Inborn Errors of Metabolism - Proteins Flashcards

(32 cards)

1
Q

Two main ways to test for PKU?

A

Guthrie heel blood spot

Tandem mass spec

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2
Q

Bayesian reasoning and pretest probability

A

Even with a very good test, post-test probability is still low if the pre-test probability is low

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3
Q

PKU due to

A

Phenylalanine hydroxylase deficiency

AR

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4
Q

Rare cause of PKU

A

Disorder of Tetrahydrobiopterin (BH4) cofactor

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5
Q

4 main manifestations of untreated PKU

A

Intellectual disability
Hypopigmentation
Eczema
Hypomyelination on brain MRI

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6
Q

Treatment of PKU

A

Dietary restriction of protein

supplement all non-Phe aa

life long

IF residual enzymatic acitivity can give Sapropterin - suuplemental BH4 cofactor

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7
Q

PKU and IQ

A

IQ is directly related to the age of initiation of therapy and the Phe levels achieved in childhood

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8
Q

Sapropterin

A

Treatment (BH4) for PKU with residual enzymatic activity

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9
Q

Maternal PKU

A

Phe is teratogenic

Should limit Phe well before conception and through gestation

Infants born to mother with unctontrolled PKU have growth restriction, microcephaly, IQ, and heart malformations

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10
Q

MSUD cause

A

deficiency in branched chain ketoacid dehydrogenase complex (BCKAD)

MOST manifestations are due to leucine accumulating in the brain

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11
Q

MSUD neonatal presentation

A

Irritable and poor feeding at 48 hours

Lethargy, opisthotonus, apnea

Cerebral edema, encephalopathy

REVERSIBLE with treatmetn

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12
Q

MSUD diagnostic findings

A

elevation of luecine

presence of allo-isoleucine

urine ketones in neonate

Low BCKAD activity

Can genetically sequence for 4 common genes

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13
Q

MSUD unique deficiency

A

DLD

assess lactate and alpha-ketoglutarate levels to ensure the child does not have combined enzyme deficiencies (DLD)

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14
Q

MSUD acute decompensation treatment

A

ABCD
remove offending agent (Dietary protein) supplement deficiencies

provide calories for anabolism to prevent mobilization of endogenous proteins (dextrose IVF/IV)

Consider dialysis in some

Slowly reintroduce proteins

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15
Q

MSUD chronic management

A

Trial thiamine supplement

Limit dietary protein

Leucine free formula

monitor isoluecine and valine levels

consider liver transplant (because they can give theirs)

Leucine is likely teratogen

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16
Q

Tyrosinemia Type I (hepatorenal type)

characteristic presentation?

A

acute liver failure in infancy
later hepatocellular carcinoma

hyperbilirubinemia / jaundice / ascites / all those things that go along with having a fucked up liver

rickets

acute neurological crisis with abdominal pain and neuropathy due to secondary porphyria

17
Q

Tyrosinemia type I

cause

A

Results from fumarylacetoacetate hydrolase deficiency

18
Q

Tyrosinemia type I diagnostic metabolite

A

succinylacetone in urine

19
Q

Tyrosinemia type I management

A

Use medication (nitisinone - NTBC) to induce a different (milder) disease (Tyrosinemia type III) - Buildup of tyrosine but not subsequent hepatotoxic byproducts

monitor Tyr and Phe levels - tyrosine crystals can form on cornea :(

liver transplant may be necessary - monitor for HCC

20
Q

Tyrosinemia type II (oculo-cutaneous type)

A

Results from 4-hydroxyphenypyruvic acid dehydrogenase deficiency (earlier)

Results in palmoplantar hyperkeratosis and keratitis

causes much higher Tyr
no acute decomp
manage by Tyr and Phe limitation and supplement other aa

21
Q

Homocystinuria

A

Deficiency in cystathionine beta synthase

elevated homocysteine is toxic to skeleton - eye - vasculature

22
Q

Homocystinuria - manifestation if untreated

A

lens dislocation / scoliosis / pectur carinatum / mild DD - marphenoid

elevated thrombotic risk

23
Q

Homocystinuria - sequelae even if treated?

A

osteoperosis and vascular risk

24
Q

Homocystinuria treatment?

A

restrict protein / methionine

folate / vitamin B12 supplementation

Pyridoxine (B6) trial

Betaine - alternative breakdown product

Diminish CV risk - avoid smoking and maybe anticoagulate

25
Acute consequences of hyperammonemia
encephalopathy / seizures / ataxia / visual loss / hallucinations / mania vomiting / anorexia in neonates temperature instability and hyperventilation
26
chronic consequences of hyperammonemia
DD Nausea / FTT / protein avoidance magrainse / anxiety / depression / disinhibition hepatomegaly/ elevated liver enzymes
27
Triggers of hyperammonemic episode?
illness, fever, vomiting, fasting, surgery postpardum, menarche intense exercise dietary protein load medications - valproate / peg asparaginase UTI
28
MOST common urea cycle disorder
OTC deficiency ornithine transcarbamylase deficiency X linked
29
Is there a newborn screen for OTC?
NO
30
OTC diagnosis?
orotic acid low citrulline high glutamine
31
OTC treatment?
ammonia scavengers - sodium phenylacetate - sodium benzoate - cheaper
32
Management of OTC
``` LOW protein diet (lowest of all IEMs) supplemnet citrulline or arginine ammonia scavengers close nut monitor dialysis liver tranplant future gene therapy ```