Genetics- Metabolic Disorders of the newborn- Dr. Adkison

Question 1

where are Housekeeping genes expressed?

Answer 1

in all cell types. expressed all the time and regulated

Question 2

giving a recombinant enzyme, glucocerebrosidase, for a pt w/ Type 1 Gauchers is an example of what method of treating inherited enzyme mutation?

Answer 2

replacement of mutant protein

Question 3

what are the essential amino Acids?

Answer 3

PVT. TIM HALL

phenylalanine, valine, tryptophan, threonine, isoleucine, methionine, histidine, arginine, leucine, lysine

Question 4

increased amounts of what in urine causes a mousey odor of the urine? what disorder is this seen in?

Answer 4

Phenylalanine- in Phenylketonuria

Question 5

a kid presents with light har, bluish eyes, microcephaly, likes to sit in a unusual “tailor” position and has an IQ of 29. what disorder is this classic presentation of?

Answer 5

Phenylketonuria

Question 6

Phenylketonuria is a mutation in what enzyme?

Answer 6

phenylalanine hydroxylase

Question 7

Clinical expectations with PKU type 1?

Answer 7

elevated phenylalanine, reduced or normal tyrosine, normal at birth, toxic to infant neurological tissue. damage occurs after birth (0-6 months)

Question 8

what is the Guthrie test? whats a positive outcome?

Answer 8

bacterial inhibition assay that tests for PKU. >4mg/100dL then suspect PKU

Question 9

what do PKU patients have to limit their intake in their diet?

Answer 9

Phenylalanine

Question 10

what else causes a positive Guthrie test?

Answer 10

high PHE, High TYR (low birth weight, protein formula, vit. C deficiency) liver disease, Galactosemia

Question 11

If positive Guthrie test reveals elevated PHE. what should you perform next? what result is a typical PKU patient?

Answer 11

blood test. >15mg/100ml PHE and <5 mg/100ml TYR

Question 12

Major clinical finding in type 2 hyperphenylalanine?

Answer 12

abnormal response to diet. progressive detioration of brain fxn leading to death

Question 13

what is deficient in TYPE 2 hyperphenylalanine? what is it required for?

Answer 13

Dihydropteridine Reductase

BH4 synthesis, required for tyrosine and tryptophan pathways –> neurotransmitters

Question 14

elevated PHE
reduced or normal TYR 
reduced BH4
elevated BH2 
dopamine, serotonin levels low 
what disorder has this clinical presentation?

Answer 14

type 2 hyperphenylalanemia

Question 15

elevated neopterin 
reduced sepiapterin 
reduced BH4
reduced BH2 
elevated PHE

Answer 15

TYPE 3 hyperphenylalanemia

Question 16

offspring with mental retardation and microcephaly due to maternal PKU, is due to what mechanism?

Answer 16

PHE crosses the placenta and Phenylalanine hydroxylase from fetal liver is unable to convert to tyrosine

Question 17

what inheritence is PKU?

Answer 17

autosomal recessive

Question 18

what is the mildest form of phenylalanine hydroxylase deficiency?

Answer 18

non- PKU HyperPhenylAlanine

Question 19

a child presents with dark urine and increased levels of homogentistic acid?

Answer 19

Alkaptonuria

Question 20

Alkaptonuria is a deficiency in what enzyme?

Answer 20

homogentisic acid oxidase

Question 21

what is a deficiency in tyrosinase?

Answer 21

Albinism. can’t form melanins from tyrosine

Question 22

what are the activities of tyrosinease in Type 1A classic albinism? and Type 1B classic albinism?

Answer 22

1A- tyrosinase activity is negative

1B- activity is reduced

Question 23

what is the most common form of albinism in the world? what is the activity of tyrosinase?

Answer 23

albinism type 2

activity is positive

Question 24

what is present in type 2 to differentiate it from type 1B?

Answer 24

presence of pigmented nevi. (difficult to ID in blacks.) hair will be yellow or very light colored

Question 25

what is the deficient enzyme in Tyrosinemia?

Answer 25

p-hydroxyphenypyruvic oxidase

Question 26

what is secreted in the urine in Tyrosinemia? whats high in newborns blood?

Answer 26

p-hydroxyphenylpyruvic acid

high tyrosine in blood

Question 27

what is type 2 Tyrosinemia?

Answer 27

oculocutaneous tyrosinemia- photphobia and conjuctivitis during first year due to tyrosine crystals.

Question 28

what enzyme is deficient in Homocystinuria?

Answer 28

cystathionine-B-synthase

Question 29

what is in the urine in Homocystinuria?

Answer 29

homocystine and methionine

Question 30

what are the clinical features of Homocystinuria?

Answer 30

tall, long limbs
dislocated lens (ectopia lentis)- downward 
vascular abnormalities 
development and mental delay may occur and skeletal abnormalities

Question 31

what disease presents with elevated BCAAs and alpha ketoacids in the urine?

Answer 31

Maple Syrup Urine Disease

Question 32

what should you restrict in the diet of a MSUD patient?

Answer 32

protein- Branched chain amino acids

Question 33

Classic Galactosemia is a mutation in what?

Answer 33

galactose-1-phosphate uridyl transferase

Question 34

Nonclassical galactosemia is a mutation in what?

Answer 34

Galactokinase

Question 35

what is galactose important for?

Answer 35

cell membranes and lipids- especially the brain

Question 36

what are infants with Galactosemia unable to utilize?

Answer 36

galactose found in milk

Question 37

what do infants w/ Galactosemia develop?

Answer 37

mental retardation and cataracts, failure to thrive. (all in a few weeks)

Question 38

treatment of galactosemia?

Answer 38

restrict galactose in diet immediately. Only early diagnosis makes symptoms disappear.