ChemPath: Metabolic Screening and Disorders 1 Flashcards

1
Q

Which database keeps track of all inherited metabolic disorders?

A

OMIM

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2
Q

What are the main consequences of deficient enzyme activity in the context of inherited metabolic disorders?

A

Lack of end-product

Build-up of precursors

Abnormal or toxic metabolites

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3
Q

What are the criteria for inherited metabolic disorder screening (Wilson and Junger)?

A
  • It has to be an important health problem
  • Must be accepted treatment
  • Facilities for diagnosis and treatment
  • Latent or early symptomatic stage
  • Suitable test or examination
  • Test should be acceptable to the population
  • Natural history is understood
  • Agreed policy on whom to treat as patients
  • Economically balanced
  • Continuing process (keep updating what is screened for)
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4
Q

What is phenylketonuria caused by?

A
  • Phenylalanine hydroxylase deficiency
  • This enzyme is responsible for conerting phenylalanine to tyrosine
  • Deficiency results in an accumulation of phenylalanine which is toxic
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5
Q

Which abnormal metabolites are produced in PKU?

A

Phenylpyruvate

Phenylacetic acid (detected in the urine)

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6
Q

What is the main consequence of untreated PKU?

A

Low IQ<50

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7
Q

How is PKU investigated?

A

Blood phenylalanine level

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8
Q

Describe the treatment of PKU.

A
  • Monitor the diet and ensure that the patient is having enough phenylalanine (but not too much)
  • This must be started within the first 6 weeks of life
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9
Q

What does positive predictive value depend on?

A

disease prevalence: true positive/ total positive

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10
Q

When is the Guthrie test performed in the UK?

A

5-8 days after birth

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11
Q

What is congenital hypothyroidism usually caused by?

A
  • Thyroid dysgenesis or agenesis

NOTE: diagnosis is based on high TSH

done via guthrie screening

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12
Q

Describe the pathophysiology of MCAD deficiency.

A
  • This is a fatty acid oxidation disorder
  • The carnitine shuttle transports fats into the mitochondria where it will be broken down into smaller and smaller chains by the process of fatty acid oxidation
  • Without MCAD, you will not produce acetyl-CoA from fatty acids, which is necessary in the TCA cycle to produce ketones (which spares glucose)
  • Fat is used when fasting in between meals in order to spare your glucose stores
  • In MCAD deficiency, the patient is unable to break down fats so they become very hypoglycaemic in between meals and this can kill
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13
Q

What is the screening test for MCAD deficiency?

A

Measuring C6-C10 acylcarnitines by tandem MS

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14
Q

Outline the treatment of MCAD deficiency.

A

Make sure the child never becomes hypoglycaemic, and hence reliant on fats as a source of energy.

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15
Q

What is homocystinuria caused by?

A

Failure of remethylation of homocysteine

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16
Q

What are the clinical features of homocystinuria?

A
  • Lens dislocation
  • Mental retardation
  • Thromboembolism
17
Q

Which conditions are currently being trialled for inclusion in the newborn screening programme?

A
  • Homocystiinuria
  • Isovaleric acidaemia
  • Glutaric aciduria type I
  • Maple syrup urine disease
  • Long-chain acyl-CoA dehydrogenase deficiency
18
Q

How many classes of cystic fibrosis are there?

A

6

19
Q

Outline the pathophysiology of cystic fibrosis.

A
  • Failure of the cystic fibrosis transmembrane conductance regulator means that chloride ions cannot move into the lumen from the cells, resulting in increased water absorption and very thick secretions
20
Q

What is the screening test for cystic fibrosis?

A

High serum immune reactive trypsinogen

21
Q

Describe the process of screening and diagnosis of cystic fibrosis.

A
  • If IRT > 99.5th centile in 3 bloodspots, move on to mutation detection
  • There are >500 mutations that can cause cystic fibrosis, but FOUR are very common
  • If you detect 2/4 mutations, diagnose CF
  • If you detect 1/4 mutations, extend test to panel of 28 mutations
  • If you detect 0/4 mutations, repeat IRT at day 21-28