Inborn Errors of Metabolism

Question 1

How do organic acidurias present clinically?

Answer 1

Decomposition within the first two weeks of life

Acidosis, elevated anion gap, elevated lactic acid, hypoglycemia

Question 2

Name 4 acids that contribute to organic acidemia

Answer 2

Methylmalonic
Isovaleric
Proprionic
Glutaric acidemia

Question 3

List some clinical features of organic acidemia

Answer 3

Ketoacidosis
Elevated glycine
Hypoglycemia
Bone marrow suppression
Hyperammonemia (200-600

Question 4

Describe how PKU leads to an amino acidemia

Answer 4

When phenylalanine hydroxylase (PAH) is nonfunctioning, phenylalanine can no longer be converted to tyrosine and is instead shunted to phenylpyruvate which is subsequently converted to acids

Question 5

What is the main clinical problem with PKU?

Answer 5

The acids that accumulate in the blood are toxic to the brain. If untreated, infants can lose up to 50 IQ points within the first year of life

Question 6

What is the purpose of the urea cycle?

Answer 6

Dispose of nitrogen waste and the biosynthesis of arginine

Question 7

What is the main problem when the urea cycle doesn’t work properly?

Answer 7

The NH3 builds up in the blood

Question 8

What is the most common cause of a urea cycle deficiency?

Answer 8

X-linked OTC (ornithine transcarbamylase)

Question 9

Are people with a urea cycle deficiency alkalotic or acidotic?

Answer 9

Alkalotic- due to build-up of NH3 in the blood

NH3 can reach the 1000’s

Question 10

What are the symptoms of nonketotic hyperglycinemia?

Answer 10

Progressive lethargy, hypotonia, myotonic jerks and apnea

Some babies have hiccups

(elevated glycine)

Question 11

What are the findings on MRI of someone with nonketotic hyperglycinemia?

Answer 11

Agenesis of the corpus callosum

Majority of the infants die- if they survive they have profound mental retardation

Question 12

How are the ammonia, lactate and glucose levels in a baby with maple syrup urine disease?

Answer 12

NH3: normal or elevated
Lactate: normal
glucose: normal

Question 13

What does the baby have if the urine smells like sweaty feet?

Answer 13

Isovaleric acidemia

Question 14

What does the baby have if the urine smells like rotten cabbage?

Answer 14

Tyrosinemia

Question 15

What is the problem in medium-chain acyl-coenzyme A dehydrogenase deficiency (MCAD)?

Answer 15

Deficiency in an enzyme involved in mitochondrial fatty acid beta oxidation

Question 16

When do symptoms occur with MCAD?

Answer 16

After prolonged fasting

Question 17

Can MCAD be deadly?

Answer 17

2-3% of SIDS is caused by MCAD

Question 18

What are the symptoms of MCAD?

Answer 18

Hypoketotic hypoglycemia- Reye-like syndrome

Question 19

What is the treatment for MCAD deficiency

Answer 19

carnitine supplementation,

Question 20

Describe the symptoms associated with MCAD

Answer 20

Episodic illness with hypoglycemia usually between 3 months and 2 years of age- usually follows fasting of 12 hours or more with infectious illness

Acute episode starts with vomiting, lethargy, or even seizures

Can progress to coma rapidly

Question 21

Is the urine dip positive or negative for ketones with MCAD?

Answer 21

NEGATIVE- ketones come from beta oxidation of fatty acids. This process is busted in MCAD

Question 22

What is the MRI finding suggestive of glutartic acidemia?

Answer 22

Subdural hematomas

Question 23

Is the onset of glutaric acidemia immediate or delayed onset after birth?

Answer 23

Delayed onset

Question 24

What is the enzyme deficient in galactosemia?

Answer 24

Galactose-1-P-uridyl transferase (GALT)

Could also be GALK or GALE

Question 25

What toxic metabolite builds up in galactosemia?

Answer 25

Galactitol

Question 26

What positive lab findings are seen in the urine of someone with galactosemia?

Answer 26

Reducing substances (unmetabolized sugars)

Question 27

List the important clinical features of galactosemia

Answer 27

E. COLI SEPSIS Jaundice Hepatomegaly CATARACTS Untreated babies can rapidly progress to hepatic and death from sepsis or bleeding

Question 28

What is the treatment for galactosemia?

Answer 28

Lactose free diet During infancy- use Soy formula (breast milk has lactose)

Question 29

What is the enzyme deficient in glycogen disorder type I?

Answer 29

Von Gierke's disease; Enzyme is glucose-6-phosphatase. Glucose-6-P cannot be cleaved to glucose and is therefore stuck in the cell

Question 30

Describe the body of a baby with von gierks?

Answer 30

Shows failure to thrive- thin limbs and large abdomen

Question 31

What is the treatment for type I glycogen storage disease?

Answer 31

Prevent hypoglycemia with continuous feeds or cornstartch Restrict galactose and fructose in the diet

Question 32

What is the enzyme deficiency in type III glycogen storage disease?

Answer 32

Cori's disease: Deficiency of glycogen debranching enzymes. Complete degradation of glycogen is not possible --> abnormal glycogen/build up

Question 33

What are the clinical features of Cori's disease/

Answer 33

``` Hepatomegaly Hypoglycemia Short stature Skeletal myopathy Cardiomyopathy ```

Question 34

Which glycogen storage disease affects the liver?

Answer 34

I, 3, 4, 6

Question 35

Which glycogen storage diseases affect the skeletal muscle?

Answer 35

2, 5, 7

Question 36

What is the enzyme responsible for McArdle's disease?

Answer 36

Muscle phosphorylase --> results in reduced ATP generation by glycogenolysis

Question 37

What are the clinical signs of McArdle's?

Answer 37

Symptoms begin in the early 20's Exercise induced muscle cramps and exercise intolerance BURGUNDY COLORED URINE Labs show elevated CPK at rest, increases significantly with exercise

Question 38

What is the treatment for McArdle's?

Answer 38

Avoid strenuous exercise

Question 39

What is the enzyme deficient in type VII glycogen storage disease?

Answer 39

Phosphofructokinase deficiency- no conversion of fructose-6-phosphate to fructose-1,6-bisphosphate

Question 40

How does type VII differ from McArdle's?

Answer 40

Presents in childhood Hemolysis occurs Increases uric acid levels Exercise intolerance is much worse after a carbohydrate meal