BRS- Metabolism Flashcards
____ diseases are only seen in males.
____ are more severe in males.
XR- only males
XD- more severe in males
Gene pair inherited entirely from the same parent is called ____?
uniparental disomy
Gene defect expressed solely based on the sex of the parent passing on the defective gene
genomic imprinting
Chromosome deleted in both Prader Willi and Angelmans
chromosome 15, 11q
Three abnormalities of morphogenesis
- intrinsic abnormality ?
- mechanical forces?
- destructive forces?
- intrinsic: malformation
- mechanical: deformation
- destructive: disruption
Two causes of low AFP
- trisomy
- overestimated GA
Causes of high AFP:
- NTD
- MFG
- underestimated GA
- abdominal wall defect
- edema/skin abnormality
Triple mark screen levels in Down Syndrome?
- low AFP, estriol
- High hCG
At what time in pregnancy are CVS and Amniocentesis performed?
- CVS: 10-13 weeks
- Amniocentesis: 16-18 weeks
Marfans:
- inheritance pattern
- chromosome
- gene
- AD
- chromosome 15
- fibrillin
Marfans:
skeletal findings
- tall
- long fingers
- decreased U/L segment ratio
Marfans:
most common cardiac and ocular findings
- upward lens subluxation
- aortic root dilatation
Management of Marfans:
- Bbers + sport avoidance to prevent aortic dissection
- endocarditis prophylaxis
- ophthalmic exams
Physical appearance of Prader Willis
- FTT –> short + obese
- fish mouth, almond eyes
Prader Willis Neuro effects
- retardation
- hypotonia
- learning/behavior disorder
GU abnormalities assc with Prader Willis
-small penis/testis
-hypogonadism
+/- cryptorchidism
Into late childhood/ adulthood, what complications are assc with Prader Willis?
- OSA
- CVD
- DM2
Angelman Syndrome neuro features
- jerky movements, ataxia
- inappropriate laughter
- mental retardation
Angelman Syndrome physical appearance
- small head/ big mouth
- blond hair/ blue eyes
Male version of Turners Syndrome? _____
Assc chromosome _____
Noonans
chromosome 12
Appearance of Noonans patient
- short, webbed neck
- shield chest
- low hairline
- hypertelorism
Two heart defects assc with Noonans
- right sided lesions
- pulm stenosis
Two disorders assc with chromosome 22q11
- DiGeorge
- velocardiofacial syndrome
What does CATCH 22 stand for?
- cardiac anomaly
- abnormal face
- thymic hypoplasia
- cleft palate
- hypocalcemia
- 22 chromosome
Describe thymic abnormalities seen in DiGeorge
-no thymus/parathyroid=
immunodeficiency, hypocalcemia
Complication assc with hypocalcemia
- tetany
- seziures
Cardiac effect assc with velocardiofacial syndrome
- VSD
- right sided arch
Neuro findings in velocardiofacial syndrome
- hypotonia
- perseverative behavior
Collagen type assc with Ehlers Danlos? OI?
- ED: type V
- OI: type I
ED:
skin & joint findings
- skin and joint hypermobility
- tissue paper thin scarring
CV and GI findings in ED
- rectal prolapse
- MVP
- aortic dilatation
- fragile vessels
Osteogenesis I:
- describe eyes/teeth/ears
- describe knee position
- blue eyes, gray blue teeth, hearing loss
- genu valgum
List the VACTERL assc
- vertebral defects
- anal atresia
- cardiac anomalies (VSD)
- TE fistula
- renal defects
- limb defects
List the CHARGE assc
- colobomas
- heart defects
- atresia of the nasal choanae
- retardation
- genital anomalies
- ear anomalies
Williams syndrome:
chromosome
gene
inheritance pattern
- chromosome 7
- elastin
- AD
Williams syndrome
- appearance
- neuro
- elfin facies
- cocktail party personality, retardation
Williams syndrome
cardiac and endocrine findings
- supravalvular AS
- idiopathic hypercalcemia
Cornelia de Lange Syndrome
-appearance
- single eyebrow
- short stature
- microcephaly
Synophrys describes
single eyebrow
Cornelia de lange neuro sx
- MR
- hypotonia
Russel Silver Syndrome:
appearance
- short
- assymetric skeleton
- triangle face
- café au lait spots
Pierre Robinson main symptoms
- micrognathia
- cleft lip and palate
- tiny airways= otitis and URI
Cri du Chat:
- chromosome
- appearance
- neuro
- short arm chromosome 5
- small head, hypertelorism
- cat like cry, MR
What is the incidence of Downs Syndrome
1:660
Second most common trisomy + predominant sex
trisomy 18; females
Three features obvious in newborn with trisomy 18
- scissoring
- rockerbottom feet
- clenched hands w/ overlapping digits
Trisomy 18 is assc with _______ defects of the head
midline
holoprosencephaly, cleft lip palate, microphthalmia/single eye
Life expectancy in trisomy 13,18
18: 1 year
13: 1 month
Cause of Turners Syndrome + incidence
- single X
- 1:2k
Key finding assc with Turners
- ovarian dysgenesis/ pubertal delay
- aortic coarctation
Four facial features assc with downs
- brachycephaly
- epicanthal folds
- brushfield spots
- protruding tongue
MSK features of downs
- wide space between first and second toes
- single palmar crease
- clinodactyly
Four GI features of Downs
- duodenal atresia
- omphalocele
- hirschsprungs
- pyloric stenosis
- celiacs
Most common cardiac defects seen in downs
endocardial cushion defects
Two diseases seen later in life assc with downs
- ALL
- ALZ
Sensory defects assc with Downs
-hearing/vision defects
Endo defect assc with Downs
-hypothyroidism
Most common inherited cause of retardation?
Fragile X, CGG repeats
What is large in fragile X?
ears
testes
Most common cause male hypogonadism
Klinefelters, XXY
Klinefelters features
- tall
- hypogonad
- gynecomastia
- antisocial behavior
Define rhiso/meso/acromelia
- rhiso: proximal long bone short (humerus, femur)
- meso: medial (ulna, tibia)
- acro: distal (hands, feet)
Most common skeletal dysplasia
- achdondropalsia
- AD
- FGFR3
- paternal age
Craniofacial abnormalities in achondroplasia
- megalencephaly
- foramen magnum stenosis
- risk cord compression
- hearing loss (conductive)
Skeletal findings in achondroplasia
- rhizomelia
- lumbar kyphosis –> lordosis
- tident hands
Fetal alcohol syndrome:
- FTT
- smooth philtrum
- MR
- cardiac defects
Folic acid dosage to prevent NTD
-4-8g/day
Risk of CHD in general population
-1%
Fetal phenytoin syndrome
- MR
- cardiac
- nail, digit, facial abnormalities
Drug assc with phocomelia
thalidomide
Signs of IEM:
- seizures
- developmental delay/FTT
- vomiting
Family history factors related to IEM
- consanguinity
- neonatal deaths
- MR
- unusual dietary preferences
Labs for IEM
- metabolic acidosis
- hyperammonemia
Elevated ammonia suggests what disorders
Elevated urine reducing substances suggest
Ammonia: urea cycle
Urine reducing substance: galactosemia
Homocystinuria cause
Cystathionine synthase deficiency
Homocystinura = Marfans except
Hypercoagulable state
No aortic dilatation
Increased methionine
+urinary cyanide nitroprusside
Treatment for homocystinuria
- met restricted diet
- aspirin
Transient tyrosinemia also involves elevated ______.
It lasts ______.
________ decreases tyrosine levels.
Phenylalanine
1 month
Vitamin C eliminates
Cystinuria is failed reabsorption of what amino acids?
COLA
- cystine
- ornithine
- lysine
- arginine
Hartnups Disease:
Cause
Symptoms
Failure of transport of neutral amino acids
Rash, MR, ataxia
Transient hyperammonemia lasts how long?
Symptoms?
- 24-48 hours of life
- alkalosis –> coma
MC urea cycle deficit
Inheritance pattern
Ornithine transcarbamylase
XR
Ornithine Transcarbamylase Def labs (3)
High ornithine, orotic acid
Low citrulline
Cause of Galactosemia + two key symptoms
G1UDPiciency
Hepatomegaly
Hypoglycemia
After newborn first feeds
Renal/ocular findings assc with galactosemia
RTA
Cataracts with oil droplet appearance
Finding in females with galactosemia
Ovarian failure
Cause of death in galactosemia patients
E. coli sepsis
Deficiency assc with fructose intolerance
F1P aldolase B
Glycogen storage disease two key findings
Organometallic
Metabolic acidosis
Von Gierke cause
Pompes cause
VG/ I: G6P
Pompes/ II: a-glucosidase
Which Glycogen Storage Disease is assc with hepatocellular carcinoma
Von Gierke
Classic lab findings assc with fatty acid oxidation defects
Nonketotic hypoglycemia
Hyperammonemia
Two clinical outcomes assc with fatty acid oxidation defects
Cardiomyopathy
Myopathy
Most common fatty acid oxidation disorder
Medium chain acyl CoA dehydrogenase
When should mitochondrial disorders be suspected
- atypical presentation
- 3+ organ systems involved
What does MELAS stand for?
Mitochondrial encephalopathy lactic acidosis strokes
How to diagnose mitochondrial disorders
Tissue samples
Tay Sachs + Guachers are what type of disorders
Lysosomal storage
Gauchers deficiency
Tay Sachs deficiency
Neimann-Pick deficiency
Metachromatic leukodystrophy deficiency
Tay Sachs: hexosaminadase A
Gauchers: glucocerebridase
Neimann Pick: sphingomyelinase
Metachromatic leukodystrophy: arylsufatase A
Gauchers & Tay Sachs & Neiman Pick:
Common feature
Distinguishing feature
All have cherry red macula
Gauchers & Neiman Pick: HSM
Neiman Pick: ataxia
Key feature of juvenile onset Tay Sachs
Cherry red macula is absent
Key finding in infantile Tay Sachs
Hyperacusis
MSK finding assc with gauchers
Erlenmyer flask shaped distal femur
Metachromatic Leukodystrophy:
Life expectancy
10-20 years
Thickened cranium
J shaped sella turcica
Beak life vertebrate
Called?
Dysostosis multiplex –> characteristic of mucopolysaccharidoses
What are the four mucopolysaccharidoses
Hunter
Hurler
Sanfilippo
Morquio
A-iduronidase deficiency is assc with what mucopolysaccharidosis?
Hurler
Hurler key symptoms
Corneal clouding
Coarse facial features
How to diagnose hunters and hurlers syndrome
Heparin and dermatan sulfate in the urine
Inheritance hunters vs hurlers
Hunters: XR
Hurlers: AR
How is morquio different from other mucopolysaccharidoses?
No Mental retardation
–> scoliosis & cor pulmonale
Porphyria pattern
Episodic and participated
Porphyria clinical presentation
- burgundy colored urine
- colicky abdominal pain
- autonomic instability
How to diagnose porphyrias
Increased serum and urine porphobilinogen
Wilson’s disease
Inheritance pattern
+ symptoms
AR
- Kayser Fleischer rings
- Hepatic dysfxn
- Neuro changes
Menkes kinky hair syndrome
- Inheritance pattern
- abnormal lab
- PE findings
- XR
- low copper, ceruloplasmin
- seizures, pale kinky friable hair
