Inborn Errors of metabolism- Lecture 84 Flashcards
What are inborn errors of metabolism?
inherited defects in one of the critical components of a basic metabolism pathway resulting in clinical disease
What are the principles of treatment for inborn errors of metabolism?
restrict substrate provide cofactors provide product replace enzyme provide alternative routes of elimination treat secondary effects
What are the disorders of protein metabolism discussed?
Phenylketonuria (PKU)
Tetrahydrobiopterin deficiency
Organic Acidemias
Ornithine Transcarbamylase (OTC deficiency)
What are the disorders of carbohydrate metabolism that were discussed?
galactosemia GSD 1a (Von Gierke's disease)
What are the disorders of fatty acid oxidation discussed?
Medium chain Acyl CoA Dehydrogenase Deficiency (MCAD)
What are the symptoms of PKU?
severe intellectual disability with irritable and destructive behavior; hypopigmentation; ferric chloride added to urine turns green (rather than red)
How is PKU treated?
restrict phenylalanine
provide supplemental tyrosine
new alternative enxzyme recently approved (phenylalanine ammonium lyase)
What causes PKU?
deficiency of phenylalanine hydroxylase (AR)
What is Maternal PKU?
fetal exposure to elevated levels of maternal phenylalanine resulting in birth defects (microcephally, congenital heart disease, craniofacial abnormalities, small for gestational age)
What is the cause of Tetrahydrobiopterin deficiency?
deficiency of tetrahydrobiopterin (cofactor for phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase) resulting in increases in phenylalanine and decreases in dopamine and serotonin
How do you treat Tetrahydrobiopterin deficiency?
tetrahydrobiopterin replacement with serotonin and dopamine precursors
What is organic acidemia?
inborn error of amino acid metabolism in which the pathway intermediate that is elevated is a non-amino organic acid
What is classic propionic acedemia?
deficiency of proprionyl CoA carboxylase presenting with emesis, severe metabolic acidosis, and accumulation of toxic propionic acid metabolites
normally results in intellectual disability, recurrent metabolic decompensation, and end organ failure
What causes recurrent metabolic decompensation in patients with classic pripionyl acidemia?
infection, protein overload, essential aa deficiency, severe injury, surgery, and fasting
What is OTC deficiency?
X-linked deficiency of ornithine transcarbamylase that results in toxic hyperammonemia –> severe and permanent brain damage or death
How do you treat calssic propionic acedemia?
VOMIT free diet, antibiotics to decrease gut propiogenic bacteria
provide biotin
provide carnitine to bind and elimicate propionic acid
treat secondary effects with ammonia detox and bicarbonate to neutralize acid
How do you treat OTC deficiency?
restrict all protein
provide citrulline
liver transplant replaces enzyme
eliminate ammonia by dialysis and ammonia scavenging medications
What is classic galactosemia?
deficiency of galactose-1-phosphate uridyltransferase resulting in elevated levels of galactose-1-phosphate
What are symptoms of classic galactosemia?
newborn coagulopathy liver dysfunction/failure cataracts E. coli sepsis primary ovarian failure learning disabilities
How do you treat classic galactosemia?
lactose and galactose free diet
antibiotics for E. coli
appropriate coagulitive therapy in newborns
What is GSD-1a/Von Gierke’s disease?
deficiency of G-6-Pase resulting in severe hypoglycemia, hepatomegaly, growth restriction, osteopenia, renal calculi, pancreatitis, and gout
displays as increased lactate, triglycerides, uric acid in blood
How do you treat GSD-1?
provide frequent feeds, cornstarch, gastrostomy tubes for overnight feeds
allopurinol (treat uric acid)
maintain nomral acid base status
antilipidemic medications (for elevated triglycerides)
What is medium chain AcylCoA Dehydrogenase Deficiency (MCAD)?
most common fatty acid oxidation defect
presents as fever, liver failure, encephalopathy, hyperammonemia
normally will cause sudden death in ~18% of all pediatric age groups
How do you treat MCAD?
avoidance of fasting
