GENETIC METABOLIC SYNDROMES

Question 1

what will be seen in a CF newborn ubale to pass stool

Answer 1

meconium ileus

blockage by ‘thick sticky’ first stool

Question 2

what will be seen in a down syndrome patient unable to pass stool

Answer 2

Hurschprung’s disease

failure of migration of Auerbach myenteric plexus

in muscularis plexus between circular and longitudinal muscles

Question 3

patient with Down syndrome is presenting what what conditon?
Why does it occur?
Is there bilious or non-bilious emesis?

Answer 3

duodenal atresia
failure of recanalisation of endodermal gut tube
bilious emesis

Question 4

cri-du-chart results from ? of chromosome ?.

Answer 4

deletion
short arm chromsome 5

Question 5

failure to thrive
dysmorhpic facial features
congenital heart defect (VSD)
high pitched cry

Answer 5

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

Question 6

what heart defect is seen in Williams syndrome

Answer 6

supravalvular aortic stenosis

**chromosome 7 - long arm deletion
affects elastin gene

‘elfin’ like

pulmonary srtery stenosis
renal artery stenosis
(also seen)

Question 7

wht effect do you see with calcium in Williams syndrome

Answer 7

hypercalcaemia

increased vitamin D sensitivity

Question 8

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

Answer 8

Fragile X syndrome

FMR1 gene mutation
CGG trinucleotide repeat expansion

X linked inheritence

don’t confuse with Lesch-Nyhan (self mutilation)

Question 9

what heart defect is seen in fragile X syndrome

Answer 9

mitral valve prolapse

Question 10

inheritence of fragile X

Answer 10

AD

Question 11

trinucleotide repeats in FMR1 gene causes what

Answer 11

hypermethylation of cytosine residues

**decreased expression **FMR1 gene ‘gene silencing’

Question 12

Zellweger syndrome presents with elevated serum levels of

Answer 12

VLCFA

defect in peroxisome formation, which prevents catabolism of VLCFA

death 1yr

Question 13

angelman syndrome results in uniparental disomy - inheriting both copies of -? chromosome -?

Answer 13

paternal
15

(mutation of maternal chromsome copies)

no copies of maternal chromosome 15
only ‘man’ shows up

imprinting - methylation (silencing)

Question 14

prader-willi syndrome results in uniparental disomy - inheriting both copies of -? chromosome -?

Answer 14

maternal
15

(mutation of paternal chromsome copies)

no copies of paternal chromosome 15

imprinting - methylation (silencing)

Question 15

girl
milestone regression
growth failure
wringing/rubbing hands
vocal grunting
ataxia

Answer 15

Rett syndrome

develop normally until 6-18mo

Question 16

what gene is affected in Rett syndrome

Answer 16

MECP2 gene mutation

*(methyl-CpG binding protein 2)

on X chromosome
sporadic - de novo

Question 17

behavioral problems
short stature
hyperphagia
facial dysmorphism
cryptorchidism
almond shaped eyes
thin upper lip
obesity

Answer 17

Prader-Willi syndrome

Question 18

deletion of three base pairs in CTFR gene code for amino acid ?

Answer 18

phenylalanine

deltaF508

Question 19

how does CTFR gene defect occur

chromosome 7

Answer 19

retention of mis-folded protein in RER

protein unable to reach surface
decreased Cl-, H2O secretion

Question 20

what can be a later development in CF

Answer 20

exocrine pancreatic insufficiency

malabsorption

Question 21

what proenzyme accumulates in the blood of newborns with CF

Answer 21

trypsinogen

proenzyme of trypsin

Question 22

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

Answer 22

hypertonic sweat
increased sodium concentration in sweat

result of impaired Cl- ion transport

Question 23

failure of ATP-gated Cl- channel leads to decreased Cl- in lung secretions. This in turn increases what

Answer 23

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

Question 24

seminal fluid no sperm
respiratory infections
clubbing
hepatomegaly, increased AST, ALT

binding of what to the channel protein is impaired

Answer 24

cystic fibrosis

ATP binding (ATP gated Cl- channels)

Question 25

upper respiratory infections nasal polyposis pancreatic insufficiency steatorrhea and malabsorption failure to thrive, *should raise suspicion for ...*

Answer 25

cystic fibrosis

Question 26

in Down syndrome quad screening what two levels are increased

Answer 26

inhibin A HcG | 'HI'

Question 27

cataracts gonodal atrophy early balding

Answer 27

**myotonic dystrophy **(GTG trinucleotide repeat) | female - reduced fertility

Question 28

encephalopathy lactic acidosis stroke childhood

Answer 28

**MELAS** mitochondrial encephalopathy with lactic acidosis and stroke like episodes | mithcondrial mutations encoding **MITO tRNA** ## Footnote lactic acidosis from impaired ox phos

Question 29

myoclonic epilepsy red ragged fibres mitochondrial crystaline inclusions

Answer 29

**MERRF** myclonic epilepsy with red ragged fibres | MK-TK gene - tRNA ## Footnote gomori trichrome stain

Question 29

leber hereditary optic neuropathy results from

Answer 29

mutations complex 1 of ETC ## Footnote RETINA, OPTIC NERVE SUBACUTE VISION LOSS M>F YOUTH NEURO DYSF - TREMOR, MS

Question 30

becker muscle dystrophy genetic defect

Answer 30

**non**-frameshift deletion in dystrophin | less severe, onset later than duchennes ## Footnote **onset teens/early adulthood**

Question 31

duchenne muscular dystrophy gene defect

Answer 31

frameshift deletion or non-sense mutation | can also result from splicing errors ## Footnote 'deleted dystrophin' **onset infancy/early childhood**

Question 32

Degeneration of muscle fibers with fibrofatty replacement

Answer 32

duchenne muscular dystrophy

Question 33

difficulty releasing hand grip gene defect DMPK

Answer 33

myotonic dystrophy trinucleotide repeat (GTG) | abnormal **myotonin protein kinase**

Question 34

progressive dyspnea holosystolic murmur displaced point of maximal impulse pitting edema elevated brain natriuretic peptide (BNP) | associated with what muscular condition

Answer 34

**dilated cardiomyopathy** assoc. with **duchenne / becker** | dystrophin 'anchoring' filament in skeletal and **cardiac** muscle

Question 35

raised **CK** raised **aldolase** deleted dystrophin

Answer 35

duchenne musclar dystrophy

Question 36

becker and duchenne inheritence

Answer 36

X linked recessive | myotonic dystophy - AD

Question 37

AR secondary arthritis 2nd 3rd MCP chondrocalcinosis liver disease skin hyperpigmentation DM central hypogonadism cardiomyopathy

Answer 37

hereditary haemochromatosis | excessive GIT iron absorption