9- Inborn Errors of Metabolism

Question 1

What is the enzyme deficiency in maple syrup urine disease?

Symptoms?

Cause of defective BCKD protien?

Answer 1

branched chain alpha ketoacid dehydrogenase

Urine smells of maple syrup. NERVOUS SYSTEM DEGENERATION. can case brain damage (encephalopathy) especially with fever, infection or fasting.

Recessive genetic disease

Question 2

What amino acids are not broken down and build up in maple syrup urine disease?

Answer 2

LIV

Leucine, isoleucine, valine

Question 3

How can thiamine help MSUD?

Answer 3

Branched chain alpha ketoacid dehydrogenase is thiamine responsive. Increases activity of enzyme.

Question 4

Characteristic symptoms of MSUD?

Prognosis?

Answer 4

Occur in newborns in first week of birth

Poor feeding habits, vommiting, poor weight gain

lethargy– deep sleep, sluggish

Sweet urine smell (MAJOR CHARACTERISTIC)

seizures, muscle spasms

Can come and go but could lead to brain damage if under physical stress.

Prognosis: Managable but could lead to death if not treated.

Question 5

Treatment for MSUD?

Answer 5

No foods with leucine, isoleucine, valine (lifelong)

Supplements

genetic counseling suggested

IV hyper-alimentation during time of metabolic decompensation

Question 6

What cannot be processed in PKU?

which enzyme is deficient?

Answer 6

Phenylalanine– builds up in blood stream and causes brain damage.

PAH- phenylalanine hydroxylase (phenylalanin > tyrosine)

Question 7

Treatment for PKU?

Answer 7

Diet low in phenylalanine. Eggs, milk and aspartame

Child can live normal life if eats diet low in phenylalanine. Especially when growing.

Question 8

In PKU, phenylalanine cannot be converted to tyrosine.

What is tyrosine usually used for in biosynthesis?

Answer 8

catecholamines, melanin, hormones, dopamine, epinephrine.

Question 9

PKU symptoms

Answer 9

Newborn show symptoms within a few months of birth

MENTAL RETARDATION, social/behavior problems.

Seizures, rocking, hyperactivity, rashes vomitting

stunted growth, SMALL HEAD,

FAIR SKIN, BLUE EYES (lack of melanin)

MUSTY ODOR in breath, skin or urine

Question 10

Test for PKU?

Answer 10

Guthrie card bloodspot– blood test for high levels of Phe

Question 11

Type I GSD?

Enzyme?

Symptoms?

Answer 11

Von Gierke’s Disease

Glycogen 6 phosphatase

severely enlarged liver, severe hypoglycemia, lactic acidosis, ketosis, hyperuricemia, hyperlipidemia

Question 12

Type II GSD?

Enzyme?

Symptoms?

Answer 12

Pope Disease

a1, 4 glucosidase, Lysosomal, debranching

liver and heart. Cardiac failure in infancy

Question 13

Type III GSD?

Enzyme?

Symptoms?

Answer 13

Cori’s Disease

Debranching enzyme

Liver and muscle (Cori cycle) similar to type one but more mild

Question 14

Type IV GSD?

Enzyme?

Symptoms?

Answer 14

Andersons’s

Branching enzyme

Liver cirrhosis, death by 2 years (usually) liver can’t handle the glycogen.

Question 15

Type V GSD?

Enzyme?

Symptoms?

Answer 15

McArdle’s disease

phosphorylase

Only Muscle. Muscle cramps, muscle fatigue

Question 16

Type VI GSD?

Enzyme?

Symptoms?

Answer 16

Hers (for hepatic)

Phosphorylase

Liver problems, similar to type 1 but more mild.

Question 17

Lesch Nyhan Disease, what enzyme is deficient and why does it cause problems?

Symptoms?

Answer 17

HGPRT- part of PURINE salvage pathway, the majority of guanine and hypoxanthine should go through here but can’t, increase uric acid.

Spastic cerebral palsy, SELF-MUTILATION, hyperuricemia, Early death

Question 18

Ornithine transcarbamoylase deficiency

Answer 18

Hereditary, X lined recessive, Urea cycle disorder (AA)

Orthinine Transcarbomoylase:
carbamoyl phosphate > citrulline

Orotic aciduria and increase uracil (gout)
hyperammonemia 
Blood glutamine increase 
BUN decreased 
Cerebral edema 
Lethargy convulsions, coma death

Question 19

Carbamoylase Phosphate synthetase I deficiency

Answer 19

Hereditary, autosomal recessive (AA metabolism)

Inability for ammonia to be metabolized via urea cycle

No orotic aiduria 
hyperammonemia 
Blood glutamine increase 
BUN decreased 
Cerebral edema 
Lethargy convulsions, coma death