Small Molecules Flashcards
What is the most common urea cycle disorder?
OTC
- X-linked
ammonia builds up and can get to the brain
What can we test to detect OTC?
(X-linked)
Plasma amino acids
Ammonia level
Orotic acid level
What are some treatment options for OTC?
- limit precursors –> low protein diet + metabolic formula
- Meds help Clear toxins –> ammonul, phenylbutryate, benzoate
What Urea cycle disorder is NOT on NBS?
OTC
What does Acidemia mean?
acid in the blood
What tests can we order for Organic Acid Disorders?
Urine organic acids
Will observe LOW pH and LOW CO2 bicarbinate
The name of the Org Acid Disorder tells you?
tells what acid is accumulating - ex: Methylmalonic Acidemia = accum of methylmalonic acids
Org Acids are coming from breakdown of what?
breakdown of certain amino acids
What are some treatment options for Organic Acid Dis?
- Limit precursors
–> low protein diet
–> metabolic formula - Meds to Clear toxins –> carnitine
What is the most common aminoacidopathy?
PKU
How are we (generally) testing for Aminoacidopathies?
Plasma amino acids
Levels of the toxin
Aminoacidopathy: PKU - what cannot get broken down? What is the toxin?
Phenylalanine
Phenylalanine = toxin
(PAH)
Aminoacidopathy: Tyrosinemia Type 1 - what cannot get broken down? What is the toxin?
Tyrosine
Succinylacetone = toxin
Aminoacidopathy: Alkaptonuria - what cannot get broken down? What is the toxin?
Tyrosine
Homogentisic acid = toxin
Aminoacidopathy: MSUD - what cannot get broken down? What is the toxin?
branched chain amino acids (Leucine, Isoleucine, Valine)
Leucine = toxin
Aminoacidopathy: Non-Ketotic Hyperglycinemia (NKH) - what cannot get broken down? What is the toxin?
Glycine
Glycine = toxin
Aminoacidopathy: Homocystinuria - what cannot get broken down? What is the toxin?
Methionine
Homocysteine = toxin
Aminoacidopathy: Glutaric Acidemia Type 1 - what cannot get broken down? What is the toxin?
Lysine
Glutaric acid = toxin
High Phe levels —> what smell?
Mousy odor
What is the danger to excess phenylalanine
Builds up in brain
ADHD, anxiety
Severe cog disability
If Mom does not control her PKU, what can happen to baby?
heart defects
microcephaly
devel disab
What are treatment options for PKU?
Low protein diet
Met Formula
Meds to clear toxins: Sapropterin, Palynziq
What is the cause of Tyrosinemia Type 1?
FAH
body cannot produce tyrosine, so then succinylacetone accumulates
What organ is heavily impacted in Tyrosinemia Type 1?
Liver
(FAH)
How can we test for Tyrosinemia Type 1?
(FAH)
Plasma amino acids (tyrosine)
Succinylacetone
How can we treat Tyrosinemia Type 1?
Low pro diet
Met form
Clear toxins - Nitisinone
What is the cause of Alkaptonuria?
HGD
Cannot break down HomoGentisic Acid —> issues over time
What are the main effects of Alkaptonuria?
HGD
dark, melanon-like pigment binds to cartilage and connective tissue —> onchirnosis
dark urine
Builds up in joints –> arthritis, esp spine + larger joints
How can we treat Alkaptonuria?
(HGD)
ONLY: Meds for clearance for toxins - Nitisinone
(same as for Tyrosinemia bc in same pathway)
What is the cause of MSUD?
BCKDHA, BCKDHB, DBT
cannot break down branched chain amino acids
What complications does MSUD lead to?
(BCKDHA, BCKDHB, DBT)
Leucine causes brain swelling that can lead to coma
Can lead to death
What treatment is available for MSUD?
(BCKDHA, BCKDHB, DBT) (Aminoacidopathies)
ONLY low protein diet + met formula
What meds can we use for MSUD?
BCKDHA, BCKDHB, DBT (Aminoacidopathy)
NONE!
What causes Non-Ketotic Hyperglycinemia?
AMT, GLDC, GCSH (Aminoacidopathy)
cannot break down glycine
What complications arise from Non-Ketotic Hyperglycinemia?
AMT, GLDC, GCSH (Aminoacidopathy)
glycine gets into the blood and brain –> terrible seizures/intractable epilepsy + Profound cog disability
How can we limit precursors for Non-Ketotic Hyperglycinemia?
AMT, GLDC, GCSH (Aminoacidopathy)
We cannot bc bods produce much more glycine than what we get from food
How can we treat Non-Ketotic Hyperglycinemia?
AMT, GLDC, GCSH (Aminoacidopathy)
ONLY meds to clear glycins: Sodium Benzoate or Dextromethorphan
NO way to limit precursors
What is the cause of homocystinuria?
CBS - Aminoacidopathy
cannot break down methionine; toxin homocystein builds up
What complications arise from Homocystinuria?
CBS - Aminoacidopathy
results in a body that looks like Marfan, but recurrent strokes (usu adulthood)
How can we treat Homocystinuria?
CBS - Aminoacidopathy
Low protein diet + Met form
Clear toxins w betaine or Vit B6
What is the cause of Glutaric Aciduria Type 1?
GCDH - Aminoacidopathy
cannot break down lysine and tryptophan; toxin glutaric acid builds up
What are main complications of Glutaric Aciduria Type 1?
GCDH Aminoacidopathy
infants can have sudden and unexpected stroke in basal ganglia (pt that controls movement); debilitating movement disorder post stroke
if childhood w/o stroke –> pretty healthy lives w/o stroke risk
How can we treat Glutaric Aciduria Type 1?
Low pro diet + met formula
Clear toxins w Carnitine
Out of these aminoacidopathies:
PKU
Tyro Type 1
Alkaptonuria
MSUD
Non-Ket Hyperglycinemia
Homocystinuria
Glutaric Aciduria Type 1
Which ones can we test for using urine organic acids?
Alkaptonuria
Glutaric Aciduria Type 1
(so ONLY ones w Uria)
Out of these aminoacidopathies:
PKU
Tyro Type 1
Alkaptonuria
MSUD
Non-Ket Hyperglycinemia
Homocystinuria
Glutaric Aciduria Type 1
Which can we NOT limit precursors for?
Alkaptonuria (no benefit shown)
Non-Ketotic Hyperglycinemia (glycine made in body)
Out of these Aminoacidopathies:
PKU
Tyro Type 1
Alkaptonuria
MSUD
Non-Ket Hyperglycinemia
Homocystinuria
Glutaric Aciduria Type 1
Which has NO way to clear toxins by meds?
MSUD
What causes Galactosemia (Carb Disorder)
GALT
cannot break down galactose (milk sugar)
What complications can arise from Glactosemia?
GALT - Carb Disorder
Speech delays, brain damage, jaundice, enlarged kidney, kidney damage, and more
infection E. Coli Sepsis
How can we test for Galactosemia?
GALT enzyme testing
Gal-1-p
Urine galactitol
How can we treat Galactosemia?
GALT
limit precurosor - no galactose
What causes Hered Fructose Intolerance?
ALDOB
cannot break down Fruc-1-phosphate
What complications arise form Hered Fruc Intol?
ALDOB
- Hypoglycemia
- toxic effect on liver, kidney, SI
nausea, vomiting, kidney failure, low Phosphate, FTT, and more
How can we treat Hered Fruc Intoler?
ONLY limit precursors - so no fruits and no sucrose
How can we test for Hered Fruc Intol?
ONLY molecular testing
Bio testing would be too dangerous bc would have to give the toxin
What causes Wilson Disease?
Metal disorder - ATP7B
accumulation of copper in the tissues
What complications arise from Wilson disease?
ATP7B (metal disorders)
Kayser-Fleischer ring (around iris)
Liver failure
Personality disorders like psychosis or movement disorder
How can you test for Wilson disease?
ATP7B
DEC Serum copper
DEC serum ceroluplasmin
INC urin copper (bc accum in tissues)
How can we treat Wilson disease?
ATP7B
limit pre - no high copper foods
clear toxins - chelators (penicillamine), Zinc
What is the cause of Menkes disease?
X-linked; ATP7B (same gene as Wilson, but this is dif) - Metal disorders
defective copper uptake in the intestines
How can we test for Menkes disease?
ATP7B
DEC Serum copper
DEC serum ceroluplasmin
INC urin copper (bc accum in tissues)
What complications arise from Menkes disease?
ATP7B (X-linked)
healthy until 2y, then regression
hypotonia, seizures, FTT, skin laxity
kinky hair
What treatment options are available for Menkes disease?
ATP7B (X-linked)
give copper
NO meds out there
Carrier freq for PKU
1/58
Which of these can lead to problems of myelination ofo the white matter?
PKU —> ID due to this (Aminoacidoapthy)
Which of these can lead to problems w decreased pigmentation?
PKU —> bc melanin is synth from tyrosine
Organic Acid Disorders are severe and typically ?
difficult to treat
(Methylmalonic Acidemia
Propionic Acidemia
Isovaleric Acidemia)
If you think about Amino acids, if you remove the amine group,you end up w a ?
Organic acid!
Methylmalonic Acidemia
Propionic Acidemia
Isovaleric Acidemia
When methylmalonic acid accumulates when it cannot be converted to Succinyl CoA…we have what resulting?
Organic Acid Disorder! Methylmalonic Acidemia
it lowers the acidity of body pH to ~6.9 which is NOT sustainable
Why do those with Methylmalonic Acidemia become pancytopenic?
this means they have low WBC, RBC, and platelet counts
this is bc Methylmalonic Acid SUPPRESSES the bone marrow
it ALSO SUPPRESSES the urea cycle, so elevated ammonia
Methylmalonic Acidemia suppresses ? and ?
Bone marrow AND urea cycle
–> pancytopenia + elev ammonia
Which Organic Acid detects elevated 3C?
Methylmalonic Acidemia
Which organic acid disorder detects elevated 5C?
Isovaleric Acidemia
With Urea Cycle Disorders, we have amino acids that naturally have a Nitrogen group. They are metabolized, then what?
nitrogen = released
Excess nitrogen = converted to ammonia (toxic compound)
urea cycle = pathway by which urea is produced to DETOX the body from excess ammonia
Of these Urea Cycle Disoders:
Carbamyl Phosphate Synthetase (CPS) Deficiency
N-AcetylGlutamate (NAGS)Deficiency
Ornithine Transcarbamylase (OTC)Deficiency
Citrullinemia
Arginnosuccinic Aciduria (ASA)
Arginase Deficiency
Which can be dx on NBS?
ASA and Citrullinemia
