Disorder Descriptions
The Alabama Bureau of Clinical Laboratories currently screens for thirty-five core conditions included in the Advisory Committee on Heritable Disorders in Newborns and Children, Recommended Uniform Screening Panel. Below is a list of core disorder descriptions along with a link to the American College of Medical Genetics and Genomics (ACMG) ACT Sheets to help inform clinical decision making.
Table of Contents
1. 3-Methylcrotonyl-CoA Carboxylase Deficiency (3MCC)
2. Argininosuccinic Acidemia (ASA)
3. Beta-Ketothiolase Deficiency (BKT)
4. Biotinidase Deficiency (BIOT)
5. Carnitine Uptake Defect (CUD)
7. Classical Galactosemia (GALT)
8. Congenital Adrenal Hyperplasia (CAH)
9. Congenital Hypothyroidism (CH)
10. Critical Congenital Heart Disease (CCHD)
12. Glutaric Acidemia Type I (GA1)
13. Hb S/Beta-Thalassemia (HBSA)
17. Hydroxymethylglutaric Aciduria or HMG-CoA Lyase Deficiency or 3-OH 3-CH3 Glutaric Aciduria (HMG)
19. Long-Chain 3-OH Acyl-CoA Dehydrogenase Deficiency (LCHAD)
20. Maple Syrup Urine Disease (MSUD)
21. Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCAD)
22. Methylmalonic Acidemia CblA and CblB Forms (CBLAB)
23. Methylmalonic Acidemia Due to Mutase Deficiency (MUT)
24. Mucopolysaccharidosis Type I (MPS I)
25. Multiple Carboxylase Deficiency (MCD)
27. Pompe disease
29. Severe Combined Immunodeficiency (SCID)
31. Spinal Muscular Atrophy (SMA)
32. Trifunctional Protein Deficiency (TFP)
34. Very Long-Chain Acyl-CoA Dehydrogenase Deficiency (VLCAD)
35. X-linked Adrenoleukodystrophy (X-ALD)
1. 3-Methylcrotonyl-CoA Carboxylase Deficiency (3MCC)
Incidence: Greater than 1 in 75,000 live births
3MCC ACMG ACT Sheet
This defect in processing the amino acid leucine can lead to brain damage, seizures, liver failure, and death in infancy, or no symptoms at all into adulthood. Symptoms often develop following a childhood illness. Treatment with a low-protein diet and, in some cases, nutritional supplements may be helpful. (An abnormal result by newborn screening could be related to abnormal metabolites in the mother, but not the baby. This will be clarified by further diagnostic testing of the infant.) For more information, view the complete description.
2. Argininosuccinic Acidemia (ASA)
Incidence: Less than 1 in 100,000 live births
ASA ACMG ACT Sheet
Symptoms most commonly begin in the first few days of life, with the build-up of argininosuccinic acid, and ultimately ammonia resulting in brain swelling, coma, and sometimes, death. Survivors often suffer permanent neurological damage. Other affected children may develop symptoms later in infancy or childhood. Early diagnosis and treatment can be lifesaving. However, in spite of treatment, affected individuals remain susceptible to episodes of ammonia build-up, and most have some degree of brain damage. Treatment consists of a low-protein diet, avoiding fasting, medications to prevent ammonia build-up, nutritional supplements, and in some cases, liver transplant. For more information, visit the Genetics Home Reference website.
3. Beta-Ketothiolase Deficiency (BKD)
Incidence: Less than 1 in 100,000 live births
BKD ACMG ACT Sheet
Periodic episodes of acid build-up, often triggered by some childhood illness, can progress to coma, brain damage, and death. These serious consequences are most often seen in infants. With early diagnosis and prompt intravenous treatment to keep blood sugar levels up and blood acid levels down during an illness, children can develop normally. Parents must be alert to early signs of illness. Additional treatments may vary but can include avoidance of protein-rich diets and long-term treatment with bicarbonate. For more information, view the complete description.
4. Biotinidase Deficiency (BIOT)
Incidence: Greater than 1 in 75,000 live births
Biotinidase ACMG ACT Sheet
Biotinidase is the enzyme that recycles the vitamin, biotin. An inherited deficiency of this enzyme may cause serious complications, including frequent infections, uncoordinated movement, hearing loss, seizures, and mental retardation. Undiagnosed and untreated, the deficiency can lead to coma and death. If the condition is detected soon after birth, these problems can be completely prevented with daily oral doses of biotin. For more information, visit the Genetics Home Reference website.
5. Carnitine Uptake Defect (CUD)
Incidence: Less than 1 in 100,000 live births
CUD ACMG ACT Sheet
Due to a missing transporter, cells cannot bring in carnitine from the blood. Carnitine is needed for the transfer of fatty acids across the membranes of the mitochondria (cellular organelles that produce energy for the cell). Symptoms include episodes of hypoglycemia (low blood sugar) and sudden unexpected death in infancy. Older children may present with progressive heart failure. Early diagnosis and treatment with carnitine permits normal development. For more information, view the complete description.
6. Citrullinemia (CIT)
Incidence: Less than 1 in 100,000 live births
Citrullinemia ACMG ACT Sheet
A build-up in the body of citrulline and ultimately ammonia can begin during the newborn period or later in infancy. Without treatment, seizures, coma, brain damage, and death can result. With early diagnosis and treatment, normal development is possible. Treatment includes a low-protein diet, medications to rid the body of amino groups to prevent ammonia build-up, and nutritional supplements. For more information, view the complete description.
7. Classical Galactosemia (GALT)
Incidence: Greater than 1 in 50,000 live births
Galactosemia ACMG ACT Sheet
Affected babies are missing the liver enzyme needed to convert galactose, a major sugar from the breakdown of lactose in milk, into glucose, another simple sugar that the body can use. Galactose then accumulates in and damages vital organs, leading to blindness, severe mental retardation, infection, and death. Milk and other dairy products must be eliminated from the baby's diet for life. Though treatment dramatically improves the outlook for affected infants, there is still some risk of developmental delays. For more information, visit the Genetics Home Reference website.
8. Congenital Adrenal Hyperplasia (CAH)
Incidence: Greater than 1 in 25,000 live births
CAH ACMG ACT Sheet
CAH refers to a set of inherited disorders resulting from defects in the synthesis of hormones produced by the adrenal gland. In female infants, CAH sometimes results in masculinization of the genitals. Certain severe forms of CAH cause life-threatening salt loss from the body if undetected and untreated. Treatment includes salt replacement and hormone replacement. For more information, view the complete description.
9. Congenital Hypothyroidism (CH)
Incidence: Greater than 1 in 5,000 live births
CH ACMG ACT Sheet
This thyroid hormone deficiency severely retards both growth and brain development. If detected soon after birth, the condition can be treated simply with oral doses of thyroid hormone to permit normal development. For more information, view the complete description.
10. Critical Congenital Heart Disease (CCHD)
Incidence: 11.6 per 10,000 live births
Critical Congenital Heart Disease is classified as seven specific heart defects: hypoplastic left heart syndrome, pulmonary atresia (with intact septum), Tetralogy of Fallot, total anomalous pulmonary venous return, transposition of the great arteries, tricuspid atresia, and truncus arteriosus. These defects create a problem with the heart's structure and/or function which is present at birth. In the United States, about 4800 babies born every year have CCHDs. These babies are at risk for having serious complications within the first few days or weeks of life and often require emergency care. Pulse oximetry newborn screening per the state screening algorithm may identify some infants with a CCHD before they show signs. Once identified, babies with a CCHD can be seen by a pediatric cardiologist and can receive specialized care and treatment that could prevent death or disability. For more information, view the complete description.
11. Cystic Fibrosis (CF)
Incidence: Greater than 1 in 5,000 live births
CF 1 Variant ACMG ACT Sheet
CF 2 Variant ACMG ACT Sheet
CF High IRT ACMG ACT Sheet
Cystic fibrosis is one of the most common inherited disorders in the U.S. Abnormalities in the cystic fibrosis protein result in lung and digestive problems, and death at an average age of 30-35 years. Studies suggest that early diagnosis and treatment improve the growth of babies and children with CF. Treatment varies depending on the severity of symptoms but may include a high-calorie diet supplemented with vitamins and medications to improve digestion, respiratory therapy to help clear mucus from the lungs, and medications to improve breathing and prevent lung infections. For more information, view the complete description.
12. Glutaric Acidemia Type I (GA1)
Incidence: Greater than 1 in 75,000 live births
GA ACMG ACT Sheet
Babies may develop normally for up to 18 months until something affects a child's health, such as a mild viral illness, which may trigger the onset of symptoms. Without prompt treatment, this can lead to brain damage, seizures, low muscle tone, cerebral palsy-like symptoms, and death within the first decade of life. Some affected babies also are born with an enlarged head (macrocephaly). Treatment can vary but may include dietary protein restriction and supplementation with a nutrient called L-carnitine. With early diagnosis and prompt treatment of illness and fever, brain damage may be prevented. For more information, view the complete description.
13. Hb S/Beta-Thalassemia (HBSA)
Incidence: Greater than 1 in 50,000 live births
Hemoglobin FSA ACMG ACT Sheet
In this form of sickle cell anemia, the child inherits one sickle cell gene and one gene for beta thalassemia, another inherited anemia. Symptoms are often milder than for Hb SS, though the severity varies among affected children. Routine treatment with penicillin may not be recommended for all affected children. For more information, visit the Sickle Cell Disease Association of America.
14. Hb S/C Disease (HbSC)
Incidence: Greater than 1 in 25,000 live births
Hemoglobin FSC ACMG ACT Sheet
Another form of sickle cell disease is in which the child inherits one sickle cell gene and one gene for another abnormal type of hemoglobin called HbC. As with Hb S/Th, this form is often milder than the Hb SS and routine penicillin treatment may not be recommended. For more information, visit the Sickle Cell Disease Association of America.
15. Hearing Loss (HEAR)
Incidence: Greater than 1 in 5,000 live births; up to 3-4 per 1,000 newborns
Congenital Hearing Loss ACMG ACT Sheet
Without early testing, most babies with hearing loss are not diagnosed until two or three years of age. By this time, they often have delayed speech and language development. Early diagnosis allows the use of hearing aids by six months of age, helping prevent serious speech and language problems. For more information, visit the Centers for Disease Control and Prevention's Early Hearing Detection and Intervention (EHDI) Program.
16. Homocystinuria
Incidence: Less than 1 in 100,000 live births
Homocystinuria ACMG ACT Sheet
Individuals with this disorder lack an enzyme responsible for converting the amino acid homocysteine into cystathionine, which is needed for normal brain development. If undetected and untreated, homocystinuria leads to mental retardation, eye problems, skeletal abnormalities, and stroke. Treatment consists of a special diet, one or more vitamins (B6 or B12), and other supplements (betaine). For more information, visit the Genetics Home Reference website.
17. Hydroxymethylglutaric Aciduria, or HMG-CoA Lyase Deficiency, or 3-OH 3-CH3 Glutaric Aciduria (HMG)
Incidence: Less than 1 in 100,000 live births
HMG ACMG ACT Sheet
An inability to process the amino acid leucine leads to low blood sugar and accumulation of several organic acids, especially following illness or fasting. Without treatment, the disorder can lead to brain damage, mental retardation, coma, and death. Avoiding fasting and following a diet low in protein and fat and high in carbohydrates can lead to normal development. For more information, view the complete description.
18. Isovaleric Acidemia (IVA)
Incidence: Less than 1 in 100,000 live births
IVA ACMG ACT Sheet
This disorder is caused by an inability to process the amino acid leucine. The newborn form of the disorder often results in coma, permanent neurological damage, and death. In other cases, symptoms develop later in infancy and childhood, frequently following an infectious illness. With early diagnosis and treatment, most children have normal development. Treatment includes a low-protein diet and nutritional supplements. For more information, view the complete description.
19. Long-Chain 3-OH Acyl-CoA Dehydrogenase Deficiency (LCHAD)
Incidence: Greater than 1 in 75,000 live births
LCHAD ACMG ACT Sheet
Symptoms can begin soon after birth, resulting in heart, lung, or liver failure, and death. In other cases, symptoms such as low muscle tone, developmental delay, heart, lung, or liver failure may develop later in infancy or childhood, most likely following an illness. Early diagnosis and treatment effectively prevent life-threatening events, though some children may still develop symptoms. Treatment includes a high-carbohydrate - low-fat diet, nutritional supplements, and avoidance of fasting. Women who are pregnant with fetuses with LCHAD are at increased risk of developing acute fatty liver of pregnancy and other pregnancy complications. For more information, view the complete description.
20. Maple Syrup Urine Disease (MSUD)
Incidence: Less than 1 in 100,000 live births
MSUD ACMG ACT Sheet
This inborn error of metabolism can be lethal if unrecognized and untreated. There is a wide spectrum of clinical presentations, from mild to severe. Affected babies appear normal at birth, but they soon begin to have neurological symptoms. The disorder gets its name from the fact that the urine smells like maple syrup. Without dietary treatment, severely affected babies do not survive the first month; even those who do receive treatment may have irreversible mental retardation. Rapid diagnosis and treatment are major factors in survival and outcome. Treatment consists of a special low-protein diet, which will vary depending on severity of symptoms, and sometimes, supplementation with a vitamin, thiamin. The diet must be continued indefinitely with frequent monitoring. For more information, view the complete description.
21. Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCAD)
Incidence: Greater than 1 in 25,000 live births
MCAD ACMG ACT Sheet
Seemingly well infants and children can suddenly develop seizures (caused by low blood sugar), liver failure, coma, and death. Identifying affected children before they become ill is vital to preventing a crisis and averting these consequences. Treatment includes avoidance of fasting and nutritional supplements. For more information, view the complete description.
22. Methylmalonic Acidemia CblA and CblB Forms (CBLAB)
Incidence: Less than 1 in 100,000 live births
MMA ACMG ACT Sheet
This inherited defect of vitamin metabolism can lead to build-up of acids in the blood and result in brain damage, seizures, paralysis, coma, and death. Symptoms can begin as early as the first week of life, though a minority of affected individuals remains symptom-free. Treatment with vitamin B12 injections and a low-protein diet often prevents serious problems. For more information, view the complete description.
23. Methylmalonic Acidemia Due to Mutase Deficiency (MUT)
Incidence: Greater than 1 in 75,000 live births
MMA ACMG ACT Sheet
A defect in the processing of four essential amino acids and other substances results in illness in the first week of life. Though severity of symptoms varies greatly, death during the first month of life and brain damage in survivors is common. Treatment includes a low-protein diet, vitamin B12 injections, and nutritional supplements. Some children die during the first year of life or develop brain damage despite nutritional intervention. For more information, visit the Genetics Home Reference website.
24. Mucopolysaccharidosis Type I (MPS I)
Incidence: 1 in 100,000 (severe type) and 1 in 500,000 (attenuated type) live births
MPS I ACMG ACT Sheet
A rare genetic disorder that affects many parts of the body and is caused by an accumulation of lysosomal enzymes. There is a severe form (Hurler syndrome) and an attenuated (meaning reduced) form of the disorder based on age of onset, severity of symptoms, rate of disease, and whether there is early involvement of the brain. Children with MPS I often have no signs or symptoms at birth. Treatment may include enzyme replacement therapy or stem cell transplant. For more information, visit the Genetics Home Reference website.
25. Multiple Carboxylase Deficiency (MCD)
Incidence: Less than 1 in 100,000 live births
MCD ACMG ACT Sheet
This disorder is caused by a defect of an enzyme required to activate several biotin-dependent enzymes. Without these enzymes, lactic acid and other organic acids build up in the body. Without treatment, brain damage, coma, and death can result. Symptoms usually begin between birth and 15 months of age, and may include skin rashes and hair loss. Early diagnosis and treatment with biotin allows normal growth and development. For more information, visit the Genetics Home Reference website.
26. Phenylketonuria (PKU)
Incidence: Greater than 1 in 25,000 live births
PKU ACMG ACT Sheet
Affected individuals have an inability to properly process the essential amino acid phenylalanine, which then accumulates and damages the brain. PKU can result in severe mental retardation unless detected soon after birth and treated with a special formula. Affected individuals must be kept on a low-phenylalanine diet at least throughout childhood, adolescence, and for females during pregnancy. For more information, view the complete description.
27. Pompe Disease
Incidence: 1 in 40,000 ilve births
Pompe ACMG ACT Sheet
An inherited disorder caused by a buildup of a sugar called glycogen. There are three types of Pompe disease, which differ in severity and the age of onset. These types are known as classic infantile onset, non-classic infantile-onset, and late-onset. Infants with the severe form of the disorder typically experience msucle weakness, poor muscle tone, an enlarged liver, and heart defects. Treatment requires the coordinated efforts of a team of specialists and may include enzyme replacement therapy and other supportive therapies. For more information, visit the Genetics Home Reference website.
28. Propionic Acidemia (PROP)
Incidence: Greater than 1 in 75,000 live births
PA ACMG ACT Sheet
This defect in the processing of four essential amino acids leads to illness during the newborn period. Without treatment, brain damage, coma and death can result. Even with treatment, including a low-protein diet and nutritional supplements, some affected children suffer from developmental delays, seizures, abnormal muscle tone, frequent infections, and heart problems. For more information, view the complete description.
29. Severe Combined Immunodeficiency (SCID)
Incidence: Greater than 1 in 50,000 live births
SCID ACMG ACT Sheet
A genetic disorder that results in a failure to develop T-cells and inability to make protective antibodies. Most newborns with SCID appear healthy at first because the mother's immune system protects them from infections for the first few weeks of life. However, without treatment, even common infections can be life threatening. The most effective treatment for SCID is a bone marrow transplant. This treatment can be done soon after birth and has a high success rate when done in the first few months of life. A diagnostic evaluation by a pediatric immunologist will determine what kind of treatment is required.
30. Sickle Cell Anemia (HBSS)
Incidence: Greater than 1 in 5,000 live births; higher incidence among African-Americans (1 in 400)
Hemoglobin FS ACMG ACT Sheet
A blood disease that can cause severe pain, damage to the vital organs, stroke, and sometimes death in childhood. Young children with sickle cell anemia are especially prone to dangerous bacterial infections, such as pneumonia and meningitis. Vigilant medical care and treatment with penicillin, beginning in infancy, can dramatically reduce the risk of these adverse effects and the deaths that can result from them. Affected babies should receive all regular childhood vaccinations (including hemophilus influenza B and pneumococcal vaccines) to help prevent serious bacterial infections. Additional treatments may vary according to severity of symptoms, but may include intermittent pain medications and regular blood transfusions. For more information, visit Sickle Cell Disease Association of America.
31. Spinal Muscular Atrophy (SMA)
Incidence: 1 in 10,000
SMA ACMG ACT Sheet
An inherited condition that affects nerve cells (motor neurons) of the spinal cord and brain stem. These motor neurons control certain muscles of the body. Over time, as more motor neurons are lost, the muscles get weaker and activities such as crawling, walking, and breathing become more difficult. For more information, view the complete description.
32. Trifunctional Protein Deficiency (TFP)
Incidence: Less than 1 in 100,000
TFP ACMG ACT Sheet
A seemingly healthy infant can die suddenly of what appears to be sudden infant death syndrome. Other infants may develop low muscle tone, seizures, heart failure, and coma often following an illness. Treatment is based on strict avoidance of fasting, a low-fat diet and nutritional supplements. For more information, view the complete description.
33. Tyrosinemia Type I (TYR1)
Incidence: Less than 1 in 100,000 live births
Tyrosinemia ACMG ACT Sheet
Due to absence of an enzyme, byproducts of the amino acid tyrosine, particularly a very toxic compound called succinylacetone, build up in the liver. Without treatment, symptoms generally begin in the first few weeks or months of life and progress to liver or kidney failure, nerve damage and death. Drug treatment, sometimes along with a low-protein diet, is very effective in preventing liver and kidney damage. For more information, view the complete description.
34. Very Long-Chain Acyl-CoA Dehydrogenase Deficiency (VLCAD)
Incidence: Greater than 1 in 75,000 live births
VLCAD ACMG ACT Sheet
Symptoms can first appear at any age from the newborn period through adulthood, but tend to be most severe in infants. Without treatment, affected infants often develop heart and liver failure and die during the first year of life. Treatment includes a high-carbohydrate - low-fat diet, nutritional supplements, avoidance of fasting, and prolonged exercise. For more information, view the complete description.
35. X-linked Adrenoleukodystrophy (X-ALD)
Incidence: 3 in 100,000 live births
X-ALD ACMG ACT Sheet
X-ALD is a rare genetic disorder caused by a change in a single gene that affects males. X-ALD happens when certain fats cannot be broken down in the body. The fats bulid up and cause health problems including damage to the nervous system and adrenal glands. Possible treatment for X-ALD include supportive therapies (such as physical therapy), steriod treatment, and stem cell transplants. For more information, view the complete description.
Disclaimer: The purpose of newborn screening is to identify infants at risk and in need of more definitive testing. As with any laboratory test, both false negative and false positive results are possible. Screening results are insufficient information on which to base diagnosis or treatment.
Page last updated: November 18, 2024
