28 Genetic hormonal deficiencies Flashcards
what causes disease
can be caused by genetic and/or environmental factors
example of genetic factor that can cause disease
gene mutations, example of genetic disorder=colour blindness
how do gene mutations cause disease
genes are regions of DNA that encode for production of proteins
gene mutations cause disease by disrupting the function or expression of cellular proteins
what is DNA contained in
chromosomes
what do chromosomes contain
genes and non coding DNA
how many chromosomes does the haploid human genome have
23 –
22 autosomes and one seex chromosome (X or Y)
where are haploid copies of human genome found
in egg and sperm cells
what does the diploid human genome contain
46 chromosomes
where are diploid human genomes found
in somatic cells
how do cells have two copies of every gene
because they have two copies of each chromosome
(except X and Y in men)
does every cell have the same set of genes
yes but they’re switched on/off depending on the cell
different types of point mutations
- silent mutation
- nonsense
- missense (conservative nad non conservative)
what are silent mutations
the mutation occurs but has no effect
what are point mutations
changes a base to a stop codon
what is a conservative missense mutation
the substitution of similar but not identical amino acids
what is a non conservative missense mutation
occur when the new amino acid has different properties
where do mutations occur
within the coding sequence
how do mutations in non-coding DNA impact proteins
- may have no effect
- may affect protein expression
what is an autosomal dominant disease
when a mutation in one allele causes the disease
the diseased gene is dominant - even if they have a second copt they will still have disease
what percentage is there of passing an autosomal disease on to children
50%
what do autosomal recessive diseases require
both alleles to carry the mutation
what is the percentage of 2 parent carriers passing on an autosomal recessive mutation
25%
what is a congenital disorder
a disorder that’s present at birth
are genetic diseases always congenital
no eg huntington’s
is hypothyroidism present at birth
yes
what is hypothyroidism
low levels of thyroid hormones
symptoms of hypothyroidism in infants
- jaundice
- low body temp
- poor muscle tone
- excessive sleeping
what can hypothyroidism lead to if untreated
- reduced growth
- intellectual dysfunction
causes of congenital hypothyroidism
genetic defects in
- thyroglobulin gene (TG)
- sodium-iodide symporter genes
- TSH genes
- TSH receptor genes
what does TSH do
cause release of thyroid hormone
treatment of congenital hypothyroidism
oral thyroxine (T4) given daily
how are newborns tested
a heel prick procedure where blood is taken and measured for levels of T4 and TSH
what is allan-hernon-dudley syndrome
rare disorder caused by loss of function mutation in MCT8 genes (x-linked)
symptoms of allan-heron-dudley syndrome
- severe cognitive deficiency
- most affected males never walk
- most never speak
what does MCT8 do
move thyroid hormone into the target cells
how to treat Allan-hernon-dudley syndrome
diiodothyroproinoic acid (DITPA)
has same effect as thyroxine but is membrane permeable
what is isolated growth hormone deficiency
an autosomal recessive condition caused by a shortage or absence of growth hormone,, varies in severity
what causes isolated growth hormone deficiency
most congenital cases are idiopathic
but mutations have been identified in:
- GH1 gene encoding growth hormone
- GHRHR gene encoding growth hormone releasing hormone receptor
does GH deficiency have an effect on prenatal growth
not a major one
when is impaired length growth noted in isolated growth hormone deficiency
from a few months of age
can affected children ever reach normal height with isolated growth hormone deficiency
yes if its treated early
how to treat isolated growth hormone deficiency
with daily injections of GH
need to be injections as its a protein hormone
what type of hormones does the adrenal medulla secrete
amine hormones
(80% epinephrine, 20% norepinephrine)
what type of hormones does the adrenal cortex
steroid hormones
(aldosterone, cortisol, adrenal androgens)
when do adrenal androgens become detectible
from about 6 years old
what is DHEAS converted to and in where
in peripheral tissues
to more potent androgens, testosterone and dihydrotestosterone or to estradiol
in MALES is the conversion of adrenal androgens more or less than the synthesis of active androgens by testes
the peripheral conversion of adrenal androgens is much less
what % of active androgens does the adrenal gland contribute to in females
50% of the active androgens
what is congenital adrenal hyperplasia (CAH)
an autosomal recessive disorder caused by a deficiency in enzymes needed to make cortisol and aldosterone
what does congenital adrenal hyperplasia (CAH) cause
the body to produce more androgens which causes inappropriate or early development of male characteristics
what does no feedback inhibition by cortisol cause (CAH)
ACTH levels rise which leads to a build up of cortisol precursors and enhanced production of androgens
overstimulation leads to overgrowth of adrenal gland (hyperplasia)
what are most cases of CAH caused by
mutations in the 21-hydroxylase gene
what does mutation in 21-hydroxylase gene do
cause 21-hydroxylase deficiency which causes progesterone to be converted to 17-hydroxyprogesterone to adrenal androgens
instead of progesterone to aldosterone and 17-hydroxyprogesterone to cortisol
what deficiency do 90% of people with CAH have
21-hydroxylase deficiency
what deficiency do 8% of people with CAH have
11-B-hydroxylase deficiency
what can CAH cause (female genitalia)
- ambiguous genitalia
- virilised genitalia
treatments of CAH
- corticosteroids (eg oral hydrocortisone) to regulate blood glucose
- mineralocorticoids (eg oral fludrocortisone) to regulate salt conc in blood
- surgery to correct abnormal female genitalia (reduction clitoroplasty, construction of vaginal opening)
what deficiency do 8% of patients with CAH have
11-B-hydroxylase deficiency
CAH treatments
- corticosteroids, eg oral hydrocortisone (regulate blood glucose)
- mineralocorticoids, eg oral fludrocortisone (regulate salt conc in blood)
- surgery to correct abnormal female genitalia (reduction clitoroplasty, construction of vaginal opening)
what can CAH cause (female genitalia)
- ambiguous genitalia
- virilised genitalia
