GENETIC METABOLIC SYNDROMES Flashcards
what will be seen in a CF newborn ubale to pass stool
meconium ileus
blockage by ‘thick sticky’ first stool
what will be seen in a down syndrome patient unable to pass stool
Hurschprung’s disease
failure of migration of Auerbach myenteric plexus
in muscularis plexus between circular and longitudinal muscles
patient with Down syndrome is presenting what what conditon?
Why does it occur?
Is there bilious or non-bilious emesis?
duodenal atresia
failure of recanalisation of endodermal gut tube
bilious emesis
cri-du-chart results from ? of chromosome ?.
deletion
short arm chromsome 5
failure to thrive
dysmorhpic facial features
congenital heart defect (VSD)
high pitched cry
cri-du-chat
deletion short arm chromosome 5 - sporadic (not inherited)
microgenia
wide spaced eyes
flattened nasla bridge
slanting palpibral fissures
scoliosis, narrow iliac crests
transverse palmer crease
shortened metacarpals/tarsals
VSD
squeaky door cry
difficulty feeding
what heart defect is seen in Williams syndrome
supravalvular aortic stenosis
**chromosome 7 - long arm deletion
affects elastin gene
‘elfin’ like
pulmonary srtery stenosis
renal artery stenosis
(also seen)
wht effect do you see with calcium in Williams syndrome
hypercalcaemia
increased vitamin D sensitivity
Elongated facial features
large ears, head circumference
Intellectual delay, autistic behavior
macroorchidism
hypermobility
pes planus
mitral valuve prolapse
self mutilation
what is the condition & gene & genetic cause
Fragile X syndrome
FMR1 gene mutation
CGG trinucleotide repeat expansion
X linked inheritence
don’t confuse with Lesch-Nyhan (self mutilation)
what heart defect is seen in fragile X syndrome
mitral valve prolapse
inheritence of fragile X
AD
trinucleotide repeats in FMR1 gene causes what
hypermethylation of cytosine residues
**decreased expression **FMR1 gene ‘gene silencing’
Zellweger syndrome presents with elevated serum levels of
VLCFA
defect in peroxisome formation, which prevents catabolism of VLCFA
death 1yr
angelman syndrome results in uniparental disomy - inheriting both copies of -? chromosome -?
paternal
15
(mutation of maternal chromsome copies)
no copies of maternal chromosome 15
only ‘man’ shows up
imprinting - methylation (silencing)
prader-willi syndrome results in uniparental disomy - inheriting both copies of -? chromosome -?
maternal
15
(mutation of paternal chromsome copies)
no copies of paternal chromosome 15
imprinting - methylation (silencing)
girl
milestone regression
growth failure
wringing/rubbing hands
vocal grunting
ataxia
Rett syndrome
develop normally until 6-18mo
what gene is affected in Rett syndrome
MECP2 gene mutation
*(methyl-CpG binding protein 2)
on X chromosome
sporadic - de novo
behavioral problems
short stature
hyperphagia
facial dysmorphism
cryptorchidism
almond shaped eyes
thin upper lip
obesity
Prader-Willi syndrome
deletion of three base pairs in CTFR gene code for amino acid ?
phenylalanine
deltaF508
how does CTFR gene defect occur
chromosome 7
retention of mis-folded protein in RER
protein unable to reach surface
decreased Cl-, H2O secretion
what can be a later development in CF
exocrine pancreatic insufficiency
malabsorption
what proenzyme accumulates in the blood of newborns with CF
trypsinogen
proenzyme of trypsin
CTFR gene mutaiton -> chloride not properly reabsorbed –> remains in the lumen of apocrine sweat gland.
Positively charged sodium ions are also pathologically trapped in sweat by negatively charged chloride ions (balance net electric charge) –> resulting in
hypertonic sweat
increased sodium concentration in sweat
result of impaired Cl- ion transport
failure of ATP-gated Cl- channel leads to decreased Cl- in lung secretions. This in turn increases what
activity of **Na+ **channels
reabsorb Na+ ions into cells
(positive gradient is created)
stimulate passive **H2O reabsorption **from bronchial mucous into cells/interstitium
= thick bronchial secretions
seminal fluid no sperm
respiratory infections
clubbing
hepatomegaly, increased AST, ALT
binding of what to the channel protein is impaired
cystic fibrosis
ATP binding (ATP gated Cl- channels)
upper respiratory infections
nasal polyposis
pancreatic insufficiency
steatorrhea and malabsorption
failure to thrive,
should raise suspicion for …
cystic fibrosis
in Down syndrome quad screening what two levels are increased
inhibin A
HcG
‘HI’
cataracts
gonodal atrophy
early balding
**myotonic dystrophy **(GTG trinucleotide repeat)
female - reduced fertility
encephalopathy
lactic acidosis
stroke
childhood
MELAS
mitochondrial encephalopathy with lactic acidosis and stroke like episodes
mithcondrial mutations encoding MITO tRNA
lactic acidosis from impaired ox phos
myoclonic epilepsy
red ragged fibres
mitochondrial crystaline inclusions
MERRF
myclonic epilepsy with red ragged fibres
MK-TK gene - tRNA
gomori trichrome stain
leber hereditary optic neuropathy results from
mutations complex 1 of ETC
RETINA, OPTIC NERVE
SUBACUTE VISION LOSS
M>F
YOUTH
NEURO DYSF - TREMOR, MS
becker muscle dystrophy genetic defect
non-frameshift deletion in dystrophin
less severe, onset later than duchennes
onset teens/early adulthood
duchenne muscular dystrophy gene defect
frameshift deletion
or
non-sense mutation
can also result from splicing errors
‘deleted dystrophin’
onset infancy/early childhood
Degeneration of muscle fibers with fibrofatty replacement
duchenne muscular dystrophy
difficulty releasing hand grip
gene defect DMPK
myotonic dystrophy
trinucleotide repeat (GTG)
abnormal myotonin protein kinase
progressive dyspnea
holosystolic murmur
displaced point of maximal impulse
pitting edema
elevated brain natriuretic peptide (BNP)
associated with what muscular condition
dilated cardiomyopathy
assoc. with
duchenne / becker
dystrophin ‘anchoring’ filament in skeletal and cardiac muscle
raised CK
raised aldolase
deleted dystrophin
duchenne musclar dystrophy
becker and duchenne inheritence
X linked recessive
myotonic dystophy - AD
AR
secondary arthritis 2nd 3rd MCP
chondrocalcinosis
liver disease
skin hyperpigmentation
DM
central hypogonadism
cardiomyopathy
hereditary haemochromatosis
excessive GIT iron absorption
