Peds Board Review - Metabolic Disorders

Front 1

If you see labs with:
- plasma amino acids and urin organic acids
- metabolic acidosis with urine ketones
- increased anion gap
You should think about ______ In born error in metabolims?

Back 1

Amino acid diseases

(Maple syrup urine)

Front 2

If you seelabs with:
- Plasma ammonium
- NO metabolic acidosis
- respiratory alkalosis
You should think about ______ In born error in metabolims?

Back 2

Hyperammonemia

(Ornithine transcarbamylase or OTC deficiency)

Hint 2

- increased glutamine
- mild or no liver dysfxn

Front 3

If you seelabs with:
- plasma amino acids and urin organic acids
- metabolic acidossi with urine ketones
- plasma ammonium
- increased glycine
- abnomral urine organic acids
- increased anion gap
You should think about ______ In born error in metabolims?

Back 3

Organic acid disease

(propionic acidemia)

Front 4

If you seelabs with:
- NBS enzymatic testing
- urine organic acids
- liver enzyme analysis
You should think about ______ In born error in metabolims?

Back 4

Sugar intolerances: galactosemia, fructosuria

Front 5

How are most inborn erros of metabolism inherited?

Back 5

AR >>> X linked
few AD
"newer" mitochondrial

Front 6

When should you suspect an inborn error of metabolism in an infant with acute encephalopathy?

Back 6

** when the encephalopathy occurs without warning and progresses rapidly
** NOT associated with focal neuro deficits
** normal birth, normal pregnancy
- sxs: unexplained seizures, lethargy, coma, hypo/hypertonia

Front 7

How does chronic encephalopathy present?

Back 7

** Slowly progressively symptoms from the build up of toxic metabolites

Front 8

What events will exacerbate energy defect metabolic disorders?

Back 8

** Fasting or illness with increased energy needs can exacerabate the disorder and bring on decompensation

Front 9

If you see a kid with:
- hypoketotic hypoglycemia
- hypotonia
- cardiomyopathy
- SIDS death
You should think about ______

Back 9

Fatty Acid oxidation defects

Front 10

If you see a kid with:
- hepatogmgaly
- hypoglycemia
- lactic acidosis
- FTT
You should think about ______

Back 10

Glycogen storage disease

Front 11

If you see a kid with:
- lactic acidosis
- seizures
- cardiomyoathy
- hypotonia/ muopathy
- +/- hypoglycemia
You should think about ______

Back 11

mitochondrial disorders

Front 12

Name 3-6 Lysosomal storage disease:

Back 12

- Mucopolysaccharidosis (MPS) types I-IX
- Gaucher disease
- Niemann-Picc disease, types A, B, C
- Tay-Sachs disease
- Fabry Disease
- Neuronal ceroid lipofuscinosis

Front 13

Name 3-5 Peroxisomal storage diseases:

(All are AR except one!)

Back 13

- Zellweger syndrome spectrum
- X-linked adrenoleukodystrophy (X-ALD)
- Refsum disease
- Mevalonate kinase
- Rhizomelic chondrodysplasia puctata

Front 14

Name 3-5 intracellular trafficking and processing defect disorders

Back 14

- Menkes disease
- Wilsons disease
- hemochromatosis
- alpha-1-antitrypsin dificiency
- congenital disorders of glycosylation

Front 15

Name 3-5 inborn errors of cholesterol synthesis disorders:

Back 15

- Smith=Lemli-Opitz syndrome
- Hypercholesterolemia, AD
- Apolipoprotein E deficiency
- Tangier disease
- Desmosterolosis

Front 16

What is the most useful test to examine for disorders of amino acid metabolism?

Back 16

BOTH:
** plasma amino acids
** urine organic acids

Front 17

How is PKU inherited?

What is defect and hat does it cause?

Back 17

** AR
** phenylalanine hydroxylase is defective so phenalyalanine cannot be converted to tyrosine
- build up of phenylalanine

Front 18

You see an infact with vomiting, irritability, eczematoid rash, mousy/wolf like/musty odor ---
What do you suspect? what is causing the odor?

Back 18

PKU
Odor: phenylacetic acid in urine

Front 19

What subset of children with hyperphenylalaninemia will present with severe neurological disease, even with dietary treatment that mains normal phenylalanine levels?

Back 19

defect in synthesis or recycling of bioprterin - neuro sxs that progress in spite of dietary tx that maintains norm phenylalanine levels

What is the treatmetnt for those children since dietary restrictions don't work?

Hint 19

Tx phenylalanine restriction and biopterin supplements and biogenic amine precursors such as 5-hydroxytryptophan and dopa

Front 20

In patients with hyperphenylalaninemia, defect in tetrahydrobioterin is also a cofactor for the hydroxylation of tryptophan and tyrosine -- in tern it interferes with synthesis of ____, ____, and ____

Back 20

*Serotonin
* Dopa
* NE

Front 21

What is the clinical presentation of a patient with hyperphenylalaninemia?

Back 21

- Drooling
- posturing
- hypotonia
- spasticity
- psychomotor delay

Front 22

What is tyrosinemia and what is the inheritance pattern of Tyrosemia Type I, II and III?

Back 22

** group of disorders with common theme of ELEVATED tyrosine levels in body fluids
* AR

Front 23

Type I tyrosinemia

Back 23

0 deficiency of fumarylacetoacetate hydroxylase
- accumulation of succinylacetone
- early --> death; some progress slowly
- FTT, hepatomegaly, hepatoblastoma
* NOT MR
- renal tubular acidosis like Faconi, XR like rickets

Front 24

How do you treat liver failure and Faconi syndrome of hepatorenal tyrosemia?

Back 24

** NTBC
- 2-(butri-4-trifuoro-methyl-benzolyl-1, 3-cyclohexanedione

Hint 24

Blocks tyrosine breakdown --> high tyrosine

Front 25

Tyrosinemia Type II

Back 25

- deficiency of tyrosine aminotransferase
- corneal ulders or dendritic keratosis, red papular or keratotic lesions on palms and soles
- 50% MR
- skin and eye lesions due to deposition of tyrosine

Front 26

Tyrosinemia Type III

Back 26

Extremely rare!!!!
- deficiency of 4-hydroxyphenypyruvate dioxygenase
- MR

Front 27

What is Alkaptonuria?

Back 27

** deficiency in homogentisic acid dioxygenase (3rd step in tyrosien metabolism)
- tyrosine NOT elevated
- excretion of dark colored urine

Front 28

What happens to the urine of kids with alkaptonuria?

Back 28

** fresh urine = norm
** sits and alkalinizes -- oxidation of homogentistic acid --> dark-brown/black pigement (?brick dust)

Front 29

What happens to the ears and sclera in adult (30s+) patients with alkaptonuria?

Back 29

deposition of pigment in ears and sclera =
** ochronosis

Front 30

What are the branched-chain amino acids?

Back 30

** Lucine
** Isoleucine
** Valine

How do you dx a defect?

Hint 30

Urine organic acid test
** look for weird urine odor!

Front 31

Describe the sxs of Maple syrup urine disease (MSUD)

Back 31

** CNS disease early in infancy
** Urine (or hair/skin) smells liek maple syrup
- sxs by day 3-5, death 2-4 weeks
- feeding difficulty, irregular resp
- loss of moro
- sz, opisthotonos

Front 32

MSUD

Back 32

** mapple urine
- rapid progression
- defect in oxidative decarboxylation of ketoacids (= sweet smell) formed by catabolis of branched chain AA
- AR

Front 33

How do you Dx MSUD?

Back 33

** Dx: inc amt of leucine, isoleucine and valine in plasma and urine
*** finding alloisoleucine = abnorm AA = DX

Front 34

What metabolic disease can be mistaken for child abuse?

Back 34

Glutaric aciduria type I

What can it cause?

Hint 34

** Subdural hematomas
** retinal hemorrhages

Front 35

What are the lens findings in Marfan syndrome vs homocystinuria??

Back 35

Lenticular subluxation
** downward and medial (low IQ) = homocystineuria
** upward (nomral IQ) = marfan

Front 36

What is the clinical picture of someone with Homocystinura?

Back 36

cystathionine beta-synthase deficiency
** Marfanoid habitus
** DD / MR **
** lens dislocation
** inc riks of thromboembolism in arteries and vins
*** subluxation/dislocation of ocular lense

Front 37

If you see a neonate with intractable seizures (or sz and apnea requiring intub) and h/o hiccups in utero with large amounts of glycine in body fluids what do you think of?

Back 37

Nonketotic hyperglycemia
- AR
- Dx by comparing CSF and plasma glycine levels

Front 38

What molecule is the problem in all urea cycle disorders?

Where does the Urea cycle occur?

Back 38

** AMMONIA (NH₄⁺) is problem
** ususally borken into glycine, glutamine, carbamyl phosphate

periportal hepatocytes (mito) of liver

Front 39

Describe the urea cycle....

Back 39

NH₄⁺ --> Carbamolyl phosphate --> Citrulline --> argininosuccinate --> argine --> urea into urine

Front 40

Name 2-6 urea cycle disorders

What is the inheritance pattern of all except 1?

Back 40

- N-acetyle synthetase deficiency (NAGS deficiency)
- Carbamoly phosphate synthetase I (CPS deficiency)
** Orthine transcarbamolyase deficiency (OTC - most common and X-linked!!)
- Arginosuccinate synthase deficiency (Citrullinemia)
- Arginosuccinate lyase deficiency (argininoscuccinic aciduria)
- Arginase deficiency (argininemia)

** AR except OTC = X-linked

Front 41

At what level of ammonia does grain edema occur? How does hyperammonia present?

Back 41

** 100-200 umol/L
** lethargy, vomiting, confusion ----> coma
*** ammonia and elevated CSF glutamine = toxic

Front 42

if the urea cycle defect is more (proximal or distal), it causes more severe symptoms?

Back 42

** Proximal

CPS and OTC are the worst!

Front 43

You see an infant with elevated ammonia, no liver abnorm, and mild/no ketoacidosis. What defect should you consder?

Back 43

** Urea cycle

** also low BUN and resp alkalosis

Front 44

you see blood gas... respiratory alkalosis what you think of??

Back 44

**** Urea cycle defect!

Front 45

Which urea cycle defect do you think of if you have:
- progressive spastic diplegia/quad
- tremor
- ataxia
- choreathetosis

Back 45

Argininemia

Front 46

Which urea cycle defect do you think of if you have:
- porgressive spastic diplegia/quad
- retinal depigmentation
- chorioretinal thinkking

Back 46

HHH = hyperorthithinemia, hyperammonemia, homocitrullineura = mitorchondrial ornithine transporter ORNT1

Front 47

Which urea cycle defect do you think of if you have:
- interstitaial PNA (d/t pulm alveolar proteinosis
- glomerulonephritis
- osteoporosis
- underlying immune deficiency

Back 47

LPI = Lysinuric protien intolerance = amino acid transporter gene SLC7A7

Front 48

Which urea cycle defect do you think of if you have:
- Trichorrhexis nodosa (node like appearance of fragile hair_
episodic coma

Back 48

Arininosuccinic aciduria

Front 49

What does the citrulline level tell you?

Back 49

** absent/low - d/o proximally - OTC, CPS

How do you differentiate between the two?

Hint 49

** Check Urine orotic acid level
- elevated = OTC
- norm/low = CPS and NAGS

Front 50

Which urea cycle defect is plasma arginiene concentration NOT low??

Back 50

*** argininemia