Aminoacidopathies & Organic Acidemias

Question 1

What are the 3 organic acid disorders?

Answer 1

Methylamonic acidemia (MMA)
Propionic acidemia (PA)
Isovaleric acidemia (IA)

Question 2

Mutations in what gene cause MMA?

Answer 2

MUT

Question 3

Mutations in what gene cause PA?

Answer 3

PCCA
PCCB

Question 4

Mutations in what gene cause IA?

Answer 4

IVD

Question 5

What biochemical testing is ordered when an OAD is suspected?

Answer 5

Urine organic acids

Question 6

What biochemical findings might we see with OADs?

Answer 6

Organic acid elevation (specific to the disorder)
Low pH
Low CO2 (bicarbonate)

Question 7

What does isovaleric acid smell like?

Answer 7

Sweaty socks :)

Question 8

What are the aminoacidopathies?

Answer 8

PKU
Tyrosinemia Type 1
Alkaptonuria
Maple Syrup Urine Disease
Non-Ketotic hyperglycinemia
Homocystinuria
Glutaric aciduria Type 1

Question 9

What amino acid cannot be broken down in PKU? What toxin builds up?

Answer 9

AA: Phenylalanine
Toxin: Phenylalanine again

Question 10

What amino acid cannot be broken down in Tyrosinemia Type 1? What toxin builds up?

Answer 10

AA: Tyrosine
Toxin: Succinylacetone

Question 11

What amino acid cannot be broken down in Alkaptonuria? What toxin builds up?

Answer 11

AA: Tyrosine
Toxin: Homogentisic acid

Question 12

What amino acid cannot be broken down in Maple Syrup Urine Disease? What toxin builds up?

Answer 12

AA: “Branched chain” amino acids (Leucine, Isoleucine, Valine)
Toxin: Leucine

Question 13

What amino acid cannot be broken down in Non-Ketotic Hyperglycinemia? What toxin builds up?

Answer 13

AA: Glycine
Toxin: Also glycine

Question 14

What amino acid cannot be broken down in Homocystinuria? What toxin builds up?

Answer 14

AA: Methionine
Toxin: Homocysteine

Question 15

What amino acid cannot be broken down in Glutaric Acidemia Type 1? What toxin builds up?

Answer 15

AA: Lysine
Toxin: Glutaric acid

Question 16

What biochemical testing would be ordered for a suspected aminoacidopathy?

Answer 16

(Mostly) plasma amino acids
Levels of the toxin

Question 17

Mutations in what gene cause PKU?

Answer 17

PAH

Question 18

What smell do high Phe levels cause?

Answer 18

“Mousy” odor

Question 19

What are features of maternal PKU syndrome?

Answer 19

Heart defects
Microcephaly
Developmental disability

Question 20

Mutations in what gene cause tyrosinemia type 1?

Answer 20

FAH

Question 21

What organ does succinylacetone damage in Tyrosinemia type 1?

Answer 21

Liver; often leads to cancer

Question 22

What are the typical aspects of treatment for aminoacidopathies?

Answer 22

Limit the precursors: low protein diet, metabolic diet

Clear toxins: medications that clear out the toxin

Question 23

Mutations in what gene cause alkaptonuria?

Answer 23

HGD

Question 24

What biochemical testing detects alkaptonuria?

Answer 24

Urine organic acids (homogentisic acid) – NOT amino acid profile since there is no AA buildup

Question 25

When is typical onset of alkaptonuria?

Answer 25

Adult-onset

Question 26

Mutations in what genes cause Maple Syrup Urine Disease?

Answer 26

BCKDHA BCKDHB DBT

Question 27

What symptoms can leucine buildup cause in MSUD? What other symptoms can this cause?

Answer 27

Brain swelling, can lead to coma, death FTT, dev delay, seizures, movement problems, maple syrup odor ("sweet smell") in urine and earwax

Question 28

Mutations in which genes cause Non-Ketotic Hyperglycinemia?

Answer 28

AMT GLDC GCSH

Question 29

What symptoms/features do we see in N-KH?

Answer 29

Intractable epilepsy Profound cognitive disability

Question 30

Mutations in what gene cause homocystinuria?

Answer 30

CBS

Question 31

What features do we see in homocystinuria?

Answer 31

Marfanoid habitus Strokes (typically adulthood)

Question 32

Mutations in what gene cause Glutaric Aciduria Type 1?

Answer 32

GCDH

Question 33

What neurologic event do we see in GA Type 1?

Answer 33

Childhood stroke of the basal ganglia; often loss of motor control afterwards

Question 34

At what age does the stroke risk resolve in GA1?

Answer 34

6 years old "If they can go first 6 years without a stroke, they're healthy"