Inborn Errors of Metabolism Flashcards
What did Garrod propose
Garrod proposed that: Alkaptonuria Cystinuria Albinism Pentosuria Congenital (present at birth) Inborn (transmitted through the gametes) Had the discontinuous distribution of a Mendelian trait
Alkaptonuria - define
Black ochrontic pigmentation of cartilage & collagenous tissue
Alkaptonuria - characteristics
Autosmal recessive Urine turns black on standing (and alkalinisation) Arthritis Homogentisic acid oxidase deficiency
Cystinuria - define
Defective transport of cystine and dibasic aa’s through epithelial cells of renal tubule and intestinal tract
Cystinuria - cause
Mutations of SLC3A1 aa transporter gene (Chr 2p) & SLC7A9 (Chr 19)
AR
What 4 things did Beadle and Tatum propose
All biochemical processes in all organisms are under genetic control
These biochemical processes are resolvable into a series of stepwise reactions
Each biochemical reaction is under the ultimate control of a different single gene
Mutation of a single gene results in an alteration in the ability of the cell to carry out a single primary chemical reaction
Inborn errors of metabolism are caused by
Inborn errors of metabolism are caused by mutations in genes which then produce abnormal proteins whose functional activities are altered
Mechanisms of inheritance - list 5
Autosomal recessive Autosomal dominant X-linked Codominant Mitochondrial
Autosomal recessive - describe action, effect and examples
Both parents carry a mutation affecting the same gene
1 in 4 risk each pregnancy
Consanguinity increases risk of autosomal recessive conditions
Examples: Cystic fibrosis, sickle cell disease
Autosomal dominant - in IEMs and examples
Rare in IEMs
Examples: Huntingdon disease, Marfan’s, Familial hypercholesterolaemia
Describe passing of recessive X linked conditions - explain
Recessive X linked conditions passed through the maternal line
condition appears in males
condition carried in females, but not usually expressed. Female carriers may manifest condition –Lyonisation (random inactivation of one of the X chromosomes)
Describe passing of dominant X linked conditions - explain
Dominant X-linked conditions passed on from either affected parent
Affected father will only pass the condition to his daughters
Affected mother can pass the condition to sons and daughters
X-linked dominant: examples
X-linked dominant: Fragile X, Ornithine carbamoyl transferase deficiency
X-linked recessive: examples
X-linked recessive: Haemophilia A, Duchenne muscular dystrophy, Fabry’s disease
Codominant - describe w/examples
Codominant
two different versions (alleles) of a gene are expressed, and each version makes a slightly different protein. Both alleles influence the genetic trait or determine the characteristics of the genetic condition.
Example: ABO Blood group, α1AT
