Inborn Errors of Metabolism Handout

Question 1

MCAD ethnic

Answer 1

Northern european

Question 2

MCAD clinical presentation

Answer 2

Develop normally until prolonged fast (often with illness)
Develop hypoketotic hypoglycemia
Presents with altered mental status and lethargy

Question 3

Diagnosis of MCAD

Answer 3

Screening
Lab eval will reveal non-ketotic hypoglycemia
C6-C10 acylcarnitines

Question 4

Management of MCAD

Answer 4

Avoid fasting

Question 5

VLCAD def

Answer 5

Similar to MCAD with fat deposition into organs
Hepatomegaly and liver dysfunction, cardiomyopathy, muscle weakness
C14-C16 acylcarnitines
Restrict dietary fats AND avoid fasting…supplement with medium chain

Question 6

Clinical manifestations of organic acid disorders

Answer 6

Lethargy, vomiting, and failure to thrive
As progession, hypotonia, seizures, and coma
Metabolic acidosis with high anion gap and ketosis
Could also have elevated lactate, hyperammonemia, and/or hypoglycemia

Question 7

Diagnosis of organic acid disorders

Answer 7

Most by screening but could develop after

Question 8

Propionic acidemia

Answer 8

Defect in propionyl-CoA carboxylase leads to defect in Ile, Val, Met, and Thr metabolism
Measure urine for propionic acid
Stop all protein intake and administer dextrose

Question 9

Methylmalonic acidemia

Answer 9

Methylmalonic acid AND propionic acid in the urine
Adminster Dextrose and stop protein
Vitamin B12 as supplemnt

Question 10

PKU clinical manifestation

Answer 10

Microcephaly and developmental delay

Adults may have risk of mood disorders or cog dysfunction

Question 11

PKU diagnosis

Answer 11

Usually screening…see increase in Phe

Question 12

Management of PKU

Answer 12

Administer BH4 (cofactor)…limit Phe intake

Question 13

MSUD clinical

Answer 13

Lethargy and irritability, seizures and poor feeding…hypertonicity

Question 14

Diagnosis of MSUD

Answer 14

Measurement of plasma AAs show elevated Leu, Ile, and Val (alo alloisoleucine)
typically screened but could develop after

Question 15

Managment of MSUD

Answer 15

Stop all protein intake and administer dextrose

Long term is to administer thiamine and limit

Question 16

Tyrosinemia 1 clinical

Answer 16

Failure to thirive and hepatomegaly

Kidney toxicity from renal tubular dysfunction presenting as renal tubular acidosis and hypophosphatemia

Question 17

Diagnosis of tyrosinemia 1

Answer 17

Typically screened
Elevated tyrosine and methionine
Also elevated succinylacetone

Question 18

Managment of tyrosinemia 1

Answer 18

Reduce met, tyr, and phe

Nitisinone inhibits a dioxygenase whcih decreases generation of toxic fumarylacetoacetate

Question 19

GSD type 1 enzyme, clinical, labs

Answer 19

G-6-pase
Hepatomegaly with failure to thrive
Severe hypoglycemia

Question 20

GSD type 3 enzyme, clinical, labs

Answer 20

Debranching enzyme
Hepatomegalym, failure to thrive, muscle weakness, hypotonia
Mild hypoglycemia

Question 21

GSD type 4 enzyme clinical labs

Answer 21

Branching enzyme
Liver failure
Hypoglycemia occurs late

Question 22

GSD Type 6 enzyme clinical labs

Answer 22

Hepatic phosphorylase
Hepatomaegaly and failure to thrive
Mild hypoglycemia

Question 23

Diagnosis of GSDs

Answer 23

Look for hypoglycemia with hypertrigluceridemia, lactic acidosis and hepatomegaly…DNA testing to confirm

Question 24

Management of GSDs

Answer 24

Maintain glucose levels to prevent hypglycemia…uncooked corn starch

Anderson has no therapy and need liver transplant

Question 25

Galactosemia inheritance

Answer 25

Auto rec

Question 26

Galactosemia clincal

Answer 26

After breast feeding 
Jaundice, poor feeding, and vomiting 
Hepatomegaly 
Cataracts 
Hyperbilirubinemia, abnormal liver function, reducing substances in urine 
Ketones absent

Question 27

Galactosemia diagnosis

Answer 27

Newborn screening but may develop after weeks

MEasure GALT activity

Question 28

Management of galactosemia

Answer 28

Eliminate galactose…soy-based formulas

Question 29

Hereditary fructose intolerance clinical

Answer 29

Recurrent vomiting and poor feeding after intor of fructose or sucrose into diet
Lethargy and seizures
Hepatomegaly, jaundice and renal dysfunction
Hypoglycemia, hyperuricemia, metabolic acidosis and/or lactic acidosis reducing substances in urine …ketones absent or normal

Question 30

Diangosis of hereditary fructose intolernace

Answer 30

DNA testing

Question 31

Managment of hereditary fructose intolerance

Answer 31

Eliminate fructose from diet