Phenylketonuria (PKU), which affects between 1/10,000 and 1/15,000 newborns, is caused by the lack of liver enzyme activity needed to break down the amino acid phenylalanine into tyrosine. Phenylalanine is found in the protein of foods. PKU is an autosomal, recessively inherited disorder: both parents have the PKU gene and both pass it on to their baby. A parent who has the PKU gene but not the disease, is a "carrier." When both parents are healthy carriers, there is a one-in-four (25%) chance for an affected child with each pregnancy.

Infants with untreated PKU may appear normal in the first few months of life, but left untreated, mental and motor retardation, microcephaly, poor growth rate, characteristic odor and seizures or tremors will become evident. Additionally, inadequate production of tyrosine (a precursor to pigment formation) results in lighter hair and skin than other family members, as well as eczema. With early detection and proper dietary treatment (use of special foods obtained through metabolic centers and pharmacies), mental retardation is totally preventable and growth and development should be normal. Furthermore, the patient must adhere to a lifelong low-phenylalanine diet and a possible tyrosine supplementation.

Galactosemia (GAL) is a disorder screened for by all 50 states and Washington, D.C. It affects between 1/10,000 and 1/60,000 infants and is a recessively inherited deficiency of the transferase enzyme necessary to break down lactose (milk sugars) and most non-soy commercial infant formulas.

The affected infant may appear normal at birth; however, within a few days to two weeks after initiating milk feedings, the infant develops vomiting, diarrhea, lethargy, jaundice and liver damage. Untreated, the disorder may result in developmental retardation, hepatomegaly, Fanconi's syndrome, growth failure, cataracts and, in severe cases, death. With early detection and strict adherence to a galactose-free diet, diagnosed infants can be expected to achieve satisfactory health. Unfortunately, the body can produce some galactose and, in turn, cause negative effects. Therefore, close developmental monitoring and assessment is recommended.

Congenital hypothyroidism (CH) is another disorder screened for by all states. It affects 1/4,000 babies and results because of total or partial failure of the thyroid gland to develop (aplasia or hypoplasia) or its development in an abnormal location (an ectopic gland). Consequently, there are inadequate amounts of thyroid hormone production, a hormone process important for normal growth and development. Left untreated, congenital deficiency of thyroid hormone results in mental retardation and stunted growth.

Newborns may appear normal for up to three months of age, by which time some brain damage will likely have occurred. Symptoms or clinical signs may include prolonged neonatal jaundice, constipation, lethargy, poor muscle tone, feeding problems, a large tongue, mottled and dry skin, distended abdomen and umbilical hernia.

Maple syrup urine disease (MSUD) is a recessively inherited disorder caused by a deficiency of the branched-chain ketoacid decarboxylase enzyme affecting the metabolism of amino acids, leucine, isoleucine and valine. Affecting between 1/90,000 and 1/200,000 infants, this is a rare disorder associated with progressive neurological damage within a few days of birth. Newborns typically appear normal, but after the first week of life show feeding difficulties, lethargy and failure to thrive. A high-pitched cry, irritability, convulsions, spasticity and central nervous system depression leading to coma are usual. Left untreated, the disease leads to progressive neurological problems, acidosis, seizures, sudden apnea and eventually death at two to four weeks of age.

Biochemically, there is severe metabolic acidosis and frequent hypoglycemia. Plasma leucine starts to rise, usually within 24 hours of birth, and within a few days, ketoacids appear in the urine. Ketoacids possess a characteristic sweet maple syrup odor which gives the disease its name.

Treatment involves strict dietary management and the administration of supplements, along with close developmental monitoring and assessment. Early detection and treatment of MSUD prevents many severe effects of the disease, making normal lives possible.

Tyrosinemia affects approximately 1/324,000 newborns and occurs due to the inability to process the amino acid tyrosine, found in most protein. Chief findings are hepatocellular damage leading to cirrhosis and liver failure, and renal tubular damage resulting in Fanconi syndrome. Frequent symptoms and signs are failure to thrive, hepatomegaly, rickets, thrombocytopenia and a profound clotting disorder, which may resist therapy with parenteral vitamin K. Fatality occurs within the first year of life from liver damage and possible hemorrhaging if the baby is not given a tyrosine-restricted diet.

Homocystinuria affects 1/200,000 newborns. This disorder is caused by an enzyme deficiency that blocks the metabolism of homocysteine into cystathionine. Lack of the enzyme cystathionine synthase causes an accumulation of methionine, homocysteine and various metabolites of homocystine. Clinical manifestations of the disorder vary in degree, type and age of onset. Major clinical features include optical dislocation, mental retardation, osteoporosis and thromboembolism. Death occurs in 50% of homocystinurics by age 20, and in 75% by age 30.

With early detection, strict dietary management and vitamin supplements, growth and development should be normal. Some individuals with cystathionine synthase deficiency respond to large doses of the vitamin pyridoxine (B6). Those not B6-responsive are given a methionine-restricted diet with cystine supplementation.

Congenital adrenal hyperplasia (CAH) affects 1/15,000 newborns. Infants suffer from a deficiency of an adrenal enzyme resulting in limited cortisol production and sometimes limited aldosterone production. After sensing the cortisol deficiency, the pituitary gland overproduces ACTH to demand cortisol production by the adrenal glands. The adrenal glands enlarge but continue to produce inadequate amounts of cortisol. The precursor products of cortisol accumulate and are released into circulation. Without sufficient cortisol and aldosterone, the affected newborn may appear normal, but can quickly develop symptoms including lethargy, vomiting, muscle weakness and dehydration. In severe cases, death may occur within weeks. Infants with milder forms of the disorder are at risk for reproductive and growth complications.

Sickle-cell diseases affect about 1/1300 Georgia infants (about 1/400 infants of African-American descent). They are recessively inherited abnormalities in the structure of hemoglobin. "Sickling" is the term referring to changes in red blood cells causing them to become hard, sticky and crescent-shaped. These malformed red blood cells are easily destroyed and tend to clump in and occlude small blood vessels. As a result, patients may suffer from hemolytic anemia, dactylitis, stroke, pulmonary infarction, splenic sequestration and painful ischemic damage to internal organs.

Affected infants appear normal, but anemia develops in the first few months of life, followed by increased susceptibility to infection, slow growth rates and potential life-threatening splenic sequestrations. By about four years of age, height and weight growth rates slow. Complications of sickle-cell diseases can be minimized with penicillin prophylaxis, appropriate vaccinations and long term management.

Biotinidase deficiency is caused by the lack of an enzyme called biotinidase, which is necessary to liberate biotin from a bound form so that it can be used by the body. A number of other critical enzyme systems rely on sufficient biotin; thus, biotinidase deficiency can lead to seizures, developmental delay, eczema and hearing loss. Affected newborns appear normal at birth but develop symptoms after the first weeks or months of life. Symptoms include hypotonia, ataxia, seizures, developmental delay, hair loss, seborrheic dermatitis, hearing loss and optic nerve atrophy. Metabolic acidosis can result in coma and death. Symptoms can be prevented by early identification and treatment with daily biotin supplements.

Medium-chain acyl-CoA dehydrogenase deficiency (MCAD) is a rare hereditary disease that results from the lack of an enzyme required to convert fat to energy. Complications arise when affected infants have infrequent meals, requiring the body to use its own fat reserves to produce energy. In this instance, life-threatening symptoms and even death can occur. MCAD infants do not exhibit symptoms at birth, but low blood sugar, seizures, brain damage, cardiac arrest and serious illness can occur very quickly in infants who are not fed well. Early detection, monitoring of periods between meal times and a strict diet will allow patients to lead normal lives.