Inborn Errors Of Metabolism Flashcards
What are the Inborn Errors of Metabolism?
A group of rare genetic disorders that result from a block to an essential pathway in the metabolism
Name the 3 pathophysiological subgroups that we divide IEMs into
- Toxic accumulation
- Defects in energy production/ use due to deficiency of products
- Disorders of complex molecules involving organelles
What things can accumulate toxically in inborn errors of metabolism?
- Substrates
- Intermediates from alternative metabolic pathways
What can inborn errors of metabolism vary in?
Age of onset and clinical severity
What are the 4 disorders studied by Garrod?
- Alkaptonuria
- Cystinuria
- Albinism
- Pentosuria
What is Alkaptonuria?
- Urine turns black on standing (and alkalinisation)
- Black ochrontic pigmentation of cartilage and collagenous tissue
- Homogentisic acid oxidase deficiency
- Autosomal recessive disease
- Congenital
What did Archibold Garrod propose the disorders were?
- Congenital
- Inborn
- Followed mendels laws of inheritance
Define congenital
present at birth
Define inborn
Transmitted through gametes
Who came up with the one gene- one enzyme concept?
Beadle and tatum
What does the one gene-one enzyme concept mean?
Mutation of a single gene results in an alteration in the ability of the cell to carry out a single primary chemical reaction
What is an example of molecular disease concept?
Gene mutations produce an alteration in the primary structure of proteins by hamoglobin in sickle cell diesase
What are the four mechanisms of inheritance?
- Autosomal recessive
- Autosomal dominant
- X-linked
- Mitochondrial
Who transfers autosomal recessive inheritance?
Both parents carry a mutation affecting the same gene
What is the risk size in each autosomal recessive pregnancy?
1 in 4
What increases the risk of autosomal recessive conditions?
Cosanguinity
What are some examples of autosomal recessive diseases?
- PKu
- alkaptonuria
- McADD
Are autosomal dominant conditions rare or common in IEMs?
Rare
What are some examples of autosomal dominant diseases?
- Marfans
- acute intermittent porphyria
How are X-linked mutations passed down?
Maternal line
Where do X-linked diseases appear and where are they carried?
- Appear in men
- carried in women
What is lyonisation?
Random inactivation of one of the X chromosomes in women so X-linked conditions can manifest in female carriers
What are some examples of X-linked conditions?
- Fabrys disease
- ornithine carbamoyl transferase deficiency
What are mitochondrial diseases?
Mitochondrial diseases are chronic, genetic disorders that occur when mitochondria fail to produce enough energy for the body to function properly
Where are mitochondrial diseases inherited from?
Mother
Which gender do mitochondrial diseases affect?
Male and female offspring