Who is at Risk? What causes Pyruvate Dehydrogenase Complex Deficiency?
Scientist believe that Pyruvate Dehydrogenase Complex Deficiency(PDCD) is hereditary; It is a metabolic disorder caused by mutation in the PDHA1 gene. The mutation is a type of X-linked recessive inheritance. Usually X-linked diseases occurs in males, however, PDCD affects a equal number of male and female. This is because males only have one X chromosome and will not form barr bodies in order to inactivate the mutated PDHA1 gene found on the X chromosome.
Why are females Affected although it is a X-linked disease?
Reason 1
Females have two X-chromosomes, therefore one of the X chromosome will from barr bodies in order to inactivate one of the X chromosome. This can occur randomly(X-inactivation) or not randomly(skewed X-inactivation). Unfortunately in PDCD, scientist found that skewed X-inactivation occurs, this means that the X chromosome containing the normal PDHA1 gene is inactivated instead through the formation of barr bodies. This skewed X-inactivation results in the expression of mutated PDHA1 gene resulting in PDCD. However it is possible for skewed X-chromsome to inactivate mutated PHDA1 gene instead resulting in the female just becoming a carrier of the mutated PHDA1 gene that she can pass on to her offspring.
Reason 2
The father and mother of the child passes on both X-Chromsome containing mutated PDHA1 gene resulting in homozygous expression. However, the most common cause of PDCD in females is due to skewed X-inactivation because many of those born with PDCD do not usually survive past childhood in order to reproduce. There is currently no cure for PDCD, however, there is treatment in the form of a Ketogenic diet.
Metabolic disorder: A inherited genetic disease that causes a defect in a single gene that codes for a single enzyme that converts substrate (e.g glucose) thus the substrate cannot be broken down.
PDHA1: Pyruvate dehydrogenase (lipoamide) alpha 1
X-linked recessive inheritance: a mutation in the gene of the X chromosome which results in the expression of the mutated phenotype
Ketogenic diet: Is a diet rich in fat but low in carbohydrates (more on the Ketogenic diet will be found in a later post)
Hello! :) What are barr bodies? Do they have any function?
ReplyDeleteBarr bodies are basically inactivated X chromosomes in female somatic cells. Males have XY chromosomes and females have XX chromosomes. Different informations are stored in the X and Y chromosomes. Since there are 2 X chromosomes in female somatic cells, the expression of the information will be doubled. To prevent this, one of the X chromosomes is being inactivated and condensed so to prevent the double expression. Thanks for the question!
DeleteSo can people get this genes from a non-hereditarily
ReplyDeleteHi Malcolm, pyruvate dehydrogenase complex is a genetic x-linked genetic disease which means those with pyruvate dehydrogenase complex deficiency are born with this deficiency. It is not possible for a person born without pyruvate dehydrogenase complex deficiency to develop it later in life.
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