Genetics- Metabolic Disorders of the newborn- Dr. Adkison Flashcards
where are Housekeeping genes expressed?
in all cell types. expressed all the time and regulated
giving a recombinant enzyme, glucocerebrosidase, for a pt w/ Type 1 Gauchers is an example of what method of treating inherited enzyme mutation?
replacement of mutant protein
what are the essential amino Acids?
PVT. TIM HALL
phenylalanine, valine, tryptophan, threonine, isoleucine, methionine, histidine, arginine, leucine, lysine
increased amounts of what in urine causes a mousey odor of the urine? what disorder is this seen in?
Phenylalanine- in Phenylketonuria
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?
Phenylketonuria
Phenylketonuria is a mutation in what enzyme?
phenylalanine hydroxylase
Clinical expectations with PKU type 1?
elevated phenylalanine, reduced or normal tyrosine, normal at birth, toxic to infant neurological tissue. damage occurs after birth (0-6 months)
what is the Guthrie test? whats a positive outcome?
bacterial inhibition assay that tests for PKU. >4mg/100dL then suspect PKU
what do PKU patients have to limit their intake in their diet?
Phenylalanine
what else causes a positive Guthrie test?
high PHE, High TYR (low birth weight, protein formula, vit. C deficiency) liver disease, Galactosemia
If positive Guthrie test reveals elevated PHE. what should you perform next? what result is a typical PKU patient?
blood test. >15mg/100ml PHE and <5 mg/100ml TYR
Major clinical finding in type 2 hyperphenylalanine?
abnormal response to diet. progressive detioration of brain fxn leading to death
what is deficient in TYPE 2 hyperphenylalanine? what is it required for?
Dihydropteridine Reductase
BH4 synthesis, required for tyrosine and tryptophan pathways –> neurotransmitters
elevated PHE reduced or normal TYR reduced BH4 elevated BH2 dopamine, serotonin levels low what disorder has this clinical presentation?
type 2 hyperphenylalanemia
elevated neopterin reduced sepiapterin reduced BH4 reduced BH2 elevated PHE
TYPE 3 hyperphenylalanemia
offspring with mental retardation and microcephaly due to maternal PKU, is due to what mechanism?
PHE crosses the placenta and Phenylalanine hydroxylase from fetal liver is unable to convert to tyrosine
what inheritence is PKU?
autosomal recessive
what is the mildest form of phenylalanine hydroxylase deficiency?
non- PKU HyperPhenylAlanine
a child presents with dark urine and increased levels of homogentistic acid?
Alkaptonuria
Alkaptonuria is a deficiency in what enzyme?
homogentisic acid oxidase
what is a deficiency in tyrosinase?
Albinism. can’t form melanins from tyrosine
what are the activities of tyrosinease in Type 1A classic albinism? and Type 1B classic albinism?
1A- tyrosinase activity is negative
1B- activity is reduced
what is the most common form of albinism in the world? what is the activity of tyrosinase?
albinism type 2
activity is positive
what is present in type 2 to differentiate it from type 1B?
presence of pigmented nevi. (difficult to ID in blacks.) hair will be yellow or very light colored
what is the deficient enzyme in Tyrosinemia?
p-hydroxyphenypyruvic oxidase
what is secreted in the urine in Tyrosinemia? whats high in newborns blood?
p-hydroxyphenylpyruvic acid
high tyrosine in blood
what is type 2 Tyrosinemia?
oculocutaneous tyrosinemia- photphobia and conjuctivitis during first year due to tyrosine crystals.
what enzyme is deficient in Homocystinuria?
cystathionine-B-synthase
what is in the urine in Homocystinuria?
homocystine and methionine
what are the clinical features of Homocystinuria?
tall, long limbs dislocated lens (ectopia lentis)- downward vascular abnormalities development and mental delay may occur and skeletal abnormalities
what disease presents with elevated BCAAs and alpha ketoacids in the urine?
Maple Syrup Urine Disease
what should you restrict in the diet of a MSUD patient?
protein- Branched chain amino acids
Classic Galactosemia is a mutation in what?
galactose-1-phosphate uridyl transferase
Nonclassical galactosemia is a mutation in what?
Galactokinase
what is galactose important for?
cell membranes and lipids- especially the brain
what are infants with Galactosemia unable to utilize?
galactose found in milk
what do infants w/ Galactosemia develop?
mental retardation and cataracts, failure to thrive. (all in a few weeks)
treatment of galactosemia?
restrict galactose in diet immediately. Only early diagnosis makes symptoms disappear.
