Metabolism/NBS/MNT

Question 1

what three main questions should you ask about substrates?

Answer 1

what’s the molecule?
what are we consuming to get it?
how’s it being stored?

Question 2

how are excess carbs stored? what happens to them when stores are full?

Answer 2

glycogen in liver and muscle

converted to fatty acids

Question 3

what happens to excess amino acids?

Answer 3

converted to glucose and fatty acids

Question 4

when does the body enter fasting?

Answer 4

about 1 hour after eating

Question 5

what are the three processes that occur during fasting? when? what happens?

Answer 5

1) glycogenolysis (1-4 hours), glycogen -> glucose
2) gluconeogenesis (3-12 hours), AA -> glucose
3) fatty acid oxidation/ketogenesis (10+ hours), fatty acids -> ketones

Question 6

what are the body’s main energy users?

Answer 6

brain and muscle

Question 7

What does the brain prefer as energy?

Answer 7

glucose, can use ketones in periods of starvation

Question 8

What roles does the liver play in metabolism?

Answer 8

maintain blood glucose levels, produces enzymes for clotting, and facilitates the creation an recycling of bilirubin

Question 9

What happens if the lysosome enzymes don’t work properly? how can these occur?

Answer 9

massive buildup/storage of material causes them to swell and burst

deficient activity of a single lysosome enzymes, failure of enzymes to localize to lysosome, defect on transport of compounds out of lysosome

Question 10

what are some of the functions of peroxisomes?

Answer 10

produce hydrogen peroxide, play a role in beta-oxidation of VLCFAs

Question 11

what are the common mechanisms of inborn errors of metabolism? what typically causes these?

Answer 11

toxic accumulation of subtances

reduction of normal compounds

usually single gene disorders

Question 12

what are the characteristics of IEMs? how can they be treated?

Answer 12

roughly 1/2 identified outside of neonatal period

most are AR (other types exist)

treat: dietary, oral tx, infusions

Question 13

What happens in GALT deficiency?

Answer 13

missing GALT enzyme -> increased Gal-1-P -> presents symptoms of galactosemia

Question 14

what types of things can occur if there’s an error in a metabolic pathway?

Answer 14

shunting of accumulated substrates on other pathways, accumulation of toxic substrates/products, missing cofactor or enzyme, deficient products of missing enzymes

Question 15

what type of disease has an early onset, severe if untreated, and progressive? i.e PKU

Answer 15

acute disease

Question 16

what type of disease may occur later in life, can live long time w/o treatment, and progressive?

Answer 16

late-onset

Question 17

what types of mutations often cause IEMs?

Answer 17

LoF

Question 18

what are some of the effects of mutations causing IEMs?

Answer 18

reduce activity of an enzyme, reduce or lessen effectiveness of cofactors or activators for the enzyme, produce defective transportation of compounds in the body

Question 19

how can we treat IEMs?

Answer 19

limit substrate and precursors (diet/substrate reduction therapy), process toxic products through alternative pathways, supplement cofactors or provide missing enzyme, supplement products or downstream products, chaperone therapy, intrathecal therapy

Question 20

How might an IEM present in an infant?

Answer 20

vomiting, seizures, ataxia, lethargy, coma,

dysmorphic features

skeletal abn, poor feeding, FTT (very common)

dilated or hypertrophic cardiomyopathy, hepatosplenomegaly, jaundice, and liver dysfunction

DD, hypotonia or hypertonia, visual and auditory disturbances

Question 21

How might an IEM present in an older child or adult?

Answer 21

various levels of LD,DD,ID; autism
exercise intolerance, muscle weakness (can be progressive), behavioral disturbances, ataxia, anxiety/panic attacks, seizures

Question 22

what to look for/ask about in pt Hx for IEM?

Answer 22

onset of symptoms w/ change in diet and unusual dietary preference/aversion

decompensation out of proportion to what would be expected from infection

similar findings of unexplained neonatal or sudden infant death in siblings or materanl male relatives

Hx of deterioration after intial period of good health

infants and young children may have hx of recurrent episodes of vomiting, ataxia, seizures, lethargy, coma, etc.

poor feeding, FTT, DD, may not reach milestones

Question 23

what’s the normal range of glucose in the blood? what level is hypo?

Answer 23

70-140 mg/dl

<50 in children
<55 in adults

Question 24

what can the body do if enough glucose isn’t present?

Answer 24

other food sources: FAs, ketone production and oxidation, metabolism of lactate

Question 25

What should you think of if hypoglycemia is primary?

Answer 25

carb metabolism (GSD I), fat metabolism

Question 26

What should you think of if hypoglycemia is secondary?

Answer 26

disorders of protein metabolism or mito

Question 27

how is NH4 (ammonia) typically removed from the body? what is considered elevated? what happens?

Answer 27

by the liver and excreted in urine >80 disrupts ATP production

Question 28

what symptoms often result from hyperammonemia?

Answer 28

neurological symptoms, significant is seen in a limited # of IEMs

Question 29

what should you suspect if you see 10-100x ammonia levels? 2-3x?

Answer 29

10-100: urea cycle defects | 2-3x: mito or protein metabolism issues

Question 30

What is respiratory alkalosis? acidosis? metabolic alkalosis? acidosis?

Answer 30

1) caused by excessive loss of CO2 (hyperventilation) 2) abn CO2 retention (hypoventilation) 3) reduction of plasma H+ - most commonly from vomiting, ingestion of alkaline drugs 4) net gain of H+ or loss of bicarb -> severe diarrhea, diabetes, strenous exercise, and severe renal failure

Question 31

what is the anion gap? normal?

Answer 31

diff btwn major cations and major measured anions | less than or equal to 16*

Question 32

what can cause an increase in plasma lactate?

Answer 32

increased pyruvate production or decreased pyruvate consumption/oxidation

Question 33

what should you expect if hyperlacticacidemia is primary?

Answer 33

carb metabolism or mito disease

Question 34

what should you expect if hyperlacticacidemia is secondary?

Answer 34

protein or fat metabolism

Question 35

how does ketoacidosis occur?

Answer 35

defects in keton utilization or increased ketone production - typically secondary

Question 36

What does CK indicate? what types of conditions can it point to?

Answer 36

muscle breakdown or injury mito, some LSDs

Question 37

tea colored urine can be a sign of:

Answer 37

rhabdomyolysis

Question 38

what purpose do carnitines serve?

Answer 38

shuffle fatty acids across mito membrane to undergo beta-oxidation

Question 39

If you have galactosemia, you are deficient in: _____. Inheritance? enzyme function?

Answer 39

GALT enzyme Autosomal recessive 5% or less enzyme function

Question 40

what condition is related to classic galactosemia, more frequent, and is known for it Duarte variant? level of enzyme activity? symptoms?

Answer 40

partial transferase deficiency 10-50% enzyme activity usually asymptomatic

Question 41

How is galactosemia detected with NBS? Confirmation? Is there mutation sequencing?

Answer 41

abn high level so fGal-1-P confirmed with GALT classic panel testing looks for 6 mutations (seq also available)

Question 42

what are some of the features of galactosemia?

Answer 42

feeding problems, vomiting, diarrhea, FTT, hypoglycemia, liver failure/jaundica, bleeding, sepsis, females @ increase risk foo premature ovarian failure, DD/ID, cataracts, delayed growth, speech apraxia

Question 43

how can we treat galactosemia?

Answer 43

dietary intervatnion lactose-free formula calcium supplementation

Question 44

the types of Glycogen storage disease can be broken into 2 groups:

Answer 44

hepatic (GSD1 and III) - enlarged liver muscular (GSD II and V)

Question 45

Classic PKU and maternal PKU are both examples of _______ deficiency. This is an example of a defect in _________ metabolism.

Answer 45

PAH, protein

Question 46

untreated classic PKU can present with:

Answer 46

seizures, severe or profound ID, microcephaly, behavioral problems, very light skin and hair

Question 47

those with PKU may have _______ smelling urine.

Answer 47

mousy

Question 48

how can we treat PAH deficiency? what other amino acid becomes essential (needed from diet)?

Answer 48

``` PKU diet (limit Phe) avoid meat, fish, eggs (high protein) use Phe-free formula as supplement ``` tyrosine because the body cannot make it from Phe

Question 49

What is tthe purpose of the urea cycle? how might you detect UC defects?

Answer 49

rid body of waste nitrogen elevated levels of ammonia in blood

Question 50

how can we treat UC defects?

Answer 50

restrict substrate or precursor provide or supp. deficient enzyme increase alt pathway use supplement products

Question 51

Maple syrup urine disease, isovaleric aciduria, 3MCC deficiency, MMA, Canavan disease, and biotinidase deficiency are all examples of:

Answer 51

organic acidurias

Question 52

How are fatty acids released in the body?

Answer 52

lipoprotein lipase and hepatic lipase cleaving triglycerides

Question 53

VLCAD, LCHAD, TFP, MCAD, SCAD, SCHAD are all examples of:

Answer 53

Fatty acid oxidation defects

Question 54

If you are deficient in MCAD enzyme and have a 985A>G, K304E mutation then you have:

Answer 54

MCAD

Question 55

what anaylte trends are seen in MCAD?

Answer 55

low plasma carnitine, high medium-chain acylcarnitines

Question 56

how can we treat MCAD?

Answer 56

modify infant diet (30% fats) supplement carnitine as needed avoid prolonged fasts

Question 57

What is the clinical relevance of fatty acid oxidation defects?

Answer 57

oftn cause infant or childhood death following minor illness with fasting affecting multiple sibs in a family tx available and highly effective for some

Question 58

what condition set the standard for NBS?

Answer 58

PKU

Question 59

what are the criteria for conditions on NBS?

Answer 59

severe consequences if not treated soon after birth simple and inexpensive biochemical test treatable and is available and effective

Question 60

when do we screen infants for IEMs? why? core panel screens for how many conditions?

Answer 60

24-48 hours after birth (at least one meal) don't want to screen in a fasting state 35+

Question 61

Tandem Mass Spec for NBS has a relatively high FP rate...why?

Answer 61

so we don't miss as many as possible

Question 62

what are the goals of medical nutrition therapy?

Answer 62

promote healthy brain function and healthy physical growth/development

Question 63

whats' the major energy difference between simple and complex carbs?

Answer 63

simple -> quick source | complex -> longer to break down

Question 64

what's the goal for MNT for carb metabolism defects?

Answer 64

avoid prolonged fasting, restrict offending sugar, prevent hypoglycemia

Question 65

In GSD Type 1a, pts can store glycogen but not break it down, how might we treat this with MNT?

Answer 65

high protein, low carb use sucrose and lactose free formula consume complex carbs (cornstarch) use nighttime feedings to prevent fasting

Question 66

generally those with protein metabolism disorders are not allowed: ... what are they allowed?

Answer 66

most high protein foods high carb food in high amounts

Question 67

What fatty acids must come our diets?

Answer 67

Omega 6 and 3