. In this disorder there is an enzyme missing called phenylalanine hydroxylase, which is needed to break down phenylalanine.
Accumulation of Phe is harmful to the central nervous system and cause brain damage. If the proteins containing phenylalanine are not avoided, PKU can lead to mental retardation by the end of the first year of life. Older children may develop movement disorders such as athetosis and hyperactivity.
Phenylalanine also plays a role in the body's production of melanin, the pigment responsible for skin and hair color. Children with phenylketonuria often have lighter complexions than brothers or sisters without the disease.
If the condition is untreated or foods containing phenylalanine are not avoided, a "mousy" odor may be detected on the breath and skin and in urine. The unusual odor is due to a build up of phenylalanine substances in the body. Other signs and symptoms include: eczema, microcephaly, tremors, spasticity, jerky movements, unnusual positioning of hands, convulsions, delayed mental and social skills.
PKU is a treatable disease that can be easily detected with a simple blood test at birth. Other diagnostic tests include an enzyme assay to determine if the parents carry the defective gene responsible for PKU. During pregnancy, a chorionic villi sample may be taken to screen the unborn baby for PKU.
Phenylalanine occurs in significant amounts in milk, eggs, and other common foods. The artificial sweetener NutraSweet (aspartame) also contains phenylalanine. Any products containing aspartame should be avoided by children with this disorder.
The best treatment for PKU is a diet of low-protein foods. There are special formulas for newborns. For older children and adults, the diet includes many fruits and vegetables. It also includes some low-protein breads, pastas, and cereals.
Nutritional formulas provide the vitamins and minerals they can't get from their food. A special infant formula called Lofenalac is made for infants with PKU. It can be used throughout life as a protein source that is extremely low in phenylalanine and balanced for the remaining essential amino acids.
Tetrahydrobiopterin (BH4) has been used in mild cases as an experimental treatment.
Taking supplements to replace the long chain fatty acids missing from a standard phenylalanine-free diet may be helpful. Animal studies are in progress on an injectable form of phenylalanine ammonium lyase, an alternate enzyme capable of substituting for phenylalanine hydroxylase.
Babies who get on this special diet soon after they are born develop normally. Many have no symptoms of PKU. It is important that they stay on the diet for the rest of their lives. The outcome is expected to be very good if the diet is closely followed, starting shortly after the child's birth. If treatment is started after 3 years or if the disorder remains untreated, brain damage will occur. (To be continued)
