gentic disorders 2 Flashcards
When there are food/molecule outside of the cell
heterophagy
Dead organelle inside the organ has to be removed by_______
autophagy
catabolism of the substrate of the missing enzyme remains incomplete, leading to the accumulation of the partially degraded insoluble metabolite within the lysosomes.
Primary accumulation
Impaired autophagy gives rise to ________
secondary accumulation
-generation of free radicals and apoptosis
Type 2- pompe disease
Glycogenesis
-glycogen
GM1 ganglioside betagalactosidase
Sphingolipidoses
-GM1
Sphingomyelinase
Sulfate doses ex/ niemann pick disease
Alpha-liduronidase
Mucopolysacharidoses
-dermatan sulfate, heparin sulfate
Enzymes needed for the formation of mannose-6-phosphate recognition marker
Mucopolidoses
-mucopolysaccharides
Alpha fucosidase
Fucosidosis
is based on the premise that if the substrate to be degraded by the lysosomal enzymes can be reduced, the residual enzyme activity may be sufficient to catabolize it and prevent accumulation
subtrate reduction therapy
competitive inhibitor of the enzyme can bind to the mutant enzyme and act as the folding template that assists proper folding of the enzyme and thus prevents its degradation
molecular chaperone therapy
Results from mutations in the α-subunit locus on
chromosome 15 that cause a severe deficiency of
Hexosaminidase A
Tay-sachs disease
molecule composed of glycosphingolipid with one or more sialic acids linked on the sugar chain
gangliosides
involved in cell-cell recognition and adhesion and signal transduction
gangliosides
gangliosides are degraded to _________, catalyzed by a set of highly specific lysosomal enzyme (hexoseaminidase A)
ceramides
lysosomal accumulation of sphingomyelin due to inherited deficiency of sphingomyelinase
Niemann-pick disease types A and B
- severe infantile form with extensive neurologic involvement, marked visceral accumulations of sphingomyelin, and progressive wasting and early death within the first 3 years of life.
Type A
organomegaly but no CNS involvement. Patients usually survive into
adulthood.
Type B
Symptoms: o Enlarged liver and spleen, swelling in abdomen by around 3 months, which may progress with age o Feeding issues, failure to thrive o Frequent respiratory functions o Red spot in the eye o Irritability
Niemann-pick disease types A and B
NPC 1
membrane bound
NPC2
Soluble
mutations in gene encoding glucocerebrosidase (accumulates primarily in phagocytes)
Gaucher disease
-activation of macrophages
o Most common, accounting for 99% of cases
o Does not involve the brain
o Splenic and skeletal involvements dominate
o It is principally found in Jews of European
stock
type 1 or chronic non-neuropathic form
o No predilection for Jews
o Progressive CNS involvement leading to
death at an early age.
Type 2 or Acute Neuronopathic Gaucher
disease
o Systemic involvement of Type I but have
progressive CNS disease that usually begins
in adolescence or early adulthood
o Gaucher cells – distended phagocytic cells.
o Found in spleen, liver, bone marrow, lymph,
nodes, tonsils, thymus, and Peyer’s patches
(tissues with macrophages)
o With fibrillary type of cytoplasm (like crumpled
tissue paper)
Type 3 or Chronic Neuronopathic Form
The glycosaminoglycans that accumulate in MPSs
are
o Dermatan sulphate
o Heparan sulphate
o Keratan sulphate
o Chondroitin sulphate
hunter syndrome
x-linked
▪ Deficiency of α-I-iduronidase
▪ Life expectancy of children with MPS I-H is 6-10
years, and death is often a result of cardiac
complications
Mucopolysaccaridoses (MPS I-H) Hurler Syndrome
-Accumulation of dermatan and heparan sulphate is
seen in mononuclear phagocytes, fibroblasts and
within endothelium and smooth muscle cells of the
vascular wall.
Glucose-6-phosphatase
deficiency
Glycogenosis Type I
- Acid maltase deficiency
(AMD); Pompe disease
Glycogenosis Type II
Liver phosphorylase
deficiency
Glycogenosis Type VI
Brancher enzyme
deficiency; Andersen disease
Glycogenosis Type IV
Muscle phosphorylase
deficiency; McArdle disease
Glycogenosis Type V
- Debrancher enzyme
deficiency; Cori – Forbes disease
Glycogenosis Type III
Most familial cancers are inherited as _________
autosomal
dominant
Alternating pattern of
light and dark bands
Giemsa Stain
Any exact multiple of the haploid number (23)
Euploid
one homologous chromosome in meiosis
or one chromatid in mitosis lags behind and is left out of
the cell nucleus. The result is one normal cell and one cell
with monosomy.
Anaphase lag -
Non-Homologous Chromosomes (n)
HAPLOID
Pairs of Homologous Chromosomes (2n)
DIPLOID
When a normal egg combines with an aneuploid sperm it
will form 2n+1 (an extra chromosome). If the extra
chromosome happens in Chromosome 21 then it will be
________
Downs Syndrome.
special form of deletion.
Produced when the break occurs at both ends of a
chromosome ends
Ring chromosome
involves two breaks within a single
chromosome with reincorporation of the inverted,
intervening segment (not much problematic because
there is no genetic loss) The genes here will still be
present, therefore there is not much of a phenotypic
effect.
Inversion
when one arm of a chromosome
is lost and the remaining arm is duplicated, resulting
in a chromosome consisting of two short arms only or
of two long arms.
Isochromosome
the small
chromosome is unfortunately lost. One of the
causes of down syndrome- which is not in excess
of chromosome but an excess of chromosomal
material.
Robertsonian translocation
disorders – DiGeorge syndrome and velocardiofacial
syndrome.
CHROMOSOME 22q11.2 DELETION SYNDROME
Trisomy 18
(Edwards syndrome)
Trisomy 13
Patau syndrome
Clinical features can be attributed to (1) aneuploidy
and the impact of increased gene dosage by the
supernumerary X and (2) presence of hypogonadism
KLINEFELTER SYNDROME (47, XXY)
Eunuchoid body habitus with abnormally long legs,
small atrophic testes often associated with a small
penis, lack od such secondary male characteristics as
deep voice, beard, and male distribution of pubic hair.
Gynecomastia may be present.
KLINEFELTER SYNDROME (47, XXY)
▪ Results from complete or partial monosomy of the X
chromosome
▪ Characterized primarily by hypogonadism in
phenotypic females
▪ Most common sex chromosome abnormality in
females
TURNER SYNDROME (47,X)
hermaphrodism and pseudo-hermaphrodism.
implies the presence of both
ovarian and testicular tissues. – It means to say that
they have an ovarian tissue that secretes estrogen
and a testicular tissue which secrets testosterone.
True hermaphrodite
represents a disagreement
between the phenotypic (what is being seen) and
gonadal sex (genotype) (i.e., a female pseudohermaphrodite has ovaries but externally male
genitalia
Pseudo-hermaphrodite
▪ The prototype of diseases in which the mutation is
characterized by a long repeating sequence of three
nucleotides.
▪ Second most common genetic cause of mental
retardation after Down syndrome.
▪ It is caused by a trinucleotide mutation in the familial
mental retardation-1 (FMR1) gene
FRAGILE X SUNDROME
o Expansions affecting Noncoding regions:
- Fragile X syndrome
- Friedrich ataxia
- Myotonic dystrophy
Expansions affecting Coding regions:
- Spino-bulbar muscular atrophy
- Huntington disease
- Haw River syndrome
- Spino-cerebellar ataxia
all cases the deletion
affects the paternally derived chromosome 15.
Characterized by mental retardation, short stature,
hypotonia, profound hyperphagia, obesity, small
hands and feet, and hypogonadism.
Prader-Willi syndrome
deletion of the same
chromosomal region derived from their mothers:
characterized by mentally retarded, but in addition
they present with ataxic gait, seizures, and
inappropriate laughter. Because of their laughter
and ataxia, they have been referred to as “happy
puppets.”
Angelman syndrome
