Lecture 11: Inherited Metabolic Diseases

Question 1

When do inherited metabolic diseases present in life?

Answer 1

Early in childhood but can present more widely

Question 2

What causes the IMD to present? (2)

Answer 2

Build up of precursor/intermediary metabolite
Product deficiency

Question 3

What factors are used to classify IDM?

Answer 3

Disorders that give rise to intoxication
Disorders involving energy metabolism
Disorders involving complex molecules

Question 4

What does intoxication mean in the context of IMD?

Answer 4

Too toxic of an environment for cells to survive.

Question 5

PKU, Porphyria, Organic acidurias (MMA), urea cycle defects, Wilson disease, are examples of what type of IDM?

Answer 5

Disorders that give rise to intoxication

Question 6

Mitochondrial defects, fatty acid oxidation defects (MCADD), Respiratory chain defects, are examples of what type of IDM?

Answer 6

Disorders involving energy metabolism

Question 7

Lysosomal storage disorders, Gaucher disease, are examples of what type of IDM?

Answer 7

Disorders involving complex molecules

Question 8

What can help diagnose IMD in symptomatic patients?

Answer 8

Clinical history
Genetic testing
Histology
Blood/urine test

Question 9

What can help diagnose IMD in a whole population?

Answer 9

Screening programmes/Targeted screening

Question 10

Why are urine tests helpful for blood disorders?

Answer 10

You can see crystals of the affected amino acid within the urine

Question 11

ToD: All inherited disorders are life threatening

Answer 11

False
They can affect quality of life OR be life threatening

Question 12

What is the name of the post-natal screening process?

Answer 12

Newborn blood spot (heel prick) test

Question 13

What can the heel prick test test for? (8)

Answer 13

Phenylketonuria
Hypothyroidism
Cystic fibrosis
Sickle cell disease
MCADD
Galactosaemia
CAH
Duchenne muscular dystrophy

Question 14

What can be seen in infants if they have a low level of phenylalanine?

Answer 14

Poor weight gain

Question 15

Where can phenylalanine be found in foods?

Answer 15

High protein foods
Ingredient to Aspartame (artificial sweetener)

Question 16

What does phenylalanine do in the body?

Answer 16

Helps the body use enzymes and amino acids in the body.
Can be converted into norephinephrine and epinephrine

Question 17

Another name for Hypotonia

Answer 17

Floppy baby

Question 18

Describe what you should see in a baby with Hypotonia (floppy baby)

Answer 18

Baby hangs there when held up. Completely limp inside of squirming and moving its legs.
Baby legs should tense and should bend like a v shape.

Question 19

What does FISH stand for?

Answer 19

Fluorescence in situ hybridisation.

Question 20

What is FISH used for?

Answer 20

Can be used to run tests on a single cell to scan for multiple abnormalities
Couples with a history of birthing children with genetic diseases can have embryos screened to check for MD.
IVF is used to implant the embryo without a genetic disease

Question 21

Which chromosomes are checked during FISH? (9)

Answer 21

X
Y
13
14
15
16
18
21
22

Question 22

What can a disorder with the 9 chromosomes result in for the mother?

Answer 22

Spontaneous abortion

Question 23

What are some concerns with Pre-Natal Genetic Scanning?

Answer 23

Designer babies
Sex-selection

Question 24

What are some positives for Pre-Natal Genetic Scanning?

Answer 24

Reproductive beneficence

Question 25

If IMD is suspected, what are some first line tests? (8)

Answer 25

Glucose (low/hypoglycaemia) Ammonia (raised/hyperammonaemia) LFTs (raised/liver enzymes or hyperbilirubinaemia) Lactate (raised/lactic acidosis) CK FBC Blood gases Urine ketones

Question 26

How many known lysosomal disorders are there?

Answer 26

40

Question 27

How is each lysosomal disorder differentiated between each other?

Answer 27

Transporters Activators Enzymes

Question 28

What can happen due to having a lysosomal disorder?

Answer 28

Toxic build up of partially denatured substrates

Question 29

ToD: Most lysosomal disorders are autosomal recessive conditions?

Answer 29

True

Question 30

How long does it take to present with symptoms of a lysosomal disorder?

Answer 30

3-6 months of life

Question 31

Why is it important to keep track of a baby's status/stats e.g weight?

Answer 31

Easier to identify lysosomal disorders

Question 32

What are the names of the different lysosomal storage disorders that can occur? (4)

Answer 32

Lipid/sphingolipidoses Glycoproteinoses/mucolipidoses Mucopolysaccharidoses Others

Question 33

Name some examples of Sphingolipidoses (2)

Answer 33

Gaucher Tay-Sachs

Question 34

Name some examples of Glycoproteinoses/mucolipidoses (2)

Answer 34

Mannosidosis I-cell disease

Question 35

Name some examples of Mucopolysaccharidoses (3)

Answer 35

MPS disorders Hurler Hunter

Question 36

Name some examples of Other lysosomal storage disorders (3)

Answer 36

Pompe Cystinosis Battens

Question 37

Which is the most common disease amongst all the ones mentioned?

Answer 37

Gaucher

Question 38

Name the neurological symptoms that can appear in lysosomal storage diseases (5)

Answer 38

Developmental delay/regression Behavioural disturbance Intellectual disability Hypotonia, developing spasticity Seizures

Question 39

Name the ophthalmological symptoms that can appear in lysosomal storage diseases (3)

Answer 39

Macular cherry-red spots Optic atrophy Corneal clouding

Question 40

Name the Craniofacial symptoms that can appear in lysosomal storage diseases (3)

Answer 40

Coarse features Macroglossia Large, low-set ears

Question 41

Name the Skeletal symptoms that can appear in LSD (3)

Answer 41

Spinal abnormalities Broad hands and feet Brachydactyly

Question 42

Name the Abdominal that can appear in LSD (3)

Answer 42

Hepatosplenomegaly Inguinal hernia

Question 43

Name the Haematological that can appear in LSD (4)

Answer 43

Vacuolated or granulated lymphocytes Foam cells Bone marrow abnormalities Cytopenias

Question 44

How is LSD managed?

Answer 44

Bone Marrow transplant (HSCT) Enzyme replacement Substrate reduction Gene therapy

Question 45

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