Metabolic insight from genetic diseases Flashcards
(48 cards)
in newborn screening what are the inherited metabolic diseases that babies are tested for
- Phenylketonuria (PKU)
- Medium-chain acyl-CoA dehydrogenase deficiency (MCADD)
- Maple syrup urine disease (MSUD)
- Isovaleric acidaemia (IVA)
- Glutaric aciduria type 1 (GA1)
- Homocystinuria (pyroxidine unresponsive) (HCU).
what are inherited metabolic diseases caused by (simply)
- they are caused by a gene defects, this results in changed activity of a specific protein
what an inherited metabolic diseases be caused by
- This can be due to reduced synthesis, incorrect transport or altered amino acid composition (changes 3d shape or active site).
- It can be secondary, defects in regeneration of cofactor.
- Sometimes this can lead to the production of a toxic metabolite.
what are metabolic inherited diseases classed by
- often classed by phenotype and not genotype
what is an example of a carbohydrate metabolism disease
example of a carbohydrate metabolism disease is glycogen storage disease.
what is an example of an amino acid metabolism disease
example of amino acid metabolism disease is phenyl-keto urea, maple syrup urine disease, glutaric acidaemia type 1.
what is an example of organic acid metabolism disease
example of organic acid metabolism disease is alkaptonuria.
what is an example of fatty acid metabolism
example of fatty acid metabolism (mitochondrial defects) is medium chain acyl CoA dehydrogenase deficiency
How do you detect an inherited metabolic disorder
neonatal screening is done e.g help prick to test for PKU or MCAD.
- plasma metabolite analysis looks for build-up of abnormal metabolism e.g via mass spectrometry.
- screening of family members looking for specific genotypes, heterozygotes can be detected during screening and given genetic counselling.
these symptoms would signal what metabolic disorder
- hypoglycaemia
- cataracts
- metabolic acidosis
- unusal urine odour
- neurological dysfunction
- HYPOGLYCAEMIA glycogen storage disease
- CATARACTS galactosemia
- METABOLIC ACIDOSIS organic acid defects (PDC deficiency).
- UNSUAL URINE ODOUR amino acid and organic acid defects.
- NEUROLOGICAL DYSFUNCTION urea cycle defects as ammonia builds up in the blood.
how many people does Von Gierkes disease happen in
occurs in 1 in 43000
what is von gierkes disease
- it is a deficiency of glucose-6-phosphatase which reverses glucokinase/hexokinase reaction in the liver.
- this deficiency prevents the liver making its glycogen stores accessible to the rest of the body.
- and glucose cannot be synthesised in the liver from glucogenic amino acids and lactate.
what are the symptoms of Von Gierke’s disease
-hypoglycaemia, lactic acidosis and an enlarged liver are common signs and symptoms.
what is the treatment of von Gierke’s disease
-providing slow release sugar from starch is a treatment.
what causes Her’s disease
- deficiency in liver phosphorylase
- this prevents the liver making its glycogen stores accessible to the rest of the body
what are symptoms of Her’s disease
-signs are hepatomegaly, hypoglycaemia and more lactate and lipids in blood
what are treatments of Her’s disease
-treatment is to provide regular starch
describe what causes McArdle’s disease
- autosomal recessive.
- unable to use muscle glycogen due to deficiency in muscle phosphorylase.
what are the symptoms of McArdle’s disease
- fast exercise results in rhabdomyolysis due to lack of energy, also raised blood creatine kinase and myoglobin (causes dark urine).
- 2nd burst in exercise.
How is McArdle’s diagnosed
-diagnosed with ischaemic forearm test (no lactate produced), biopsy and sequencing
how many people in Galactosameia type 1
-1 in 30-60000 births.
what causes Galactosaemia type 1
- deficiency in galactose-1-phosphate uridyl transferase.
- autosomal recessive disease where baby can’t use galactose portion of lactose.
- galactose and galactose-1-phophate accumulate in tissue and galatcose-1-phosphate in the blood.
What are the symptoms of galactosaemia type 1
hypoglycaemic, acidosis and will later develop cataracts and mental retardation
what is the treatments for galactosaemia type 1
treatment is via a galactose free diet, if untreated, patients will die.
