Inborn Errors of Metabolism

Question 1

what kind of genetic defects are inborn errors of metabolism?

Answer 1

-autosomal recessive genetic defect

Question 2

what goes wrong with inborn errors of metabolism?

Answer 2

• occurs d/t the absence of an enzyme, cofactor, or transport protein which either degrades or converts one substance to another
• this absence results in either a toxic accumulation of the substrate or the deficiency itself can be toxic

Question 3

clinical presentation of inborn errors of metabolism

Answer 3

• prolonged and unexplained jaundice
• seizures
• GI disturbances (vomiting, poor feeding)
• failure to thrive
• disturbed acid/base status
• hypoglycemia
• reducing substances in the urine
• neurologic deterioration
• cardiac disorders - cardiomyopathy and arrhythmias
• acute liver disease

Question 4

How to diagnose inborn errors of metabolism?

Answer 4

• CBC/diff
• electrolytes
• arterial blood gas
• ammonia level
• lactate
• urine for reducing substances
• plasma amino acids
• urine organic acids

Question 5

How are phenylketonuria and maple syrup urine disease categorized?

Answer 5

disorders of amino acid metabolism

Question 6

what is phenylketonuria?

Answer 6

deficiency of phenylalanine hydroxylase

• function is to convert phenylalanine to tyrosine
• excess phenylalanine is toxic to CNS and there is a tyrosine deficiency

Question 7

What are the early symptoms of PKU?

Answer 7

• vomiting and poor feeding
• irritability
• musty smelling urine
• eczema

Question 8

How is PKU diagnosed?

Answer 8

newborn screen

-serum phenylalanine level > 25 mg/dL

Question 9

How is PKU treated?

Answer 9

• if treatment doesn’t being prior to 3-4 months, infant can have permanent deficits
• limit intake of phenylalanine (Lofenlac)

Question 10

What is maple syrup urine disease?

Answer 10

• deficiency of the enzyme which breaks down leucine, isoleucine, and valine
• toxic accumulation occurs

Question 11

What are the symptoms of maple syrup urine disease?

Answer 11

• severe neurologic symptoms
• vomiting
• metabolic acidosis
• urine smells like maple syrup

Question 12

How is maple syrup urine disease diagnosed?

Answer 12

• increased levels of leucine on urine amino acids

- state screen?

Question 13

How is maple syrup urine disease treated?

Answer 13

severely restrict amino acids

Question 14

Prognosis for maple syrup urine disease

Answer 14

• not good

- too late to treat by the time states screen comes back

Question 15

What are organic acids?

Answer 15

intermediate breakdown products of amino acids

Question 16

How are propionic acidemia and methylmatonic acidemia categorized?

Answer 16

disorders of organic acid metabolism

Question 17

symptoms of disorders of organic acid metabolism?

Answer 17

• metabolic acidosis
• feeding difficulties
• CNS deterioration
• hypoglycemia
• hyperammonemia
• hallmark is elevated anion gap

Question 18

treatment for disorders of organic acid metabolism

Answer 18

protein restriction

Question 19

prognosis for disorders of organic acid metabolism

Answer 19

-usually not caught soon enough, thus poor prognosis

Question 20

How is galactosemia categorized?

Answer 20

disorder of carbohydrate metabolism

Question 21

What is galactosemia?

Answer 21

-lack of enzyme necessary to breakdown galactose; increased levels of galactose are toxic

Question 22

what is the hallmark symptom of galactosemia?

Answer 22

reducing substances in the urine (galactose)

Question 23

if not treated, what can eventually happen to kids with galactosemia?

Answer 23

• cataracts (galactose accumulates in the aqueous humor)

- cirrhosis of the liver (galactose accumulates in the liver causing damage)

Question 24

how is galactosemia diagnosed?

Answer 24

• state screen
• increased serum galactose
• measurement of enzyme activity

Question 25

Prognosis of galactosemia

Answer 25

-not good, usually too late once disease is recognized

Question 26

about disorders of fatty acid oxidation (FAO)

Answer 26

• fatty acids are oxidized to produce energy during periods of fasting
• babies with these disorders cannot oxidize correctly; instead of a drop in blood sugar you have a life-threatening situation with significant hypoglycemia

Question 27

what is the most common type of inborn error (category)?

Answer 27

disorders of fatty acid oxidation (FAO)

Question 28

Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)

Answer 28

-inability to break down medium chain fatty acids

Question 29

treatment for MCADD

Answer 29

-avoid brief periods of fasting, constant glucose infusion if fasting, continuous tube feeds through night

Question 30

about disorders of hyperammonemia

Answer 30

-a defect in the urea cycle pathway

urea cycle functions to breakdown amino acids and get rid of ammonia

Question 31

symptoms of disorders of hypermmonemia

Answer 31

• poor feeding and emesis
• progressive CNS deterioration
• greatly elevated ammonia levels

Question 32

treatment for disorders of hyperammonemia

Answer 32

• stop all protein intake
• dialysis
• diet modification

Question 33

what is cystic fibrosis?

Answer 33

• a disorder causing dysfunction of exocrine glands

- autosomal recessive

Question 34

which organs does cystic fibrosis affects?

Answer 34

-any organ which secretes mucus

lungs, pancreas, intestines, biliary tract, GU tract

Question 35

clinical manifestations of cystic fibrosis

Answer 35

• failure to thrive
• bulky/fatty stools
• recurrent intestinal blockage
• prolonged jaundice
• early respiratory infections
• salty taste

Question 36

What is G6PD?

Answer 36

• an enzyme that converts glucose-6-phosphate dehydrogenase to glutathione
• glutathione protects the RBC from oxidation

Question 37

what is the most common enzyme deficiency?

Answer 37

G6PD

Question 38

pathophysiology of G6PD

Answer 38

• RBCs are damaged by oxidative substances like certain medications, infection, oxidizing agents
• this causes hemolytic anemia and subsequent hyperbilirubinemia