Lecture 11: Inherited Metabolic Diseases Flashcards
When do inherited metabolic diseases present in life?
Early in childhood but can present more widely
What causes the IMD to present? (2)
Build up of precursor/intermediary metabolite
Product deficiency
What factors are used to classify IDM?
Disorders that give rise to intoxication
Disorders involving energy metabolism
Disorders involving complex molecules
What does intoxication mean in the context of IMD?
Too toxic of an environment for cells to survive.
PKU, Porphyria, Organic acidurias (MMA), urea cycle defects, Wilson disease, are examples of what type of IDM?
Disorders that give rise to intoxication
Mitochondrial defects, fatty acid oxidation defects (MCADD), Respiratory chain defects, are examples of what type of IDM?
Disorders involving energy metabolism
Lysosomal storage disorders, Gaucher disease, are examples of what type of IDM?
Disorders involving complex molecules
What can help diagnose IMD in symptomatic patients?
Clinical history
Genetic testing
Histology
Blood/urine test
What can help diagnose IMD in a whole population?
Screening programmes/Targeted screening
Why are urine tests helpful for blood disorders?
You can see crystals of the affected amino acid within the urine
ToD: All inherited disorders are life threatening
False
They can affect quality of life OR be life threatening
What is the name of the post-natal screening process?
Newborn blood spot (heel prick) test
What can the heel prick test test for? (8)
Phenylketonuria
Hypothyroidism
Cystic fibrosis
Sickle cell disease
MCADD
Galactosaemia
CAH
Duchenne muscular dystrophy
What can be seen in infants if they have a low level of phenylalanine?
Poor weight gain
Where can phenylalanine be found in foods?
High protein foods
Ingredient to Aspartame (artificial sweetener)
What does phenylalanine do in the body?
Helps the body use enzymes and amino acids in the body.
Can be converted into norephinephrine and epinephrine
Another name for Hypotonia
Floppy baby
Describe what you should see in a baby with Hypotonia (floppy baby)
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.
What does FISH stand for?
Fluorescence in situ hybridisation.
What is FISH used for?
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
Which chromosomes are checked during FISH? (9)
X
Y
13
14
15
16
18
21
22
What can a disorder with the 9 chromosomes result in for the mother?
Spontaneous abortion
What are some concerns with Pre-Natal Genetic Scanning?
Designer babies
Sex-selection
What are some positives for Pre-Natal Genetic Scanning?
Reproductive beneficence
If IMD is suspected, what are some first line tests? (8)
Glucose (low/hypoglycaemia)
Ammonia (raised/hyperammonaemia)
LFTs (raised/liver enzymes or hyperbilirubinaemia)
Lactate (raised/lactic acidosis)
CK
FBC
Blood gases
Urine ketones
How many known lysosomal disorders are there?
40
How is each lysosomal disorder differentiated between each other?
Transporters
Activators
Enzymes
What can happen due to having a lysosomal disorder?
Toxic build up of partially denatured substrates
ToD: Most lysosomal disorders are autosomal recessive conditions?
True
How long does it take to present with symptoms of a lysosomal disorder?
3-6 months of life
Why is it important to keep track of a baby’s status/stats e.g weight?
Easier to identify lysosomal disorders
What are the names of the different lysosomal storage disorders that can occur? (4)
Lipid/sphingolipidoses
Glycoproteinoses/mucolipidoses
Mucopolysaccharidoses
Others
Name some examples of Sphingolipidoses (2)
Gaucher
Tay-Sachs
Name some examples of Glycoproteinoses/mucolipidoses (2)
Mannosidosis
I-cell disease
Name some examples of Mucopolysaccharidoses (3)
MPS disorders
Hurler
Hunter
Name some examples of Other lysosomal storage disorders (3)
Pompe
Cystinosis
Battens
Which is the most common disease amongst all the ones mentioned?
Gaucher
Name the neurological symptoms that can appear in lysosomal storage diseases (5)
Developmental delay/regression
Behavioural disturbance
Intellectual disability
Hypotonia, developing spasticity
Seizures
Name the ophthalmological symptoms that can appear in lysosomal storage diseases (3)
Macular cherry-red spots
Optic atrophy
Corneal clouding
Name the Craniofacial symptoms that can appear in lysosomal storage diseases (3)
Coarse features
Macroglossia
Large, low-set ears
Name the Skeletal symptoms that can appear in LSD (3)
Spinal abnormalities
Broad hands and feet
Brachydactyly
Name the Abdominal that can appear in LSD (3)
Hepatosplenomegaly
Inguinal hernia
Name the Haematological that can appear in LSD (4)
Vacuolated or granulated lymphocytes
Foam cells
Bone marrow abnormalities
Cytopenias
How is LSD managed?
Bone Marrow transplant (HSCT)
Enzyme replacement
Substrate reduction
Gene therapy
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