Genetic Disorders

Question 1

Describe classic PKU

Answer 1

Absence of phenylalaine hydroxylase
Mild form
Responds to proper diet

Question 2

Describe secondary PKU

Answer 2

Insufficient BH4 leads to BH2 deficiency
Abnormal response to diet
Progressive deterioration
May respond to BH4 treatments

Question 3

What disorders characterized by severe intellectual disability, microcephaly, light hair, bluish yes, convulsive movements, musty or mousy body odor? What is wrong if person responds to diet? What is wrong if person does not respond to diet?

Answer 3

PKU
Absence of phenylalaine hydroxylase (classic)
Insufficient BH4 (secondary)

Question 4

Describe characteristics of phenylketonuria

Answer 4

Severe intellectual disability: IQ

Question 5

What are the consequences of excess phenylalanine?

Answer 5

Toxic to infant neurological tissues
Inhibits:
Tyrosinase-> decrease in pigmentation
5HT decarboxylase-> decrease in serotonin synthesis
Glutamate decarboxylase-> decrease in GABA synthesis and possible decrease in all catecholamines
Damage occurs after birth: loss of 5 IQ units every 10 weeks of delayed treatment

Question 6

What can inhibit tyrosinase, 5HT decarboxylase, and glutamate decarboxylase?

Answer 6

Excess phenylalanine

Question 7

Describe maternal PKU

Answer 7

Phenylalanine crosses placenta
PAH in fetal liver is unable to convert PHE to TYR
Offspring: 92% mental retardation, 73% microcephaly

Question 8

Describe alkaptonuria

Answer 8

Autosomal recessive
Typically presents in 20-30’s
Discoloration of sclera (ochronosis)
Dark-colored urine (or darkens on standing)
Increase of homogentisate (due to defect in homogentisate oxidase)
Accumulation of hylaronic acid
Severe degeneration of cartilage of spine and other major joints (osteoarthritis)
Kidney disease

Question 9

What disorder is characterized by discoloration of sclera (ochronosis), dark-colored urine, osteoarthritis, and kidney disease? What enzyme is defective?

Answer 9

Alkaptonuria

Homogentisate oxidase

Question 10

Describe albinism

Answer 10

Autosomal recessive
Unable to synthesize melanin
Light hair, skin, eyes
Associated ocular defects
Increased risk of basal cell and squamous cell carcinomas
Defective tyrosinase

Question 11

What disorder has inability to synthesize melanin, associated ocular defects, and increased risk of basal cell and squamous cell carcinomas? What enzyme is defective?

Answer 11

Albinism

Tyrosinase

Question 12

Describe type I tyrosinemia

Answer 12

Infants have cabbage-like odor
Liver failure
Fumarylacetoacetate hyrolase is defective
Fumarylacetoacetate goes to succinylacetone in alternative pathway

Question 13

What disorder is when infants have a cabbage-like odor and liver failure? What enzyme is defective?

Answer 13

tyrosinemia type I

Fumarylacetoacetate

Question 14

Describe homocystinuria

Answer 14

Defect in cystathionine beta-synthase (classic)
Deep vein thrombosis
Stroke
Atherosclerosis
Marfan-like habitus (tall stature/long fingers)
Subluxation of lens is down and inward (vs up and outward for actual Marfan’s)
Mental retardation
Joint contractures

Question 15

What disorder is characterized by deep vein thrombosis, stroke, atherosclerosis, marfan-like habitus, subluxation of lens down and inward, mental retardation, and joint contracture? What enzyme is defective?

Answer 15

Homocystinuria

Cystathionine beta-synthase

Question 16

Describe maple syrup urine disease

Answer 16

Autosomal recessive
Symptoms appear 3-4 days after birth
Feeding difficulties, vomiting, lethargic
Progressive neurodegeneration
Abnormal muscle tone
Coma, death
Elevated BCAAs and alpha-ketoacids (urine and plasma)
Burnt sugar smell
High in Mennonite community

Question 17

What disease is characterized by elevated BCAAs and alpha-ketoacids, burnt sugar smell, feeding difficulties and vomiting, progressive neurodegeneration, abnormal muscle tone, coma, death, and is prevalent in Mennonite community? What is the defect?

Answer 17

Maple syrup urine disease

Alpha-ketoacid decarboxylase

Question 18

Describe galactosemia

Answer 18

Infants are unable to utilize galactose in milk (not converted to glucose for energy, so galactose accumulates)
Infant suffers from malnutrition, failure to thrive
Damage to liver, brain, eyes in first few days
Develops mental retardation
Cataracts within first few weeks
Vomiting, diarrhea, jaundice, hepatomegaly
Defects in galactokinase and galactose-1-phosphate uridyl transferase

Question 19

What disease is characterized by vomiting, diarrhea, jaundice, hepatomegaly, damage to liver, brain, eyes in first few days, mental retardation, and cataracts within first few weeks? What enzymes are defective?

Answer 19

Galactosemia

Galactokinase, galactose-1-phosphate uridyl transferase