Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

302 SBM: Metabolic & Renal > Inherited metabolic disorders > Flashcards

Inherited metabolic disorders Flashcards

1
Q

What are the common characteristics of an inheritd metabolic disorder?

A
  • under-diagnosed
  • most autosomal recessive
  • normal at birth, become symptomatic later (exacerbated by diet or illness)
  • mimics sepsis but without known risk factors
  • can lead a normal life if managed early before irreversible organ damage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How might a patient with an inherited metabolic disorder appear?

A
  • non specific symptoms mimicking sepsis
  • poor feeding, vomiting, lethargy, seizures, coma
  • not responsive to glucose or calcium
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How are patients investigated?

A

There are a few screening tests available
e.g. plasma ammonia, blood gas (acidosis), urine for metabolites

Specific tests

  • blood tests
  • tissue samples
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How can amino acid disorders be subdivided?

A

TRANSPORT DISORDERS

  • dibasic amino acids (cystinuria)
  • neutral amino acids (Hartnup disease)

METABOLIC DISORDERS

  • phenylalanine/tyrosine
  • urea cycle defects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is cystinuria?

A

Autosomal recessive inherited metabolic disorder

Disorder: defective cystine transporter which causes high levels of cystine in urine which crystallises to form stones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How do you manage cystinuria?

A
  • In the symptomatic patient
  • prevent stone formation: increased water intake, alkalisation
  • lithotripsy (shock waves to break up stones), chelation (to sweep up excess cysteine)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How does phenylketonuria present?

A

Normal at birth

Gradually develop neurophysiological problems: microcephaly, low IQ, sezuires, tremors, impaired myelination

Blonde hair

Musty odour

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe the MOA of phenyloketonuria

A

PKU

  • Phenylalanine hydroxylase is deficient in PKU
  • so phenylalanine builds up as its conversion to tyrosine is inhibited
  • Tyrosine is needed to make melanins, fumarate and acetoacetate

Instead, phenylalanine is shunted into another pathway where it is converted to phenylpyruvate (toxic) by transaminase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How is phenylketonuria managed?

A
  • Diet
  • LDOPA ; Serotonin
    (think about MOA: tyrosine is needed to make dopamine and NA, and tryptase which is the precursor of serotonin)
  • Carefully manage mothers with PKU as foetus affected too. National screening of neonates available

Early treatment reduces neuro impairment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

This question is about urea cycle defects

What are the precursor molecules that are raised in urea cycle defects?

How do they present?

Hallmark on blood test?

A

Glutamine, glutamic acid, aspartic acid, glycine

Present soon after birth: lethargy, poor feeding, seizures, coma, death
If left untreated fatal

Hyperammonaemia, alkalosis, normal LFT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe the urea cycle

A

Protein catabolism produces amino acids glutamine, glutamic acid, aspartic acid and glycine. These form ammonia

Carmbamyl phosphate synthase converts this amonium to carbamyl phosphate which enters the urea cycle

Here it combines with omithin to form citrulline

Citrulline combines with aspartate to form argino-succinic acid (arginosuccinate synthase)

Argino-succinic acid is converted to argenine which is (a) converted to urea and excreted as urine (b) converted to omithine to replace it in step 2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How will a dysfunction in one of the enzymes in the urea cycle cause hyperammonaemia?

A

Will decrease urea production and reduce amount of omithin which together with carbamyl phosphate produce citrullline

If carbamyl phosphate is not being accepted into the urea cycle, conversion of ammonia to carbamyl phosphate will cease and ammonium will build up

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe the management of UCD

A
  • reduce dietary protein intake
  • remove the excess ammonia (Levulose)
  • remove the excess precursors: sodium benzoate will remove glycine and sodium phenylbutyrate will remove glutamate
  • replace intermediates not being synthesised due to enzyme deficiency: citrulline, arginine
  • liver transplant
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

This question is about glycogen storing disease 1 (GSD1)

What is the enzyme deficiency?

A

Glucose 6 phosphatase deficiency

- key enzyme in gluconeogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How does GSD1 present?

A
  • hypoglycaemia
  • lactic acidosis
  • lipidaemia
  • hepatomegaly
  • uricaemia
  • neutropenic
  • bruising
  • renal disease

(short stature, obesity, hypotonia)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the management of GSD1?

A
  • continuous feeds or corn starch
  • limit other sugars: fructose, galactose, sucrose, maltose
  • reduce uricaemia using Allopurinol
  • statins for lipid control
  • liver transplant
17
Q

What is the disorder caused by a GAL1PUT deficiency called?

How does it present?

How is it managed?

A

Galactosaemia
- Galactose-1-phosphate uridyl transferase deficiency

Poor weight gain, prolonged jaundice, cataracts, hepatomegaly

Galactose free diet (dairy milk), advise soy milk

18
Q

Give an example of an organic acid disorder?

A
  • Maple syrup urine disease

- MCAD deficiency

19
Q

What is MCAD deficiency?

A

Autosomal recessive organic acid disorder whereby there is a problem in fatty acid oxidation. Medium-chain Acetyl-CoA dehydrogenase is involved in mobilising fatty acids to produce energy

20
Q

Why do patients with MCAD become really unwell?

A

When these patients are normo-glycaemic they are well

When they are unwell or fasting they quickly become hypoglycaemic which can be dangerous

This is because they cannot break down fatty acids to produce energy

21
Q

How do MCAD deficiency patients present?

A
  • in childhood
  • hypoglycaemic, hypoketotic with liver function
  • infection with vomiting may precede such an episode
  • multiorgan failure, death

May have a history of vomiting and drowsiness (any signs of hypoglycaemia) which is relieved by sugary drinks

22
Q

Which investigation result will prompt you to consider a diagnosis of MCAD deficiency?

A

Elevation of medium-chain acylcarnitines

  • particularly C8 (largest spike)
  • and C6, C10

Reduction in total carnitine, free carnitine: acyl carnitine ratio

23
Q

How do you manage MCAD deficiency?

A
  • avoid fasting
  • consume slow release carbohydrates e.g. starch (to provide glucose overnight)
  • supplement Carnitine
  • Riboflavin: benefits some patients with electron transport chain deficiency
  • Medic-Alert Bracelet
24
Q

What are lysosomes?

A
  • spherical vesicles containing >50 hydrolytics enzymes
  • involved in phagocytosis, endocytosis and autophagy
  • the stomach of the cell contains suicide bags or sacs and recycling unit
25
Q

What are mucopolysaccharidoses?

State 3 diseases that fall under this category

How are they managed?

A

Inherited metabolic disorders caused by an absence or defect in enzymes needed to break down glycosaminoglycans

Hunters, Sanfilippo, Hurlers

Symptomatic treatment

26
Q

What are the features of a patient with mucopolysaccharidoses

A 
Gargoyle cells (fibroblast containing large deposits of mucopolysaccharide)
Coarse facies
Mental retardation
Short stature
Contractures
Dystostosis multplexa
27
Q

Give an example of a lipid storage disorder

A 
Gangliosidosis
Tay Sachs
Gaucher
Niemann Pick
Mucolipidoses
Lipofuscinosis

(These are lysosomal storage disorders)

28
Q

What are signs of lysosomal storage disorders

A

Neuroregression

  • seizures
  • hepatosplenomegaly
  • haematologic (anaemia)
  • skeletal signs (pathological fractures)
  • cherry red spot (in eye)
29
Q

What is the treatment for lysosomal storage disorders?

A
  • Enzyme replacement

- Liver transplant

30
Q

How are mitochondrial disorders inherited?

What are they?

How do they present?

A

Inherited by maternal mitochondrial DNA

Respiratory chain defects cause problems in energy production

Brain, eye, heart and muscle problems

31
Q

What is Leigh’s disease?

A

Subacute necrotising encephalomyelopathy

can cause loss of skills, epilepsy and problems with muscle function

32
Q

What is the treatment and prognosis for mitochondrial disorder?

A

Symptomatic treatment

Death in early life

33
Q

Describe the process of pronuclear transfer

A
  1. Egg with abnormal mitochondria fertilised by IVF
  2. Embryo with abnormal mitochondria is formed
  3. A donor egg with health mitochondria is used and the nuclear DNA from the abnormal cell is added to it
  4. This produces an embryo with healthy mitochondria with the nuclear DNA of its given mother
34
Q

Give an example of a peroxisomal disorder that leads to production and decomposition of peroxide

A
  • Zellwegers
  • Refsum
  • Adrenoleudystrophy
35
Q

How do peroxisomal disorders cause disease ?

How are they managed?

A

Accumulation of very low chain fatty acids (VLCFAs) in adrenal glands and peripheral nerves

Cause import/export defects

Diet
Bone marrow transplantation

302 SBM: Metabolic & Renal (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions