Genetic Disorders Flashcards
Lipid disorderassociated with pancreatitis
Familial hyperchylomiron Mia
And anytime trigglerides >1000
Dyslipidemiaassociated with palmarxanthomas
Familialdysbetalipoproteinemia
Statins
InhibitHMG-COAreductase.
For cholesterol - use fibrates for triglycerides
Von girke disease
G6PD deficiency
Fasting hypoglycemia, hepatomegaly, high lactate,cholesterol, tris, uric acid
Infants
Poor growth, doll face,distended ab.
Seizure coma deathdisabilityrelated to severe and recurrenthypoglycemia
Good px w/ t x
Pompedisease
Lysosomal acid a-glucocisdase
Hypotonia, weakness cardiomegaly, mortality
Classic- infancy
Macroglossiaweakness hypotonia . hypertrophiccardiomyopathy hepatomegaly 2’ heart failure
Elevated ck = muscle damage
Cori disease
Debranching enzyme a-1,6- glycosidesdeficiency
Like g6pd but milder s normal lactate.
May showmusclesx
Mcardle disease
Exercise intolerance, myoglobinuria,muscle cramps,second wind phenomenon
Glycogen storagediscase genes
All autosomal recessive
Tay sacks gene enzyme substrate
Hexosaminidsase A
GM 2 ganglioside
Ashkenazi s Cajun and French Canadian
Tay sacks symptoms
Progressive neuro
Infancy
Cherry red spotmacula
2-3 year mortality
No repatosplenomegily
Neumann pick path
Sphingomyelinase
Siphingomgelin
Ashkenazi
Niemann pick clinical
Prog neuro
Cherry red spot
Hepatosplinomegaly
Type A infants early mortalit y
Type B later childhood no neuro early adult mortality
Typ c variable onset early adult mortality
Gaucher disease path
Glucocerebrosidase
Glucocerebroside
Ashkenazi
Gaucher, disease clinical
Anemia
Thrombocytopenia
Bone problems
Hepatic splenomegaly
Gaucher (foam) cells in bm
Tx enzyme replacement
Fabry disease path
X- linked recessive
a -galactosidase A
Ceramide trihexosidas
Fabry disease clinical
Renal
Cv
Peripheral neuro
No sweat
Angiokeratomas
Hurler syx path
a-L-iduronidase
He paran and dermatansulphate
Mucopolysacdarideosis
Hurler Syx clinical
Dev delay
Coarse faces
Airway obstruction
Corneal clouding
Hepatosplenomegaly
Cv cause of death childhood
Hunter syx
Mild Er hurler deathadolescene
Aggression
No corneal clouding
Iduronate-2-sulfat ase
He paran and dermatan sulfaate
X linked recessive
Fructose and galactose metabolismdisorders genetics
All autosomarecessive
Aldolase - B deficiency
Hereditary fructose intolerance
Fructose -1-paccumulation
Hypoglycemia seizures gi upset repatomegulyjaundice cirrhosis failure to thrive
Tx avoid fructose
Fructokinase deficiency
Essential fructosuria
Usually asymptomatic
Galt deficiency
Classic galactosemiia
Aka uridydyl transferase
Galactose-1-paccumulation
Similar consequences and presentation as hereditary fruetose intolerance
Risk of e col i sepsis.
Cataracts
Tx no galactose mainly dairy
Galactokinase deficiency
Mild
Early life cataracts
Congenitalerythropoeitie porphyria
Anemia andphotosensitiveskin
Uroporphyrinoger 3 synthase
Erythroporiticprotoporphyria
Childhood
Painful non-blisteri Ng photosensitivity
Anemia
Gallstones
Acute intermittent porphyria
Ab pain
Tachycardia
Peripheral and motor neuron s x - pain, numbness, tingling weaknessprogressive upper to lower
Depression
Port wine urine
Exacerbated by p450 induces
PorphyriaCutaneatarda
Chronic blistering
Elevated hepatictransaminases
Often dt spontaneousnon-hereditarymutations
Acute intermittent porphyria enzyme
Porphobilinogen deaminase
Quad screendown’s
Msafp and estriol low
B-hcg and inhibin A high
Quad screenedward’s
All low
Edward’s syx
Trisomy 18
Severe intellectual disability
Micrognathia
Overlapping fingers
Low ears
Congenital heart defects
Renal defects
1 year mortality
Pata u syx
Trisomy 13
Severe intellectualdisabiity
Cutis aplasia
Microcephaly
Cleft palate
Polydactyl
Umbilical hernia
Congenital heart defects
Renal defects
1 year mortality
Heart defects Turner’s
Bicuspid aortic value
Aortic coarctation
Cause trinucleotide repeat expansion
DNA polymerase slippage
Tendency to detach from template when encounteringexcess repeats
Huntington’sgenetics
CAG repeat >40
Disease possible>35 repeats
Protein polyglutami nation
Myotonic dystrophy type I genetics
CTG >50 DMPK 3’ UT R
Toxic RNA accumulation
Friedrich ataxiagenetics
GAA >100 chromosome 9 frataxin intron
Decreased gene expression
Autosomal recessive
Fragile x genetics
CGG >200 FMR1 5’ UTR x chromosome
Promotor methylation and silencing
X dominant
Friedrich ataxiadlinical
Muscle weakness
Loss vibratory sense
Diabetes
Hypertrophic cardiomyopathy
Kyphoscoliosis
Fragile x denial
Intellectual disability
Autism
Macro-orchidism
Prader will i syx
Floppy baby sy.x
Hypotonia → failure to thrive and feedingdofficulties
Progresses tohyperphagia and associatedobesity and diabetes in later childhood and adulthood
Moderate intellectualimpairment
Learning disability
Hypoojonadism
Angelmansyx
Moderate intellectual disability
Seizures
Minimal speech
Ataxia
I appropriate laugher
Prader will i genetics
Paternal microdeletion 15q11-q13
Or maternal uniparental disomy
Angelman genetics
Maternal microdelation 15q11-q13
Or paternal uniparentedisomny
Ivacaftor
Cftr agonist
Cf t x
Lumacaftor
Improves conformational stability of f508 mutation and this trafficking of mature CF TR proteinto cellsurface
Used in combotherapy with ivacaftor for Cf
Most common Cf mutation
Delta- f508
Diagnostic test Cf
Qpit
= sweat test
Screening test Cf
IRT
cleft lip/palate risks
spontaneous - most
FHx
DiGeorge - 22q11.2
Patau - tri13
Edwards - tri18
Pierre Robin sequence
congenital micrognathia
glossoptosis - posterior displacement or retraction
cleft palate
can obstruct airway, difficulty swallowing/suckling
mostly SOX9 mutations
choanal atresia
failed dev of choana in nasal sinuses
difficulty breathing through nose
in infants (obligate nose breathers), cyanosis feeding, improves crying (mouth breathing)
Tet spell
tetralogy of fallot
cyanosis when crying/agitated
improves with squatting
TEF
tracheal esophageal fistula
failure of trachea to fully separate from esophagus during development
embryonic stage wk 4-7
often associated with:
- vertebral defects
- anal atresia
- cardiac tefects
- renal abnormalities
- limb anomalies
complications immediate after birth:
- drooling/choking
- respiratory distress
- aspiration pneumonia
- feeding difficulties
secondary causes pulmonary hypoplasia
oligohydraminos
- IUGR
- Potter sequence - renal malformation
SOL
- diaphragmatic hernia
- enlarged heart
abnormal diaphragmatic activity “practice breathing”
- CNS
- NMJ
CDH
congenital diaphragmatic hernia
diaphragm hole –> bowels in chest, usually left side
often –> pulmonary hypoplasia
“can’t miss”
respiratory distress at birth
bochdalek hernia
CDH Back Left
morgagni hernia
CDH anterior Right
signs severe CDH
- cyanosis
- respiratory failure
- scaphoid abdomen (sunken)
- barrel chest
- bowel sounds in chest
- pulmonary hypertension
later complications CDH
infants/later childhood:
- lung infection
- obstructive lung disease
- GERD
- recurrent hernia
21-hydroxylase deficiency
congenital adrenal hyperplasia
low mineralocorticoids
low glucocorticoids
high androgens
in girls: virilization, ambiguous genitals
salt wasting
11ß-hydroxylase deficiency
low glucocorticoids
high mineralocorticoids
high androgens
hypertension
hypo-K
girls: virlization, ambiguous genitalia
17a-hydroxylase deficiency
low androgens
high mineralocorticoids
high glucocorticoids
hypertension
low K
boys: lack of virilization, ambiguous genetalia; severe: phenotypically female
Marfan’s
fibrillin-1 defect - component of microfibrils that surround elastin fibers
long thin extremities, lose joints, long fingers
cause of death:
- aortic root dilation/dissection/rupture
- spontaneous pneumothorax
- other cardiovascular complications
EDS
group of disorders
collagen formation/structuring
skin and joint hypermobility
cause of death: aortic rupture, etc.
homocystinuria
cysathionine synthase deficiency
high circulating homocysteine
marfanoid habitus
risk of premature atherosclerotic CV disease
osteogenesis imperfecta
type I collagen (bones)
low bone mass
fragility fractures
blue sclera
dental anomolies
hearing loss
causes of 46XY–> F phenotype
most common: androgen insensitivity syx (androgen R mutation)
17-a-hydroxylase deficiency (also causes hypertension and hypo-K)
