Newborn Metabolic Screening

Newborn metabolic screening is the practice of testing every newborn for certain harmful or potentially fatal disorders that are not otherwise apparent at birth. Newborn screening tests take place before the newborn leaves the hospital. Babies are tested to identify serious or life-threatening (and for the most part preventable or treatable) diseases before symptoms begin. These diseases are usually rare. However, if they are not accurately diagnosed and treated, they can cause mental retardation, severe illness, and premature death in newborns. Many of these are metabolic disorders, often called “inborn errors of metabolism.” Other disorders that may be detected through screening are endocrine or hematologic. In most states, this testing is mandatory. More than 98% of all children born in the United States are tested for these disorders.


Within 48 hours of a child’s birth, a sample of blood is obtained from a “heel stick,” and the blood is analyzed. The sample, called a “blood spot,” is tested at a reference laboratory. It is generally recommended that the sample be taken after the first 24 hours of life. Some tests, such as the one for Phenylketonuria (PKU), may not be as sensitive until the newborn has ingested an ample amount of the amino acid phenylalanine, which is a constituent of both human and cow’s milk, and after the postnatal thyroid surge has subsided. This is generally after about 2 days.


With the use of Tandem mass spectrometry (tandem MS), multiple blood tests can be performed quickly and efficiently. When directed to newborn blood screening, the use of these specialized instruments can detect abnormally elevated proteins associated with certain metabolic disorders. They are capable of screening for more than 20 inherited metabolic disorders with a single test in only a few minutes. Tandem MS is very accurate and can measure very small amounts of similar material with excellent precision. For example, PKU (see below) tandem MS has been shown to reduce the false positive rate (false alarms) for this disorder more than tenfold compared to the best alternative method available. Below is a list of the disorders that most Newborn Metabolic Screen programs would include:


Phenylketonuria (PKU): An inherited disease, PKU is characterized by deficiency of the enzyme phenylalanine hydroxylase, which converts phenylalanine to tyrosine. Phenylalanine is an essential amino acid necessary for growth; however, any excess must be degraded by conversion to tyrosine. An infant with PKU lacks the ability to make this necessary conversion. Thus phenylalanine accumulates in the body and spills over into the urine. If the amount of phenylalanine is not restricted in infants with PKU, progressive mental retardation results. A PKU diagnosed child will follow a died of low phenylalanine until adulthood. Depending on the condition, the low phenylalanine diet may be followed during adult life. (Incidence: 1 in 10,000 to 25,000).

Congenital Hypothyroidism: Affected babies without treatment experience retarded growth and brain development. When this disease is diagnosed early, thyroid hormone dosages will help to maintain normal growth and brain development of the baby. (Incidence: 1 in 4000).

Galactosemia: Is the condition in which human body cannot convert galactose (a sugar of milk) into glucose due to a deficiency of the Lactase enzyme. Galactosemia lead to high galactose levels. While human body benefits from glucose, high levels of galactose damage several types of vital cells and lead to harmful conditions including blindness, mental retardation, or death as worst case. For this reason, early diagnosis of Galactosemia can save lives since an intervention of a milk and dairy products free diet can be followed in order to prevent high galactase levels.(Incidence: 1 in 60,000 to 80,000.) There are also several less severe forms of galactosemia that may be detected by newborn screening. These may not require any intervention.

Sickle Cell Anemia: Sickle cell anemia is a genetic blood disorder which occurs when the newborn body fails to produce Adult Hemoglobin (Hemoglobin A) and produces an abnormal Hemoglobin Variant known as Hemoglobin S. Hemoglobin S causes the red blood cells to take the shape of a sickle. While normal RBCs have a spherical shape that makes it easy to circulate all over the circulatory system, the abnormal shape of sickle cells makes cause them to accumulate in the blood vessels leading to pain episodes and damage to vital organs including the lungs which may lead to death. Sickle cell anemia is usually accompanied with dangerous bacterial infections in young children. (Incidence; For African Americans: 1 in 500 births. For Hispanic Americans 1 in 1000 to 1400 births.)

Biotinidase Deficiency: Biotinidase Deficiency is the genetic condition of having low Biotinidase levels. Biotinidase is an enzyme which recycles Biotin. Biotin is a type of Vitamin B, Biotin is is some times known as Vitamin H. Human body cannot produce Biotin. However, the vitamin is important to properly processing proteins, fats, and carbohydrates. When Biotin is not recycled, as a result of Biotinidase Deficiency, Biotin Levels are increased and the nutrition processing is inhibited causing lack of coordination and poor muscle control, behavioral disorders and mental retardation, seizures, coma, or death. However, taking small amounts of Biotin will help nutrition to be processed properly and prevent harmful consequences from occurring. If Biotinidase Deficiency is discovered  early, intervention with biotin supplement will be more effective in growing a healthy child. (Incidence: 1 in 126,000.)


Congenital Adrenal Hyperplasia: This is a group of disorders caused by deficiencies of adrenal hormones. Adrenal hormones are important for sexual development. Deficiencies of adrenal hormones leads to abnormal sex characteristics and may cause abnormal development of the genitals. Deficiencies of adrenal hormones can also lead to death. taking hormone supplementation, however, helps avoiding the complications of Congenital Adrenal Hyperplasia and lead to normal development of the sexual characteristics and organs. This makes it important to discover the condition as early as possible using Newborn Screening before abnormalities take place. (Incidence: 1 in 12,000.)

Maple Syrup Urine Disease (MSUD): MSUD is condition caused by a deficiency of an enzyme complex that processes Branched-chain Amino Acids (Leucine, Isoleucine, and Valine). Since these amino acids are not processed, their levels increase in the blood and urine as well causing the baby urine to have a sweet odor which smells like Maple Syrup. Inability to process Branched-chain Amino Acids (BCAA) cause them to build up in the body leading to development and growth delay, mental retardation, physical disabilities and may be death. Branched-chain Amino Acids are found in high protein foods, specially in animal protein sources including meat, eggs, milk, and diary products.

There are several types of Maple Syrup Urine Disease, the most severe type is the one which appears after birth, which makes early diagnosis of MSUD is even more pressing matter. Babies with MSUD usually lack good appetite. A diet free of high-protein nutrition will help avoiding the complications caused by inability to process BCAA. (Incidence: 1 in 180,000.)

Homocystinuria: Homocystinuria is an inherited metabolic disorder caused by cystathionine β-synthase deficiency. Cystathionine β-synthase (CBS) is an enzyme that catalyzes the conversion of homocysteine and methionine into cysteine. As a result, deficiency of CBS (Homocystinuria) will cause high homocysteine and metionine levels in the blood and urine and these high levels will lead to mutilsystemic disorder of the connective tissue, muscles, and cardiovascular system. They can also cause dislocated lenses of the eyes, mental retardation, and skeletal abnormalities. If discovered early, these problems can be avoided by in less than 50% of the patients by giving them high dosages of vitamin B6. Those who don’t respond to vitamin B6 treatment can be treated with trimethylglycine and have a low metionine diet by avoiding certain foods including eggs, fish, meat, and sesame seads. Since the body fails producing adequate amounts of cysteine, cysteine can be added to the diet to reduce oxidative stress. (Incidence: 1 in 50,000 to 150,000.)

Tyrosinemia: This is a metabolic disorder in which amino acid tyrosine is not broken down effectively. High Levels of Tyrosine may lead to mental retardation, speech difficulties, liver disease, or death due to liver failure. All these consequences may be avoided is Tyrosinemia is discovered and treated early.

There are three types of Tyrosinemia; Tyrosinemia treatment vary depending on the type. The most effective treatment of Type I Tyrosinemia is partial or full liver transplant. A diet of low protein intake can help managing Tyrosinemia as well.

Cystic Fibrosis: A genetic disorder which affects the cells of the lungs and gastrointestinal tract causing them to release thick mucus (Cyst). The cyst which exists in the lungs causes chronic respiratory disease. Cystic Fibrosis can also cause digestion problems since the thick mucus affect the digestive fluids which breakdown the food causing growth problems and damage to the Pancreas. CF can cause infertility as well. Antibiotics are used to manage the condition and prevent severe lung infections. Lung Transplantation can be necessary as CF advances. Cystic Fibrosis is common among Caucasians of Central and Northern Europe (Incidence: 1 in 2000 white babies.)


Toxoplasmosis: This is a parasitic disease that is transmitted to human mainly from cats and sometimes from handing raw meat or eating undercooked infected meat. Mothers can transmit the infection to the fetus and the condition can be detected using new born screening. The infection can affect the nervous and muscle tissues and cause damage to the eyes and the brain. (Incidence: 1 in 1000.)



Depending on the condition and the mother’s  and the newborn family’s history with diseases, the newborn screening and can be also used to detect other diseases than the ones listed previously. Newborn screening can include testing for Duchenne’s Muscular Dystrophy, Human Immune Deficiency Virus (HIV) infection, and Neuroblastoma. Hematologic disorders, such as Glucose-6-phosphate Dehydrogenase (G6PD) deficiency and Thalassemia, can also be identified.


Most, but not all, states require newborns’ hearing to be screened before they are discharged from the hospital. The hearing test involves placing a tiny earphone in the baby’s ear and measuring his or her response to sound. A child develops critical speaking and language skills in the first few years of life, and if a hearing loss is discovered early, developmental effects on language skills can be avoided.




Causes of Newborn Metabolic Screening False Results

  • Premature infants may have false-positive results of any of the above diseases because of delayed development of liver enzymes.
  • Infants tested before 24 hours of age may have false-negative results.
  • Feeding problems, Vomiting for example, may cause false-negative results.




Benefits of Performing Newborn Metabolic Screening

Newborn Metabolic Screening is very helpful when it comes to early diagnosis of Metabolic Diseases, Endocrine Diseases, and Hematologic Diseases. The detection of these disorders before they become clinically apparent may allow opportunities for treatment before there are significant mental or physical harm to the newborn.