Lecture 23: Metabolic Disorders Flashcards
How are most metabolic disorders inherited?
Autosomal recessive.
Exception: Fabry’s is X-linked.
What characterizes metabolic disorders?
- Absence or abnormality of an enzyme or its cofactor.
- Accumulation or deficiency in a specific metabolite.
What are the three primary products of carbohydrate metabolism?
- Glucose
- Galactose
- Fructose
What is sorbitol an alcohol of?
Fructose
Where is glycogen stored in the body?
- Liver
- Muscle
What do glycogen storage disorders result in?
Accumulation of glycogen in the tissues due to a defect in metabolism.
What is the typical clinical presentation of a GSD in the liver?
- Fasting hypoglycemia and ketosis that improves with eating.
- Possible hepatomegaly
What is the typical clinical presentation of a GSD in the muscles?
- Delayed growth in children
- Exercise intolerance
- Progressive weakness
What labs would we expect for a GSD pt?
- Fasting hypoglycemia
- Elevated LFTs and CPK
How do we generally manage a GSD?
- Avoid hypoglycemia
- Enzyme replacement for specific ones.
- Symptomatic therapy
What are the 3 subtypes of fructosemia?
- Deficiency of fructose 1,6-diphosphatase (FDPase)
- Deficiency of fructose 1,6-biphosphatase aldolase (Aldolase B/Hereditary fructose intolerance)
- Deficiency of fructokinase (Essential fructosuria)
What is the mechanism of FDPase deficiency and the result?
Mechanism: Conversion of Fructose 1,6-biphosphate to Fructose 6-phosphate.
Results in inadequate gluconeogenesis during periods of fasting.
How does a FDPase deficiency present clinically?
- Hypoglycemia symptoms
- Acidosis symptoms (buildup of lactate)
How do we manage FDPase deficiency?
- Avoid fructose
- Avoid fasting for too long
What is the effect of an aldolase B or fructose 1,6-biphosphatase aldolase deficiency?
Toxic accumulation of Fructose-1-phosphate in the Liver, Kidney and SI, causing cell death.
How does an Aldolase B deficiency present clinically?
Ingestion of fruit or sweetened cereal leads to…
- Severe abdominal pain
- Failure to thrive
- Jaundice and hepatomegaly
- Hypoglycemia
How do we diagnose and manage an aldolase B deficiency?
Genetic testing to diagnose.
Management includes complete avoidance of fructose and sucrose.
What is the most benign form of fructosemia?
Lack of fructokinase, aka essential fructosuria.
What is the pathophysiology of essential fructosuria?
Cannot convert fructose to anything, so you pee it out instead.
How do you manage essential fructosuria?
No management needed, as you will pee it out.
What causes galactosemia?
Autosomal recessive defect of chromosome 9p13.
What is galactosemia?
Toxic accumulation of galactose-related molecules due to an inability to metabolize it.
Where does galactose typically come from?
- Milk
- Baby formula
- Celery, kiwi, plum, avocado, and figs.
What 3 enzyme deficiencies result in galactosemia?
- Galactose-1-phosphate uridyl transferase (GALT), AKA Type 1 galactosemia, as it is the MC and severe.
- Galactokinase (GALK), Type 2.
- Galactose epimerase (GALE), Type 3.