Iosef: Screening of the Newborn

Question 1

Screening programs in the USA

Answer 1

US New born screening program
US Genetics programs
Hearing screening
Regional programs
Additional testing

Question 2

T/F: National newborn screening global resource center creates rules for genetic AND non-genetic screening.

Answer 2

True

Question 3

Future challenges

Answer 3

Technological progress

Money (genetic screening is only allowed as secondary confirmation)

Question 4

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.

Answer 4

True

Question 5

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

Answer 5

Guthrie test

Question 6

First level tests

Answer 6

routine blood and urine

Question 7

Second level tests

Answer 7

urine metabolic screen
urine organic acid analysis
plasma amino acid analysis
DNA tests

Question 8

Tertiary studies

Answer 8

Biopsy (“in tissue” enzyme analysis)

Molecular diagnostics

Question 9

Blood sample –> protein extraction –> electrophoresis –> liquid chromatography –>

Answer 9

mass spectrometry

Question 10

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

Answer 10

monogenic trait

Question 11

a single phenotypic trait whose expression is controlled/affected by the action of more than one gene locus.

Answer 11

polygenic trait

Question 12

T/F: mutations have different severity degrees

Answer 12

True

Question 13

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.

Answer 13

leaky; null; silent

Question 14

T/F: Mutations in one gene can cause a cascade effect

Answer 14

True

Question 15

T/F: Many inborn errors are caused by autosomal mutations

Answer 15

True

Question 16

the sum of chemical processes through which food is converted into protoplasm and protoplasm is converted into smaller molecules and energy.

Answer 16

metabolism

Question 17

Inherited deficiency of a key step in a critical metabolic pathway.

Answer 17

inborn error of metabolism

Question 18

What does CF result from? Major clinical consequences?

Answer 18

altered synthesis of a CFTR proteni involved in the transport of chloride ions; abnormally thickened mucous secretions in the lungs and digestive systems

Question 19

Normal CFTR vs mutant CFTR

Answer 19

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

Question 20

Management for inborn errors of metabolism

A —> B XXX C

Answer 20

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)

Question 21

CF is autosomal (blank) mutation. Most have a problem in F508-CFTR

Answer 21

recessive

Question 22

Most abnormal hemoglobin conditions are one of these two

Answer 22

sickle cell anemia

sickle beta thalassemia

Question 23

Mutation in sickle cell disease

Answer 23

glutamate replaced with valine –> Hb is less water soluble and

Question 24

What is the rate of AA who are heterozygous for the sickle cell gene?

Answer 24

1/12

Question 25

People with sickle cell disease may have one particular gene mutation that produces an abnormal version of beta-globin known as (blank)

Answer 25

hemoglobin S

Question 26

hemoglobin gene mutations can also result in an unusually low level of beta-globin - called…

Answer 26

beta thalassemia

Question 27

With congenital hypothyroidism, newborns may appear normal up to three months and if detected early they can have normal growth and development.

Answer 27

True

Question 28

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.

Answer 28

True

Question 29

T/F: administration of T3 as well as T4 may be a better solution for hypothyroidism than T4 alone

Answer 29

True

Question 30

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

Answer 30

galactosemia

Question 31

caused by an enzyme deficiency that blocks the metabolism of homocysteine to cystathionine

Answer 31

homocystinuria

Question 32

major clinical features of homocystinuria

Answer 32

optical dislocation
mental retardation
osteoporosis
thromboembolism

Question 33

a deficiency of the branched-chain ketoacid dehydrogenase enzyme  impaired metabolism of branched-chain amino acids (Leu, Iso-Leu, Val).

Answer 33

Maple Syrup Urine Disease

Question 34

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.

Answer 34

metabolic pathways involved in branch chain amino acid disorders

Question 35

Mild phenotypic form of PKU

Answer 35

hyper-phenyl-alanemia

Question 36

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

Answer 36

Biotinidase deficiency

Question 37

At what level does profound biotin deficiency occur?

Answer 37

when the activity of biotinadase is <10%

Question 38

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

Answer 38

medium chain acyl-CoA DH deficiency

Question 39

A cannot go to B, so it forms organic acids. Together with carnitine, it forms carnitine esters which can be seen in the urine

Answer 39

medium chain acyl-Coa DH deficiency

Question 40

plasma acy-lcarnitines, urine organic acids, urine acy-lglycine

Answer 40

initial tests for medium chain acyl-coa DH deficiency

Question 41

A genetic disorder caused by the misfolding of the protein Fibrillin-1, coded by the gene FBN1

Answer 41

Marfan Syndrome

Question 42

Marfan syndrome is autosomal (blank)

Answer 42

dominant

Question 43

2 major categories of intrauterine growth restriction; which is more common?

Answer 43

symmetrical
asymmetrical;
asymmetrical

Question 44

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

Answer 44

epigenetic responses