Inborn Errors of metabolism- Lecture 84

Question 1

What are inborn errors of metabolism?

Answer 1

inherited defects in one of the critical components of a basic metabolism pathway resulting in clinical disease

Question 2

What are the principles of treatment for inborn errors of metabolism?

Answer 2

restrict substrate
provide cofactors
provide product
replace enzyme
provide alternative routes of elimination
treat secondary effects

Question 3

What are the disorders of protein metabolism discussed?

Answer 3

Phenylketonuria (PKU)
Tetrahydrobiopterin deficiency
Organic Acidemias
Ornithine Transcarbamylase (OTC deficiency)

Question 4

What are the disorders of carbohydrate metabolism that were discussed?

Answer 4

galactosemia
GSD 1a (Von Gierke's disease)

Question 5

What are the disorders of fatty acid oxidation discussed?

Answer 5

Medium chain Acyl CoA Dehydrogenase Deficiency (MCAD)

Question 6

What are the symptoms of PKU?

Answer 6

severe intellectual disability with irritable and destructive behavior; hypopigmentation; ferric chloride added to urine turns green (rather than red)

Question 7

How is PKU treated?

Answer 7

restrict phenylalanine
provide supplemental tyrosine
new alternative enxzyme recently approved (phenylalanine ammonium lyase)

Question 8

What causes PKU?

Answer 8

deficiency of phenylalanine hydroxylase (AR)

Question 9

What is Maternal PKU?

Answer 9

fetal exposure to elevated levels of maternal phenylalanine resulting in birth defects (microcephally, congenital heart disease, craniofacial abnormalities, small for gestational age)

Question 10

What is the cause of Tetrahydrobiopterin deficiency?

Answer 10

deficiency of tetrahydrobiopterin (cofactor for phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase) resulting in increases in phenylalanine and decreases in dopamine and serotonin

Question 11

How do you treat Tetrahydrobiopterin deficiency?

Answer 11

tetrahydrobiopterin replacement with serotonin and dopamine precursors

Question 12

What is organic acidemia?

Answer 12

inborn error of amino acid metabolism in which the pathway intermediate that is elevated is a non-amino organic acid

Question 13

What is classic propionic acedemia?

Answer 13

deficiency of proprionyl CoA carboxylase presenting with emesis, severe metabolic acidosis, and accumulation of toxic propionic acid metabolites
normally results in intellectual disability, recurrent metabolic decompensation, and end organ failure

Question 14

What causes recurrent metabolic decompensation in patients with classic pripionyl acidemia?

Answer 14

infection, protein overload, essential aa deficiency, severe injury, surgery, and fasting

Question 15

What is OTC deficiency?

Answer 15

X-linked deficiency of ornithine transcarbamylase that results in toxic hyperammonemia –> severe and permanent brain damage or death

Question 16

How do you treat calssic propionic acedemia?

Answer 16

VOMIT free diet, antibiotics to decrease gut propiogenic bacteria
provide biotin
provide carnitine to bind and elimicate propionic acid
treat secondary effects with ammonia detox and bicarbonate to neutralize acid

Question 17

How do you treat OTC deficiency?

Answer 17

restrict all protein
provide citrulline
liver transplant replaces enzyme
eliminate ammonia by dialysis and ammonia scavenging medications

Question 18

What is classic galactosemia?

Answer 18

deficiency of galactose-1-phosphate uridyltransferase resulting in elevated levels of galactose-1-phosphate

Question 19

What are symptoms of classic galactosemia?

Answer 19

newborn coagulopathy
liver dysfunction/failure
cataracts
E. coli sepsis
primary ovarian failure
learning disabilities

Question 20

How do you treat classic galactosemia?

Answer 20

lactose and galactose free diet
antibiotics for E. coli
appropriate coagulitive therapy in newborns

Question 21

What is GSD-1a/Von Gierke’s disease?

Answer 21

deficiency of G-6-Pase resulting in severe hypoglycemia, hepatomegaly, growth restriction, osteopenia, renal calculi, pancreatitis, and gout
displays as increased lactate, triglycerides, uric acid in blood

Question 22

How do you treat GSD-1?

Answer 22

provide frequent feeds, cornstarch, gastrostomy tubes for overnight feeds
allopurinol (treat uric acid)
maintain nomral acid base status
antilipidemic medications (for elevated triglycerides)

Question 23

What is medium chain AcylCoA Dehydrogenase Deficiency (MCAD)?

Answer 23

most common fatty acid oxidation defect
presents as fever, liver failure, encephalopathy, hyperammonemia
normally will cause sudden death in ~18% of all pediatric age groups

Question 24

How do you treat MCAD?

Answer 24

avoidance of fasting