NEWBORN SCREENING
HERITABLE METABOLIC DISORDERS
Biotinidase Deficiency
Biotinidase deficiency is a disorder of biotin recycling. Biotin is a B vitamin which is not synthesized by the body. It is a dietary requirement which bonds with certain apocarboxylases for activation and is vital for gluconeogenesis, fatty acid synthesis and amino acid catabolism. Biotinidase recycles biotin by releasing the bound biotin from short peptide chains or biocytin. In the absence of biotinidase, the biotin is not released or recycled. The lack of biotin causes clinical features of seizures, skin rash, hypotonia, alopecia, conjunctivitis, developmental delay and ataxia.
Screening Method:
Continuous flow spectroscopy method to determine Biotinidase activity.
Treatment:
Dietary supplements of biotin.
Incidence:
1:112,000 births
Congenital Adrenal Hyperplasia (CAH)
In both 21-hydroxylase deficiency and 11b-hydroxlyase deficiency, which together account for about 95% of all Congenital Adrenal Hyperplasia (CAH) cases, 17-α-hydroxyprogesterone (17-OHP) is increased. 17-OHP is a precursor of cortisol. The severity of CAH ranges from “classic, severe” salt-wasting (SW) to “classic, less severe simple-virilizing (SV) to “mild, nonclassic” forms. Symptoms of SW CAH include vomiting, diarrhea, failure to thrive, lethargy, and dehydration. Sodium concentrations will become extremely low and circulatory collapse, shock and death will occur if untreated. Clinical diagnosis in females is possible, due to ambiguous genitalia.
Screening Method:
Measurement of 17-OHP with a time-resolved fluoroimmunoassay. There are rarer forms of CAH which will not be identified through the measurement of 17-OHP.
Treatment:
Medication to replace cortisol and aldosterone. Surgical correction of ambiguous genitalia in females.
Incidence:
1:16,000 births
Congenital Hypothyroidism (CH)
In infants with CH, T4 levels are low, which causes the hypothalamus to stimulate TSH production. However, there is not an increase in T4 to regulate the TSH concentration. Therefore, the TSH continues to be produced and the levels will elevate dramatically. The combined clinical manifestation of low T4 levels and high TSH levels are indicative of CH. Diagnosis and treatment of CH within the first three months of life are crucial to prevent the neurological and mental deficiencies caused by thyroid hormone deprivation.
Screening Method:
Both a fluoroimmunometric assay for measurement of TSH and time-resolved fluoroimmunoassay for measurement of T4.
Treatment:
Medication to replace thyroid hormones.
Incidence:
1:3,500 births
Cystic Fibrosis (CF)
Infants with CF typically have increased levels of IRT, an inactive form of trypsin, due to leakage into circulation after pancreatic injury. Trypsin is produced solely by the pancreas and is necessary for protein uptake during digestion. Symptoms of CF include failure to thrive, chronic respiratory infections and nutritional deficiencies.
Screening Method:
First Tier: Fluoroimmunometric assay measurement of IRT.
Second Tier: DNA mutation analysis for patients with IRT levels in the top 5%.
Treatment:
Nutritional and medical treatment, preferably from a CF Foundation accredited care center.
Incidence:
1:2,500 Caucasian births
Galactosemia
Galactose-1-Phosphate Uridyl Transferase (GALT) is required for the metabolism of galactose. In classical galactosemia, GALT activity is absent or greatly reduced, which in turn causes galactose levels to rise. Symptoms include mental retardation, liver damage, cataracts, and death (which may occur within less than 72 hours after birth). Early detection and treatment is critical to prevent damage to the infant.
Screening Method:
Both the GALT activity and the Total Galactose levels are measured using a continuous flow fluorometry method.
Treatment:
Lactose-free formula to eliminate the source of galactose.
Incidence:
1:50,000 births
Hemoglobinopathies
The hemoglobinopathies can be divided into structural variants or thalassemia syndromes. Structural variants, such as sickle cell, can cause tissue infarction and can be life threatening to an infant due to increased risk of infection. Thalassemias can cause severe anemia, failure to grow, and even death. It is important to the infant’s health that the hemoglobinopathies be identified early so that preventive treatment can be initiated.
Screening Method:
HPLC method to identify Hemoglobin F, A, S, C, D, E, and Bart’s.
Treatment:
Prophylactic penicillin to decrease the risk of infection for infants with Sickle Cell Anemia. Infants with thalassemias can be managed with transfusions and medication.
Incidence:
Sickle Cell Anemia: 1:1,300 infants in the general population and 1:400 of African descent. In West Virginia, two to three infants per year are identified with this disorder.
Phenylketonuria (PKU)
Classical PKU is a metabolic disorder resulting in the deficient production of the liver enzyme phenylalanine hydroxylase. This deficiency prevents the breakdown of phenylalanine, an amino acid present in all foods containing protein. The build-up of phenylalanine prevents the brain from developing and results in mental retardation.
Screening Method:
Phenylalanine levels are measured using a continuous flow fluorometry method.
Treatment:
Special formula that provides nutrients needed for growth but restricts phenylalanine intake.
Incidence:
1:12,000 births
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