TBL 1–Inborn Errors of Metabolism Flashcards
What are the types of inborn errors of metabolism?
- Fatty acid oxidation defects
- Galactosemia
- Glucose 6-phosphatase deficiency
- Glucose 6-phosphate dehydrogenase deficiency
- Glycolysis deficiencies
- Glycogen storage diseases (distinguishing liver from muscle)
- Hereditary fructose intolerance
- Mitochondrial DNA mutation
- Urea cycle defects
- Amino acid catabolism deficiencies
Each type has distinct clinical presentations and biochemical bases.
What is a key diagnostic test for fatty acid oxidation defects?
Plasma acylcarnitine profile
This test helps identify specific fatty acid oxidation disorders.
What is the biochemical basis of galactosemia?
Deficiency of galactose-1-phosphate uridylyltransferase
This leads to the accumulation of galactose-1-phosphate.
What is the primary clinical presentation of glucose 6-phosphate dehydrogenase deficiency?
Hemolytic anemia
This condition is triggered by oxidative stress.
Fill in the blank: Glycogen storage diseases can be distinguished between _______ and muscle types.
[liver]
Liver type affects blood glucose levels, while muscle type affects energy during exercise.
What is the metabolic pathway involved in hereditary fructose intolerance?
Fructose catabolism
It is linked to the deficiency of aldolase B.
True or False: Mitochondrial DNA mutations can affect energy metabolism.
True
These mutations can impair oxidative phosphorylation.
What is the main diagnostic test for urea cycle defects?
Plasma ammonia level
Elevated ammonia indicates a defect in the urea cycle.
What are the key components of glycolysis?
- Glucose
- 2 Pyruvate
- 2 ATP
- NADH
Glycolysis converts glucose to pyruvate, producing ATP and NADH.
What is the primary function of the urea cycle?
Detoxification of ammonia
The cycle converts ammonia to urea for excretion.
What are the roles of glycogen in the liver vs. muscle?
- Liver: Maintains blood glucose levels
- Muscle: Provides energy during exercise
Glycogen serves different physiological functions depending on the tissue.
Outline the metabolic pathway for phenylalanine catabolism.
Phenylalanine → Tyrosine → Dihydroxyphenylalanine (DOPA) → Dopamine → Norepinephrine
A deficiency in phenylalanine hydroxylase leads to phenylketonuria.
What is a general treatment strategy for inborn errors of metabolism?
Dietary management
This often involves restricting certain substrates or supplementing with missing products.
What pathway involves electron transport chain and TCA cycle?
Aerobic respiration
These pathways are crucial for ATP production in aerobic organisms.
What is the process of gluconeogenesis?
Synthesis of glucose from non-carbohydrate precursors
This occurs mainly in the liver and is crucial during fasting.
What diagnostic test is used for glycogen storage diseases?
Liver biopsy for enzyme activity
This helps determine the specific type of glycogen storage disease.
How do fatty acid oxidation defects present?
Infants: Fasting hypoglycemia, no elevate ketones (hypoketotic hypoglycemia)
Can cause seizures or coma
What test confirms hypoketotic hypoglecemia?
Plasma fatty acyl carnitine and free carnitine levels
-Built up unoxidized FA’s leak into the blood attached to carnitine-
How do you treat fatty acid oxidation defects?
Avoid fasting and eat slow digesting/absorbing carbs
Are fatty acid oxidation defects screened for at birth?
Yes
What is the most common fatty acid oxidation defect?
MCAD deficiency-medium chain acyl co-a dehydrogenase
How long after a meal do young kids start to synthesize ketones from FAs?
4-6 hours
What enzyme deficiency leads to galactosemia?
galactose 1-phosphate uridyltransferase
Symptoms of galactosemia?
Vomiting, lethargy, poor feeding with weight loss, jaundice, and hepatomegaly.
Cataracts and neurological impairments can also result if untreated
When does galactosemia present?
first few days/weeks of life
What gene is usually involved in galactosemia?
GALT
How is galactosemia treated?
Lactose free formula
What causes the pathology of galactosemia?
Accumulation of toxic substrates eg. galactitol
What enzyme is deficienct in GSD Type 1a (Von Gierke Disease)?
Glucose 6-phosphatase
When does Glucose 6 Phosphatase deficiency present?
2-6 months (when time between feeds extends)
Briefly describe the pathology of glucose 6 phosphatase deficiency
G6P must have the phosphate cleaved in order for glucose to exit the hepatocytes. Without G6-phosphatase, G6P is trapped and euglycemia can’t be maintained
What are the expected lab values in glucose 6 phosphatase?
Severe fasting hypoglycemia and elevated ketones.
Elevated lactate, triglycerides, and uric acid.
Hepatomegaly and renomegaly
What enzyme is involved in G6PD?
glucose 6-phosphate dehydrogenase
What are the symptoms of G6PD?
Anemia, jaundice, hematuria–especially when exposed to oxidative stress
What ethnicities is G6PD most prevalent in?
Northern African, Middle Eastern, and Southern Asian.
What histopathology is present in G6PD
Bite cells and Heinz bodies
