ChemPath: Metabolic Screening and Disorders 1 Flashcards

1
Q

Which database keeps track of all inherited metabolic disorders?

A

OMIM

Online Mendelian Inhertiance in Man

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2
Q

What is the basic pathogenesis of inherited metabolic disorders?

A

Enzyme deficiency

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3
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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4
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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5
Q

What is phenylketonuria caused by?

A

Phenylalanine hydroxylase deficiency

  • This enzyme is responsible for converting phenylalanine to tyrosine
  • Deficiency results in an accumulation of phenylalanine which is toxic
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6
Q

Which metabolite would be detected in urine in PKU?

A

Phenylacetic acid

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7
Q

What is the main consequence of untreated PKU?

A

Progressive developmental delay and learning disability

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8
Q

How is PKU investigated?

A

Blood phenylalanine level (detected in Guthrie test)

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9
Q

Describe the treatment of PKU.

A
  • Diet low in phenylalanine and high in tyrosine
  • Regular monitoring of blood phenylalanine
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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? How is diagnosed?

A
  • Thyroid dysgenesis or agenesis
  • Diagnosis is based on high TSH
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12
Q

How is cystic fibrosis detected in the neonate (Guthrie test)?

A

High blood immune reactive trypsin (IRT)

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13
Q

Outline the pathophysiology of cystic fibrosis.

A
  • Defective CFTR function
  • Reduced chloride secretion in lumen by epithelial cell
  • Increased sodium reabsorption, which results in increased water reabsorption
  • Increased viscosity of secretions
  • Lumen blockage
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14
Q

Describe the pathophysiology of MCAD deficiency.

A

This is a fatty acid oxidation disorder

  • Without MCAD, patients will not produce acetyl-CoA from fatty acids, which is necessary in the TCA cycle to produce ketones
  • Patient is unable to utilise fat in carbohydrate deficient states (fasting, infection, exercise), resulting in severe hypoketotic hypoglycaemia
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15
Q

What is the screening test for MCAD deficiency?

A

Measuring C6-C10 acylcarnitines by tandem MS (part of Guthrie test)

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16
Q

Outline the treatment of MCAD deficiency.

A
  • Strict avoidance of fasting
  • Diet high in carbohydrate and low in fats
17
Q

What is homocystinuria caused by?

A

Failure of homocysteine metablism

Numerous enzymes deficiencies responsible
e.g. methionine synthase deficiency (converts homocysteine to methionine)

18
Q

What are the clinical features of homocystinuria?

A
  • Lens subluxation
  • Mental retardation
  • Thromboembolism