Metabolic Flashcards
What basic bloodwork do you do for metabolic conditions?
Gas Lytes Glucose Ammonia Lactate
note: hamilton 3 acute test: plasma a.a., plasma acylcarnitine, urine organic acid
Metabolic disorder= Lactic Metabolic acidosis (AG acid) + Normal or high ammonia. What type of metabolic dx?
Organic acidemia (proprionic acidemia, methylmalonic acidemia or glutaric acidemia)
++ Ammonia and normal gas. What type of metabolic dx?
Urea cycle defect (OTC, Citriulinemia, Arginosuccinic acidemia)
Normal ammonia
Normal AG.
What type of metabolic dx?
Aminoacidopathy (MSUD, PKU, Homocystinuria) or Galactosemia
How can you tell the diff between organic academia vs. urea cycle defect vs. amino acidopathy:
Organic Acid:
= AG Met Acid
Urea Cycle
= HI ammonia
Normal AG
A.A. or Galact
= Normal everything.
How do you tx an organic acidemia?
Acute: STOP Protein intake IV Dextrose 10% with NaCl Correct metabolic acidosis IV lipid emulsion \+/- Dialysis
Longterm: Low protein diet from food (w/ food that don’t have certain a.a) BUT min. protein for growth
T or F: there are CBC changes with organic acidemia?
True. Nelson's talks about this re: proprionic acidemia - neutropenia - thrombocytopenia - pancytopenia
… due to bone marrow suppression
what is the diff in urea cycle versus organic academia BW?
Organic academia:
AG + severe metabolic acidosis
Both can have ammonia +
Urea cycle:
normal AG. normal or alkalotic pH +/- Tachypnea w/ resp alkalosis. ICP.
What is galactosemia?
Deficiency in galactose- 1 - phosphate uridyl transferase
When does galactosemia usually present?
DOL 3-7 (once exposure to lactose containing milk)
CC: jaundice, big liver, vomit, low BG, FTT, sz, lethargy, nuclear cataracts
What type of sepsis are kids with galactosemia at higher risk for?
E coli.
Neonatal Sepsis
What is screen and the dx test for galactosemia?
Prelim dx
= reducing substance in urine
Dx
= RBC enzyme assay looking for galactose 1 phosphate uridyl transferase deficiency
= DNA mutation in GALT gene
How do you tx galactosemia?
Non lactose containing milk substitute
= casein hydrolysate, soy bean based formula
+ Ca2+ supp
All long term risk are reversed with galactosemia tx?
False.
Still long term risk= ovarian failure, lower bone mineral density, DD, LD.
BUT you do reverse liver, renal and growth issue and cataracts
10 d with FTT, jaundice, hepatomegaly. BCX E coli. What disorder may child have? What test to confirm?
Galactosemia
Confirm:
- erythrocyte GALT (galactose-1-phosphate-uridyl transferase activity) deficiency
- DNA testing for GALT gene mutation
Hyperammonia child. List 3 steps in management:
“Hydrate+ Substrate- Med- Dialysis”
STOP PROTEIN
- Rehydrate
= stop protein catabolism in tissue - Give Substrate=
Fluid, Fat, Lytes
= D10W, NaCL, lipids
w/ min. amt of essential a.a. - Priming doses then infusion of: “ABP”
* > Arginine HCL
* > Na benzoate/phenylacetat (ammonia scavengers) - dialysis if tx above fails
T or F: VPA is drug of choice in kids with hyperammonemia if seizing:
False.
- Increase ammonia
- decrease urea cycle f’n
= DO NOT USE.
Baby with hypoglycaemia. No ketones. 2 DDX:
- Hyperinsulinism
- F.a. Oxidation Defect (high f.a. on BW)
- Other (panhypopit, SGA, birth asphyxia)
3 day old. Lethargic. Worsening LOC. Coma. Intracranial HTN. Resp Alkalosis. Dx?
Urea cycle defect
Name one organic acidemia:
Methamelonic Acidemia, proprionic acidemia, glutaric acidemia (the hard to Dx one with macrocephaly and mvmt d/o when unwell, subdural hematoma)
Previously Well child, presents with weakness, lethargy, coma Classic Lab Findings: Metabolic Acidosis with high AG Mild - Moderate Ammonia elevation High Ketones
Name one urea cycle defect:
Ornithine Transcarbamylase deficiency (OTC)
Citrulinemia
Arginosuccinic aciduria
Name one aminoacidopathy:
- Maple Syrup Urine Disease
- PKU
- Homocystinuria (Marfanoid-like, thrombosis problems)
IEM: Musty or mousy order.
PKU = Phenylketonuria
Autosomal Recessive Normal Ammonia. Normal pH. Presentation : Fair skin and hair Eczema Light Sensitivity Hair Loss Untreated - Mousy Odor, Epilepsy, Eye abnormalities (hypopigmentation), SEVERE ID
IEM: Maple Syrup smell
Maple Syrup Urine Disease
Autosomal Recessive
Presentation: Baby 3-5 days with poor feeding, irregular respirations, hard to arouse, coma, death
What do you do if your newborn screen is (+) for PKU?
Order quantitive BLOOD phenylalanine level.
Don’t repeat screen; CONFIRM!
Phenylketonuria is inherited?
AR.
Carrier are unaffected.
What type of inborn error of metabolism is PKU?
Aminoacidopathy.
Meaning ammonia, pH, AG all normal.
List three traits of PKU:
- Fair skin + blue eyes.
- Microcephaly
- Musty odour (breath, skin odour)
- Growth retardation
- Intellectual impairment.
- Eczema
- Light sensitivity
- Hair loss
How do you confirm dx of PKU?
Quantitive Blood phenylalanine level.
If > 120= Dx
OR altered phenylalanine/ tyrosine ratio in untreated state.
How do you treat PKU?
Phenylalanine limited diet (PKU formula, diet modification, avoid aspartame)
+ Supplement tyrosine
List 3 complications of maternal PKU:
- IUGR
- Intellectual impairment.
- Developmental delay
- Microcephaly
- CHD
Screening BW for kid in shock with suspicion for IEM?
- Lactate, ammonia, VBG, glucose, electrolytes
- Acetylcarnitine profile help dx f.a. oxidation defect
6 mo. old w/ DD brought in shock. Now stable. Help with dx via:
a. CT
b. lactate, carnitine, ammonia
c. serum organic acid
d. urine a.a.
Lactate
Carnitine
Ammonia
Which protein metabolism in IEM present as shock? What else is on DDX?
Organic Academia (proprionic, glutaric, methylmalonic, etc) - High AG metabolic acidosis.
DDX: urea cycle defect, aminoacidopathy, galactosemia
DDX: infection, trauma, CNS anomaly
What is the most common f.a. oxidation disorder?
MCAD Deficiency
= Medium chain acyl-CoA dehydrogenase deficiency
T or F: MCAD typically has non ketotic hypoglycaemia AND no acidosis.
true.
Abetalipoproteinemia causes all EXCEPT:
- ataxia
- hyperlipidemia
- acanthocytosis
- retinitis pigments
- diarrhea + FTT
NO Hyperlipid.
—> think A … (as in missing)… lipo…..
Abetalipoproteinemia:
- severe fat malabsorption
- can’t make lipoprotein
- intestinal bx show ++ lipid in enterocyte (fat stuck in wall)
- low cholesterol, TG, ADEK
- acanthocytosis (Spiked RBC smear), ataxia, loss of DTR (secondary to Vitamin E deficiency), night blindness (pigmented retinopathy)
Distal RTA. How do you remember it?
D1stal= Type 1= H+ is one letter
= collecting duct can’t excrete H+
= high urine pH
= low K, Ca2+ kidney stones
versus. Proximal= type 2= bicarb reabsorption lacking
= link w/ low phosphate rickets
AG calculation:
(Na+) - (Cl-) - (HCO3-)
Normal: 8-12
Xray with VERY WHITE bones. Think of marble bones dx. Name?
OsteoPETROSIS
= bone do not reabsorb (osteoclast issue) / remodel
ANEMIA with extra medullary hematopoiesis in liver and spleen = hepatosplenomegaly
Optic and facial nerve problems b/c bone no change = deafness and blindness
Can #
6 mo. old pale. irritable. XR show very white bone. Dx?
Osteopetrosis
Cardiomegaly and hypoglycaemia. Like etiology:
- cardiac lesion
- sepsis
- IEM
Inborn error of metabolism (IEM)
Think Pompe!
What is Pompe disease?
Glycogen storage disease.
- AR
Classic ppt of Pompe:
Poor Tone Feeding Issue Big Liver Hypertrophic cardiomyopathy High CK NO hypoglycaemia, no aciduria.
Lethargic. Poor feed. Big liver. Normal ammonia, pH, lactate. Likely dx?
- Maple Syrup
- Propionic acidemia
- Urea cycle defect
- Galactosemia
Galactosemia
- galactose-1-phosphate uridyltransferase
- jaundice
- hepatomegaly
- low BG
- lethargic, sz, irritable
- coagulopathy
- normal BW except liver problem, ++ plasma a.a.
- dx via RBC GALT deficient or gene mutation
Tx: non lactose containing milk substitute
Maple Syrup= Aminoacidopathy
- poor feed, lethargic, athetoid (fence, cycling), spastic, sz
- N pH + amm but ketoaciduria w/ high plasma a.a.
- no hepatomegaly noted
Propionic acid= organic acid= high ammonia + AG met acid
Urea cycle: high hmm + N pH or resp alk
T or F: decreased LOC (encephalopathy) prior to focal neuro deficit or feature suggest inborn error of metabolism.
True.
T or F: if suspect IEM and unsure of definitive dx it is fair game to give thiamine to prevent further sequelae?
False.
Give cofactors that may be missing in IEM
> Carnitine (organic academia, f.a., caritine def)
> B12 (cobalamin; organic acid)
> B6 (pyridoxine; for neo sz)
> Biotin (for neo recurrent sz for carboxylase def)
Which coFactors can you give to prevent sequelae while waiting IEM dx?
- Carnitine
- B12
- B6 (neo sz)
- Biotine (neo sz)
T or F: liver dysfunction is long term complication of MCAD (lipid metabolism defect).
True.
Lang delay and inferior ectopia lentis. Dx?
Homocystinuria
“Downward IQ= Downward Lens”
How do you dx homocystinuria?
Plasma a.a.
= elevated methionine or homocysteine in body fluid (urine or blood)
What is downward lens= down IQ. Dx?
Homocystinuria.
Versus marfan
= upward dislocation= normal IQ.
List 3 diff between marfan + homocysteinuria.
Marfan: AD
Homo: AR
Marfan: upward lens
Homo: downward (inferior ectopia lentis)
Marfan: normal IQ
Homo: low
Marfan: joint laxity
Homo: rigid
Marfan: Ao root dilation.
Homo: thromboembolism predisposition
Homo: tx w/ vitamin B6
How do you decide which diseases to create screening test?
- Disease (natural hx allow tx, cure or halt complications if caught early)
- Test known
- Treatment (effective, $)
- Societal implications
Which is best clue to probable genetic dx?
- sibling died of unknown cause
- fhx dementia
- child adopted
- hx cancer in distant relatives
- parents first cousin
Sibling died of unknown cause > consanguinity.
What inheritance pattern suggest mitochondrial disease?
Maternal inherit
i.e. mom and her mom have hearing loss + DM
NOTE: Boy + Girl affected
But boy can’t pass it on.
T or F: lactate is usually UP in mitochondrial dx?
True
T or F: poor response to glucagon hallmark of hyperinsulinemia?
False.
Exaggerated response key (i.e. 1.8 to 4)
Workup for DD?
- Chromosomal Microarray
- Fragile X
- Hearing
- Metabolic: Lytes, gas, ammonia, BG, lactate, CK, LFT, CBC, a.a. serum, urine organic acid, acylcarnitine profile
- MRI if macro, microcephaly or neuro signs
Metabolic crisis approach:
> Rehydrate
- ABC, resus, no dehydration
> Substrate
- 2X D10NS + 20K
- protein restrict
- caloric restriction
- megavitamins
> Meds
- if known (ammonia ABP- arginine, Na benzoate, Na phenylactate)
- Carnitine
- B12 (met acidosis)
- B6 or Biotin if neo sz
> Dialysis
7 mon. VLCAD. Gastro. Mild dehydration. What do you start?
D10NS x 1.5 maintenance
** never give lipids to f.a. oxidation disorder.
7 mon. VLCAD. What BW:
Lytes Glucose BUN Cr **CK (Rhabdo)
2 y.o. developmental delay. ? liver enlargement. Which investigations FIRST:
- Urine MPS
- plasma MPS screen
- Microarray
- Plasma a.a
- Plasma acylcarnitine profile.
If that’s normal- 2nd test?
Microarray
Urine mucopolysaccharide screen
= MPS= Enzyme replacement therapy
+ Bone marrow/stem cell transplant
MCAD. Vomit and diarrhea. Next?
Stat BG
Start IV fluid w/ D10W
