Iosef: Screening of the Newborn Flashcards
Screening programs in the USA
US New born screening program US Genetics programs Hearing screening Regional programs Additional testing
T/F: National newborn screening global resource center creates rules for genetic AND non-genetic screening.
True
Future challenges
Technological progress
Money (genetic screening is only allowed as secondary confirmation)
T/F: Although most babies can hear normally, 1 to 3 of every 1,000 babies are born with some degree of hearing loss. Without newborn hearing screening, it is difficult to detect hearing loss in the first months and years of your baby’s life.
True
Helps doctors diagnose some inborn errors of metabolism before they cause permanent damage. The test requires a small sample of blood, usually taken from the heel
Guthrie test
First level tests
routine blood and urine
Second level tests
urine metabolic screen
urine organic acid analysis
plasma amino acid analysis
DNA tests
Tertiary studies
Biopsy (“in tissue” enzyme analysis)
Molecular diagnostics
Blood sample –> protein extraction –> electrophoresis –> liquid chromatography –>
mass spectrometry
a single phenotypic trait whose expression is controlled by the action of a single gene locus. It can be autosomal or “X”- or “Y”- linked, it can also be dominant or recessive
monogenic trait
a single phenotypic trait whose expression is controlled/affected by the action of more than one gene locus.
polygenic trait
T/F: mutations have different severity degrees
True
A (blank) mutations reduces but does not destroy phenotypic expression of wild type. A (blank) mutation results in a completely non-functional version of the wild type enzyme. A (blank) mutation is a change in base sequence that does not alter wild type enzyme function.
leaky; null; silent
T/F: Mutations in one gene can cause a cascade effect
True
T/F: Many inborn errors are caused by autosomal mutations
True
the sum of chemical processes through which food is converted into protoplasm and protoplasm is converted into smaller molecules and energy.
metabolism
Inherited deficiency of a key step in a critical metabolic pathway.
inborn error of metabolism
What does CF result from? Major clinical consequences?
altered synthesis of a CFTR proteni involved in the transport of chloride ions; abnormally thickened mucous secretions in the lungs and digestive systems
Normal CFTR vs mutant CFTR
normal–>ions freely flow in and out of the cells
mutated–>ions cannot flow out of cell due to a blocked channel so creates thick mucous
Management for inborn errors of metabolism
A —> B XXX C
symptomatic supportive therapy
provide C
limit intake and production of B and A
enhance enzyme activity via replacement, stabilization, gene transfer
activate alternative metabolic pathways (D)
CF is autosomal (blank) mutation. Most have a problem in F508-CFTR
recessive
Most abnormal hemoglobin conditions are one of these two
sickle cell anemia
sickle beta thalassemia
Mutation in sickle cell disease
glutamate replaced with valine –> Hb is less water soluble and
What is the rate of AA who are heterozygous for the sickle cell gene?
1/12
People with sickle cell disease may have one particular gene mutation that produces an abnormal version of beta-globin known as (blank)
hemoglobin S
hemoglobin gene mutations can also result in an unusually low level of beta-globin - called…
beta thalassemia
With congenital hypothyroidism, newborns may appear normal up to three months and if detected early they can have normal growth and development.
True
T/F: Congenital hypothyroidism can be caused by mutations in genes that prevent the normal development of the thyroid gland before birth OR mutations in genes that prevent the production of thyroid hormones even through the thyroid gland is present.
True
T/F: administration of T3 as well as T4 may be a better solution for hypothyroidism than T4 alone
True
Deficiency of enzyme that breaks down galactose
Newborns appear normal, but within a few days start vomiting, diarrhea, lethargy, jaundice, liver damage
Untreated –> developmental retardation, growth failure, etc
Management –> early detection and galactose-free diet
galactosemia
caused by an enzyme deficiency that blocks the metabolism of homocysteine to cystathionine
homocystinuria
major clinical features of homocystinuria
optical dislocation
mental retardation
osteoporosis
thromboembolism
a deficiency of the branched-chain ketoacid dehydrogenase enzyme impaired metabolism of branched-chain amino acids (Leu, Iso-Leu, Val).
Maple Syrup Urine Disease
A: maple syrup urine disease; B: dihydrolipoyl dehydrogenase deficiency; C: isovaleric acidemia; D: glutaric acidemia type II; E: multiple carboxylase deficiency; F: HMG-CoA lyase deficiency.
metabolic pathways involved in branch chain amino acid disorders
Mild phenotypic form of PKU
hyper-phenyl-alanemia
caused by the lack of an enzyme called biotinidase, resulting in an inability to liberate biotin from a bound form so that it can be used by the body. Without sufficient biotin, several other critical enzyme systems are unable to function properly. Biotin is used to break down fats, proteins and carbohydrates
Biotinidase deficiency
At what level does profound biotin deficiency occur?
when the activity of biotinadase is <10%
a rare hereditary disease that results from the lack of an enzyme required to convert fat to energy
Missing the acyl-CoA dehydrogenase
Complications when infants have long periods between meals
medium chain acyl-CoA DH deficiency
A cannot go to B, so it forms organic acids. Together with carnitine, it forms carnitine esters which can be seen in the urine
medium chain acyl-Coa DH deficiency
plasma acy-lcarnitines, urine organic acids, urine acy-lglycine
initial tests for medium chain acyl-coa DH deficiency
A genetic disorder caused by the misfolding of the protein Fibrillin-1, coded by the gene FBN1
Marfan Syndrome
Marfan syndrome is autosomal (blank)
dominant
2 major categories of intrauterine growth restriction; which is more common?
symmetrical
asymmetrical;
asymmetrical
Intrauterine growth restriction triggers (blank) in the fetus that are otherwise activates in times of chronic food shortage. If the offspring actually develops in an environment rich in food, it may be more prone to metabolic disorders
epigenetic responses
