Inborn Errors of Metabolism--Small Molecules Flashcards
What do all urea cycle disorders cause an elevation in? What should a person limit?
Ammonia
Limit protein
What is the genetic cause of Ornithine transcarbamylase (OTC) deficiency?
OTC (X-linked)
What blood tests do you perform for Urea Cycle Disorders?
Plasma amino acids
Ammonia levels
Orotic Acid Level
Is OTC on NBS?
No
What do you test for with Organic Acidemias?
Urine organic acids (will be high)
Low pH in the blood
Low CO2 (bicarbonate) in the blood
Acylcarnitine
What disorder smells like sweaty socks?
Isovaleric Acidemia
What is the treatment for organic acidemias?
Limit protein intake
Metabolic formula
Carnitine (clears toxins)
What disorder has problems breaking down leucine?
Isovaleric Acidemia
What is the gene involved in Isovaleric Acidemia?
IVD (AR)
What is the gene involved in Methylmalonic acidemia (MMA)?
MMUT (AR)
What are the genes related to Proprionic Acidemia?
PCCA
PCCB
What do the labs look like in Proprionic Acidemia?
Elevated C3 in acylcarnitine profile
Elevated 3-hydroxypropionate
Elevated glycine
High lactic acid
High anion gap
What disorder smells like a musty/mouse?
PKU
What disorder smells fishy?
Trimethylaminuria
What disorder smells like cabbage?
Tyrosinemia
What is the gene related to Phenylketonuria?
PAH (AR)
What is the gene related to Phenylketonuria?
PAH (AR)
What are the teratogenic effects of Maternal PKU syndrome?
Heart defects
Microcephaly
Developmental disability
What disorder has elevated phenylalanine levels?
Phenylketonuria (PKU)
What are the medications used to treat PKU?
Sapropterin
Palynziq
What is the gene associated with Tyrosinemia Type I?
FAH
What levels are increased in Tyrosinemia Type I and what is the chemical that causes injury in the body?
Tyrosine
Injury from succinylacetone
What does injury from succinylacetone cause in the body?
Liver cancer
What is the drug used in Tyrosinemia
Nitisinone clears toxins (never develop liver CA)
What is the gene associated with Alkaptonuria?
HGD
What test do you use to detect Alkaptonuria?
Urine organic acids
Homogentisic acid
What is the phenotype of Alkaptonuria?
Dark staining of urine and skin
Joint inflammation
Adult dx buildup in spine
Takes years to diagnose (adulthood)
What is the medication used to treat Alkaptonuria?
Nitisinone clears toxins
What genes are associated with Maple Syrup Urine Disease?
BCKDHA
BCKDHB
DBT
What amino acids build-up in Maple Syrup Urine Disease? Which one causes brain swelling?
Leucine, isoleucine, and valine
Leucine can cause brain swelling and can lead to coma.
What are the symptoms of Maple Syrup Urine Disease?
Failure to Thrive
Developmental delay
Seizures
Movement problems
What are the genetic causes of Non-Ketotic Hyperglycinemia?
AMT
GLDC
GCSH
What is the phenotype of Non-Ketotic Hyperglycinemia?
Intractable epilepsy
Devastating
What are the medications used to treat seizures in Non-Ketotic Hyperglycinemia?
Sodium Benzoate
Dextromethorphan
What amino acid builds up in Non-Ketotic Hyperglycinemia and why is the condition difficult to treat?
Glycine
The body naturally produces glycine so it is impossible to just limit it in the diet.
What blood tests do you look at in Homocystinuria?
Plasma amino acids (methionine)
Homocysteine levels
What is the phenotype of Homocystinuria?
Marfanoid habitus
Ectopia lentis and/or myopia
Thromboemolism (in adults)
What amino acids build up in Homocystinuria?
Increased homocystine and methionine
What drugs treat Homocystinuria?
Betaine
Vitamin B6 (pyridoxine)
What gene is associated with Glutaric Aciduria Type 1?
GCDH
What tests do you perform in Glutaric Aciduria Type 1?
Urine Organic Acids (glutaric acid)
What is the phenotype of Glutaric Aciduria Type 1?
Risk for basal ganglia stroke in childhood
Causes movement disorder
After age 6 years, stroke risk resolves and they can lead healthy lives (with diet regulation)
What do you limit in the diet of someone with Glutaric Aciduria Type 1?
Lysine and tryptophan free diet
Supplement with carnitine
What is the gene associated with Galactosemia?
GALT
What is the phenotype in Galactosemia?
Cataract
Jaundice
Liver damage
Lethargy
*E. coli sepsis
What is the Duarte variant in Galactosemia?
GALT variant associated with reduced enzyme activity but is typically asymptomatic (no management)
What labs are tested in Galactosemia?
GALT enzyme testing
Gal-1-p
Urine galactol
What is the gene related to Hereditary Fructose Intolerance?
ALDOB
What is the phenotype of Hereditary Fructose Intolerance?
N/V
Liver failure
High lactate
Hypoglycemia
What labs do you order with Hereditary Fructose Intolerance?
Only genetic testing
Cannot give individuals fructose
What is the gene associated with Wilson disease?
ATP7B (AR)
What is the mechanism of Wilson Disease?
Accumulation of Copper in the liver because ATP7B is transporter
What is the phenotype of Wilson disease?
*Kayser-Fleischer ring (accumulation of copper around iris)
Liver failure
Personality disorders/psychosis
Movement disorder
What medications are used to treat Wilson Disease?
Chelators (Penicillamine, Trientine)
Zinc
What do lab values look like for Wilson disease?
Low serum copper in blood
Low ceruloplasmin in blood
High urine copper
Copper levels are HIGH in tissue
What is the gene associated with Menkes disease?
ATP7A (X-linked)
What is the phenotype of Menkes disease?
Healthy until ~2 months
Loss of developmental milestones
Hypotonia
Seizures
FTT
Skin Laxity
*Kinky hair
What is the treatment for Menkes?
Copper histidinate
What do labs for Menkes disease look like?
Low serum copper in blood
Low ceruloplasmin in blood
High urine copper
(Looks the same as Wilson)
Which IEM are picked up by NBS?
Urea Cycle Disorders (Except OTC Def)
Organic Acid Disorders
Aminoacidopathies (Except Alkaptonuria)
Fatty Acid Oxidation Disorders
