Inborn Errors of Metabolism Flashcards
How do organic acidurias present clinically?
Decomposition within the first two weeks of life
Acidosis, elevated anion gap, elevated lactic acid, hypoglycemia
Name 4 acids that contribute to organic acidemia
Methylmalonic
Isovaleric
Proprionic
Glutaric acidemia
List some clinical features of organic acidemia
Ketoacidosis Elevated glycine Hypoglycemia Bone marrow suppression Hyperammonemia (200-600
Describe how PKU leads to an amino acidemia
When phenylalanine hydroxylase (PAH) is nonfunctioning, phenylalanine can no longer be converted to tyrosine and is instead shunted to phenylpyruvate which is subsequently converted to acids
What is the main clinical problem with PKU?
The acids that accumulate in the blood are toxic to the brain. If untreated, infants can lose up to 50 IQ points within the first year of life
What is the purpose of the urea cycle?
Dispose of nitrogen waste and the biosynthesis of arginine
What is the main problem when the urea cycle doesn’t work properly?
The NH3 builds up in the blood
What is the most common cause of a urea cycle deficiency?
X-linked OTC (ornithine transcarbamylase)
Are people with a urea cycle deficiency alkalotic or acidotic?
Alkalotic- due to build-up of NH3 in the blood
NH3 can reach the 1000’s
What are the symptoms of nonketotic hyperglycinemia?
Progressive lethargy, hypotonia, myotonic jerks and apnea
Some babies have hiccups
(elevated glycine)
What are the findings on MRI of someone with nonketotic hyperglycinemia?
Agenesis of the corpus callosum
Majority of the infants die- if they survive they have profound mental retardation
How are the ammonia, lactate and glucose levels in a baby with maple syrup urine disease?
NH3: normal or elevated
Lactate: normal
glucose: normal
What does the baby have if the urine smells like sweaty feet?
Isovaleric acidemia
What does the baby have if the urine smells like rotten cabbage?
Tyrosinemia
What is the problem in medium-chain acyl-coenzyme A dehydrogenase deficiency (MCAD)?
Deficiency in an enzyme involved in mitochondrial fatty acid beta oxidation
When do symptoms occur with MCAD?
After prolonged fasting
Can MCAD be deadly?
2-3% of SIDS is caused by MCAD
What are the symptoms of MCAD?
Hypoketotic hypoglycemia- Reye-like syndrome
What is the treatment for MCAD deficiency
carnitine supplementation,
Describe the symptoms associated with MCAD
Episodic illness with hypoglycemia usually between 3 months and 2 years of age- usually follows fasting of 12 hours or more with infectious illness
Acute episode starts with vomiting, lethargy, or even seizures
Can progress to coma rapidly
Is the urine dip positive or negative for ketones with MCAD?
NEGATIVE- ketones come from beta oxidation of fatty acids. This process is busted in MCAD
What is the MRI finding suggestive of glutartic acidemia?
Subdural hematomas
Is the onset of glutaric acidemia immediate or delayed onset after birth?
Delayed onset
What is the enzyme deficient in galactosemia?
Galactose-1-P-uridyl transferase (GALT)
Could also be GALK or GALE