Genetic disorders and inborn errors of metabolism

Question 1

genomic imprinting

Answer 1

expressed solely based on sex of parent passing on defective gene ~ 11q of 15 -> angel man or trader-willi

Question 2

maternal markers

Answer 2

alpha feto protein- incr with neural tube defects, multi gestation, fetal demise, underestimated gestational age, ventral abd wall defects
triple marker: nAFP, unconguated estriol, beta-HCG. down= low AFP, low estriol, high beta-hcg. all 3 low= trisomy 18

Question 3

cvs

Answer 3

10-13wks. kayotype, DHA extration, enzym eanalysis

Question 4

amniocentesis

Answer 4

16-18wks. sloughed fetal cells.

Question 5

percutaneous umbilical blood sampling

Answer 5

hematologic abn, genetic d, infection, fetal acidosis. used to arm med or blood transufsion to fetus

Question 6

common genetic D

Answer 6

marfan syndrome, prader willi, angelman, noonan, digeorge,ehler danlos, osteogenesis imperfecta, VACTERL association, CHARGE, Williams, Cornelia de Lange, Russell silver syndrome, pierre robin syndrome, cri du chat syndrome,

Question 7

marfan syndrome

Answer 7

AD. CT D. C15-fibrillin
affect: ocular, CV, skeletal
P: tall, elongated extremitis/ fingers, j laxity, chest wall deformities (pectus excavatum), scoliosis or kyphosis. decr upper to lower segment ratio. upward lens subluxation and retinal detachemnt (need regulr ophthalmologic exam), aortic root diation, aortic dissection. aortic regurg
Dx: clinical. need r/o homocystinuria
C: endocarditis (prophylax), sudden death-dissection, HTN,

Question 8

prader willi

Answer 8

P: almond eyes, fish like mouth. FFT, short, small feet. hypotonia, MR, hypogonadism
Dx: FISH
C: hypotonia- poor sucking. obesity- obstructive sleep apnea, cardiac disease, DM2, psych

Question 9

angelman

Answer 9

C: jerky arm mV, ataxia. small wide head, large mouth, prognathic, blood hair blue eyes

Question 10

noonan syndrome

Answer 10

= male turner. AD. C12
P: short, shield chest. short webbed neck and low hairline. right sided heart lesion~ pul valve stensis (turner has left sided heart lesion), MR in 25%
Dx: clinical

Question 11

DiGeorge and celocardiofacial syndrome

Answer 11

AD or sporadic. C22q11 deletion. CATCH-22
Cardiac anomaly, abn facies, thymic hypoplasia, cleft palate, hypocalcemia (sz), C22.
digeorge: short palpebral issues, chin/ear anomalies, to, VSD, AA anomalies,
vekicaruifacuak: cleft palate, promiennt nose with square nasal root, fish mouth, short chin, VSD, right sided AA, hypotonia, learning D, preservative behavior.
Dx: FISH

Question 12

ehlers-Danlos sydnrome

Answer 12

AD. defective type V collagen
Phyperextensible J -dislocation and scoliosis, loos/fragile skin (minor laceration = major wounds that heal poorly with broad atrophic tissue paper thin scars), MV prolapse, aortic root dilation, fragile vessels= bruise easily, constipation, real proposal hernia
dx- clinical
C: aortic dissection, GI bleeding

Question 13

osteogenesis imperfecta

Answer 13

abn type I collagen
P: blue sclerae, fragile bones, yellow or gray-blue teeth, easy bruisability
dx: clinical and decr tpye I syn in fibroblast
C: early conductive hearing loss, skeletal deformity 2/2 fractures

Question 14

VACTERL association

Answer 14

vertebral defects, anal atresia, cardiac anomalis -VSD, TE (tracheoesophageal fistula), renal, limb defects (hypoplasia, syndactyly),
dx- clinical

Question 15

CHARGE

Answer 15

sporatic colobomas, heart defect-tog,, atresia of nasal choanae, retardation, genial anomalies, ear

Question 16

williams

Answer 16

AD. C7- elastin.
P: cocktail party personality. elfin facies, MR, loquacious, supravalvular aortic stenosis, idiopathic hypercalcemia in infancy, CT abn- hoarse voice, hernia
dx- FISH

Question 17

Cornelia de lange

Answer 17

sporatic> AD
P: single eyebrows (cynophrys), short, no skeletal abn, SGA. FFT, microcephaly, downturn upper lip, micrognathia, infantile hypertonia, MR, small hands/ft, cardiac defect, autistic behavior, no expression, self destructive
dx-clinical

Question 18

Russell silver syndrome

Answer 18

short, skeet asylum, normocephalic, SGA

Question 19

pierre robin syndrome

Answer 19

micrognathia, cleft lip and palate,
dx clinical
C: recurrent otitis media, upper airway obstruction

Question 20

cri du chat syndrome

Answer 20

C5-arm delation. sporadc
catlike cry, microcephaly, MR.
dx-deletion, clincal

Question 21

down syndrome

Answer 21

epicentral skin folds, brachycephaly, protruding tongue, hypotonia, clinodatyly, wide space btw 1st and 2nd tow, duodenal atresia, hischsprong, pyloric stenosis, cardiac-40%
C: atlantoaxial cervial spine instbaility, leukemia, celiac, alzheimer, obstructive sleep apnea, hearing loss, hypothyroidism, cataracts, glaucoma, refractive error

Question 22

trisomy 18

Answer 22

F>M
MR, hypertonia, scissoring of LE, delicate small facial features, clenched hands, overlapping digits, rocker botton feet
95% die

Question 23

trisomy 13

Answer 23

midline defect. holoprosencephaly, severe MR, microphthalmia, single eye, cleft let or palate.
die

Question 24

turner

Answer 24

1X
P: short, webbed neck, shield chest, welling of dorm hands and ft, ovarian dysgenesis-delay puberty, cardiac defect-left sided, coarctation, hypothyroidism

Question 25

fragile X

Answer 25

CGG | P: large ears, macrocephaly, blue irides, large testes, autistic / ADHD features

Question 26

Klinefelter

Answer 26

XXY. most common male hypogonadism and infertility P: tall, long extremities, hypogonadism, delay puberty bc lack testosterone, gynecomastia, variable IQ, behavioral findings

Question 27

skeletal dysplasia

Answer 27

group of inherited disease with short stature caused by bone growth abn achondroplasia- most common type

Question 28

achondroplasia

Answer 28

AD. FGF-3R. incr with paternal age rhizomelia= long bone abn= short humerus and four AD. megalencephaly, foramen magnum stneosis, frontal bossing, lumbar kyphosis in infant becoming lumbar lordosis, bow legs, trident shaped hands. otitis media, conductive hearing loss C: foramen magnum stenosis lead to hydrocephalus or cord compression- SID obstructiv esleep apnea

Question 29

potter's

Answer 29

severe oligohydramnios, fetal compression, limb abn, potter facies

Question 30

amniotic band syndrome

Answer 30

rupture of amnionic sac, wrap around fetus cause scaring and amputation

Question 31

fetal alcohol syndrome

Answer 31

SGA, microcephaly, FTT

Question 32

phenytoin syndrome

Answer 32

MR, cardiac, growth retardation, nail abn, wide anterior fontanelle, low hairline,

Question 33

inborn errors of metabolism

Answer 33

together 1:5000. suspect if ill, non responsive to tx, unexplained sz, dev delay, FTT, persistent V, labs inconsistent with P onset: acute severe neonatal illness (classic P). recurrent intermittent epi at times of stress, chronic progressivee sx (usually mito D) Fx: neonatal death, parental consanguinity, MR

Question 34

odor v IEM

Answer 34

mousey/musty- PKU sweet maple syrup- maple syrup urine disease sweaty feet- isovaleric or glutamic academy rotten cabbage- hereditary tyrosinemia

Question 35

AA metabolism defects

Answer 35

homocystinuria, PKU, hereditary tyrosinemia, maple syrup urin disease

Question 36

homocystinuria

Answer 36

AR. cystathionine synthase def. P: marfanoid body habits wo arachnodactyly, downward dens subluxation( marfan is upward), hypercoag, CV abn, scoliosis, dev delay dx: incr methionine in urine and plasm. pos urine cyanide nitroprusside test tx- methionine restricted diet, asprin decr TE, folic acid and B6 sup

Question 37

transiet tyrosinemia of newborn

Answer 37

prematture infant on high protein diet lethargic, asx tx: vit C self limited

Question 38

PKU

Answer 38

AR | P: dev delay, hypotonia, mousy odor, MR

Question 39

maple syrup urine disease

Answer 39

AR. P: commit, hypotonia, coma, dev delay, hypoglycemia, acidosis, dx: serum and urine branched chain aa tx: dietary protein restriction- -if start w'in 2wks of life avert neuro damage

Question 40

tyrosinemia type I

Answer 40

AR P:peripheral neuropathy, liver disease, rotten fish or cabbage odor, renal tubular dysfunc Dx: succinylacetone in urine tx: restrict phenylalanine, tyrosisn, NTBC. liver transplant die

Question 41

membrane transport defects

Answer 41

cystinuria- AR, renal stones, UTI, dysuria, urinary freq | hartnup- AR, asx, ataxia, photosensitive rash, MR

Question 42

urea cycle defect

Answer 42

ammonia >200. toxic to brain and liver. sx: poor feeding, hyper vent, behavioral changes,s sx, ataxia, coma transient hyperammonemia of newborn- self limited, in premie, in 24-48hr of life, aggressive tx of hyperNH3 needed to prevent neuro sequelae ornithine transcarbamylase def- most common urea cycle defect.t x-linked. begin at onset of protein ingestion= vomit, lethargy, coma, dx-elevated urine orotic acid, decr serum citrulline, incr ornithine, liver bx tx- low protein diet and hyperammonemia,

Question 43

carbohydrate meta

Answer 43

galactosemia hereditary fructose intolerance, glycogen storage disease

Question 44

galactosemia

Answer 44

AR. galactose-1 phosphate uridyltransferase def. suspected in any newborn with hepatomegaly and hypoglycemia P: begin after cow's milk --> V/D/FTT, hepatic dysfunction, cataracts, oil droplet appearance, renal tubular acidosis dx: nonglucose reducing substance in urine. confirm enzyme def in RBC, prenatal screen tx: galatose pree diet, prog- normal IQ if tx early. ovarian failure, death in early infancy from e coli sepsis if not tx

Question 45

hereditary fructose intolerance

Answer 45

fructose 1 p adolase B def. fruit

Question 46

glycogen storage disease (GSD)

Answer 46

organomegaly and metabolic acidosis 1) von gierke's disease (GSD type 1): G6P def. hypoglycemia, hepatomegaly, hypertriglyceridemia, enalrge kidney. need high complex carb diet. risk for HCC 1: pope's disease (GSD type 2): alpha glycosides def: muscular weakness, cardiomegaly, preset in 2wk with flaccid weakness, poor feeding, hepatomegaly

Question 47

fatty acid oxidative defect

Answer 47

present during acute illness or fasting when FA are used. nonketotic hypoglycemia, hyperammonenemia, myopathy, cardiomyopathy. medium chain acyl-CoA deH def= most common D tx: high carb low fat diet, carnation sup

Question 48

mitochondrial D

Answer 48

suspect in common disease has atypical presentation or disease involve 3+ organ systems. Kearns sayre syndrome (ophthlamoplegai, pig deign, hearing loss, heart block, neuro deign). MELAS. dx base on tissue bx- abn mito

Question 49

lysosomal storage disease

Answer 49

gangliosidose (tay sachs, caucher's, neimann pick, metachromatic leukodysptrophy), mucopolysaccharidoses (glycosaminoglycan accumulate in multi organ, short stature, mR, dysostosis multiplex, oar shaped ribs, breaklike vertebrae, hurler syndrome, hunter syndrome, sanfilippo, morquio),

Question 50

tay sach

Answer 50

AR. hexosaminidase A def. | incr startle, hyperacusis, macrocepahly, cherry red macula, sever dev delay, blindness,

Question 51

gaucher's

Answer 51

glucocerebrosidase def- most common gangliosidosis. AR. erlenmeyer flask shape to distal femur. die by 4yo

Question 52

niemann pick

Answer 52

sphingomyelinase def. neuro degen, atazia,sz, heptaosplenomegaly, cherry red macula. die by 4yo

Question 53

hurler syndrome

Answer 53

most severe mucopolysaccharidosis. AR. progressive coarsened facial feature, corneal clouding, dx: dermatan and heparan sulfate in urine, tx- early bone marrow transplant 10-15y life

Question 54

hunter syndorme

Answer 54

x-linked R. P: hepatosplenomeglay, hearing loss, papule over shoulder, dy hunter needs sharp eyes therefrore no corneal clouding

Question 55

porphyrias

Answer 55

defect in heme pig biosynthesis skin photosensitivity and neuro and abdominal sx. personality change, emotion lability , weakness, colicky abd pain, autonomic instability, dark burgundy urine. dx: incr serum and urine porphobilinogen tx: IV glucose, correct electrolyte abn, avoid fasting and precipitating drugs

Question 56

wilson's disease

Answer 56

dx: decr serum ceruloplasmin. elevated serum and urine copper

Question 57

menke kinky hair disease

Answer 57

x lined R. low serum copper, pare kinky friable hair,