Inborn error Weisfeld Flashcards

1
Q

PKU

  • Mode of inheritance?
  • Due to?
A

autosomal recessive

PAH deficiency

  • Phenylalanine hydroxylase
  • Phenylalanine cannot be converted to tyrosine (precursor for niacin)
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2
Q

Assay to screen for PKU

A

Guthrie bacterial inhibition assay

- 3mm blood spots (+) if bacterial halo is seen (indicating high PA [ ])

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3
Q

Disease phenotypes can result from:

A
  1. Accumulation of metabolite A
    - precursor toxicity
  2. Overflow to products E or F
    - alternative, potentially toxic metabolites
  3. Reduced formation of metabolite D
    - product deficiency
  4. COmbo of all of the above
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4
Q

Severe levels of Phe
Moderate
Mild/benign

A

severe: >1200
moderate: 600-1200
mild/benign:

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5
Q

Maternal PKU presentation

A

Malformation in infants of mothers with poorly controlled PKU

  1. microcephaly
  2. low birth weight
  3. mental retardation
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6
Q

Long term management of PKU

A

Treatment for life

  1. Restrict PKU, but DO NOT eliminate it
  2. Provide adequate calories, protein, vit, minerals
  3. Maintain nl growth and development
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7
Q

Key management of Inborn Errors of Metabolism (IEM):

- Coma/encephalopathy

A
  1. remove offending agent
    - NPO
    - Stop catabolism
    - dialysis
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8
Q
Name disease:
Newborn
Breast fed female
Poor feeding, progressive lethargy
Mild hypoglycemia
Mild met acidosis
Ketonuria
  • what test can verify your guess
A

MSUD

  • Ketones are not usually detected in newborns
  • DNPH test should be pos
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9
Q

4 subunits can be affected in MSUD

A

E1 a
E1 b
E2
E3

These lead to a branched chain ketoacid dehydrogenase (BCKD) deficiency

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10
Q

Mode of inheritance of MSUD

A

Auto recessive

Deficiency in BCKD

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11
Q

Severe neonatal
Acute intermittent
Subacute chronic
presentations of MSUD

A

Severe neonatal

  • few abnormalities on routine lab tests
  • Maple syrup odor in urine

Acute intermit:

  • late onset
  • ataxia
  • Ketoacidotic coma
  • AA and ketoacid can be nl btwn attacks

Subacute chronic

  • hypotonia and developmental delay
  • failure to thrive
  • spastic paraplegia
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12
Q

ACUTE tx of MSUD

A
  1. Eliminate dietary protein intake
  2. Supplement valine and isoleucine
  3. Provide adequate non-protein E source and aa that are NOT BCAA
  4. Avoid hypotonic fluids
  5. Treat cerebral edema
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13
Q

CHRONIC tx of MSUD

A
  1. Protein restricted diet supplemented with BCAA free medical foods
    (MSUD coolers)
  2. Leucine intake 400-600 in severe neonatal
    600-800 after adolescence
  3. Supplement valine and isoleucine
  4. Thiamine supplementation in some cases of E2 subunit def.
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14
Q

Tyrosinemia Type I

  • cause
  • What builds u?
A

FAH deficiency (downstream of Tyrosine)

  • Tyr –> FAA cannot ultimately be broken into fumarate and acetoacetate
  • Succinylacetoacetate forms due to alt path
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15
Q

Tyrosinemia Type 1 presentation
Early infancy
Late infancy
Any age

A
Early infancy (1-6 mo)
- Liver disease (hepatic failure, cholestatic jaundice or cirrhosis with renal tubulopathy)

Late infancy:
- Rickets due to renal tubulopathy (Fanconi syndrome) with no liver failure
(leaky kidneys)

Any age
- Porphyria like attack

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16
Q

Tx of Tyrosinemia type 1:

A
  1. NTBC
    - inhibits point in Tyrosine catabolic pathway
    - -> Increases plasma Tyr
    - -> Decreases production of FAA and succinylacetone
  2. Phe and Tyr restriction (thanx to step 1)
  3. Liver transplant if hepatocellular carinoma develops
17
Q

If pts with Tyrosinemia adhere to their NTBE drug tx, but not their Phe and Tyr restriction, what can result?

A

Plantar keratosis

- groadie yellow scaling on palms and soles

18
Q

Classical untreated Homocystinuria sx

A
  1. skeletal malformations
    - marfanoid habitus
    - osteoporosis
    - scoliosis
  2. Recurrent thromboembolism
  3. Eye abnormalities
  4. developmental disability and neuropsychiatric sx
    * most common in B6 non responsive forms
19
Q

Classical Homocystinuria

  • cause
  • mode of inheritance
A

CBS deficiency (Cystathionine B- Synthase)

-all of these are Auto recessive!

20
Q

Homocystinuria tx

A
  1. Pyridoxine (B6) if pt has responsive form
  2. Restrict dietary protein
  3. Methionine free food Supplement
  4. Oral Betaine
21
Q

When should valproate therapy be avoided?

A

If pt has elevated ammonia levels

22
Q

Most common urea cycle disorder

  • x linked
  • characteristic presentation
A

OTC (ornithine transcarbamylase) deficiency

PLasma aa:

  • Low citrulline
  • eleveated glutamine >1200

Urine acids
- elevated orotic acid

23
Q

Ammonia scavenging medications

A
  1. sodium phenylacetate

2. sodium benzoate