8/10/2019 Bosch Review 1

1/13

DON'TPEEK

2013

GENETIC

DISORDERS

REVIEW

r

Part

1

Barbara .Bosch,

M.D.

8/10/2019 Bosch Review 1

2/13

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/

J

't,re

g4y'1sa

2013 GeneticDisordersReview

Part 1; BarbaraD. Bosch, \,i.D.

page

2

References or USMLEStep 1-format

questions with

modifications):

Catalano .

Appleton

&

Lanqe

Review f General

Patholoqv,

rh

d. McGrawHillMedical, 003.

Fenderson A,StrayerDS,RubinR, RubinE. lllustrated &AReview f Rubin'sPatholoqv,"d

ed. Lippincot t i l l iams Wilk ins, 011.

Goldberg . LanqePractice estsUSMLEStep1,

2nd d. McGrawHillMedical, 006.

Kettering D, FletcherHM. PreTestMicrobioloqv,

2rh d. McGrawHillMedical,

007.

KingMW. Lanqe

Q&A

USMLE tep1,6'n d. McGraw

il lMedical ,008.

KlattEC, KumarV- Robbins

nd Cotran

Review f Patholoqv, 'ded. Saunders lsevier, 01 .

KleinRM, EndersGC. PreTest natomv.Histoloov Cell

Bioloqv, 'd

ed.

McGraw

HillMedical, 007.

Le TT,

KleinJ, Shivaram . FirstAid

Q&A

or he USMLE

Step1. McGraw

HillMedical, 007.

Le T, KrauseK, Klein

J,

Shivaram

. FirstAid

Cases or he USMLEStep1. McGrawHillMedical,

2006.

MufsonM. PreTest

Pathophvsioloqv,'ded.

McGrawHillMedical, 005.

PreTest

Clinical

iqnettesor

he USMLEStep

1. 4th d. McGrawHillMedical, 008.

A

36

year-old

woman

gives

birthat 34 weeks'

gestation

o a male nfantwho ives or

onlyan hourafier

delivery.On

physical

xamination,he nfant s at

the 30'n

ercentile

or height

nd

weight.

Anomalies

include icrocephaly,

cleft

ip

and

palate,

nd

postaxialolydactyly,

withsixdigits neachhand nd oot.Which f he ollowing

karyotypess most ikelyo be

present

n his nfant?

A. 45,X

B. 46,XY

c.

47,XXY

D.

47,XY,43e'

E. 47,XY,+18

F. 69,XXY

8/10/2019 Bosch Review 1

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2013

GeneticDisorders

Review Part1 Barbara

D. Bosch,M.D.

page

3

Patau

yndrome

tr isomy

3;

47,XX,+13r 47,XY,+13)

-

f7

*.\t.

5

ro-\L

'-f'""A"' lo^

-

-'Jh*'

J,lt'L

o

risk ncreases ith

Eglemalage

.

usually ausedby meiotic ondisjunction

.

clinicalindingsnclude

everemental

etardation,

left

ip &/or

palate,

proboscis, icrocephaly,tructural Jedgeeg andpolydactyly

oftenassociated ith

cardiac nd renalanomalies,

s wellas

holoprosencephaly

nd rocker-bottomeet

very

poor

prognosis

ue

o

severemalformations

A 4 month-oldmale nfant

s witnessed aving seizure

nd s brought

o the emergency

oom. His moth

indicates

hathe has

been istlessor he

past

ew days

and hasalsovomited

few imes.

The nfanthasa

protuberantbdomenwith hepatomegaly,s wellas thinextremities. loodwork evealshat he nfant s

hypoglycemic.n

addition, is blood

pH

s

slightly cidicwitha reduced

evel

of bicarbonate. lood

chemistryurther eveals

levatedriglycerides.Which

of the ollowing

isorderss most

ikely n this

oatient?

A. Hurler yndrome

B.

McArdle yndrome

C. Pomoe

isease

D. Tay-Sachs

isease

E. von Gierke

isease

-

A liverbiopsy

n this

patient

willmost ikely eveal ecreased

ctivity

f which

of

the ollowing

nzymes?

A. acidmaltase

B.

glucose-G-phosphatase

C.

glycogen

ynthase

D. hexosaminidase

E.

pyruvate

inase

8/10/2019 Bosch Review 1

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2013 enetic

Disorders

eview-

part

1;Barbara

. Bosch,M.D.

page4

Von Gierke

disease

autosomal

ecessive)

.

type

I

q 99gCtSlaGgC.dlSCeS.e

ue to

a deficiencyof

gtucose-6-phosphatase

.

clinicalindings

nclude epatomegaly

ue o excessive

lycogen,

hortstature nd

poor

growth

.

Iaboratory

tudiesshow

severe

asting

hypoglycemia

which

can

cause eaturessuch

as

irritability,

eizures,

pathy, ypotonia, nd even

coma),

acticacidemia

hyperlipidemia,

nd

hyperurlqemia

+

d"*l

s.lon.r

o

definitive

iagnosismade

by enzyme nalysis

W?

"n

//*

*

,2vaC,../q.

A 27

year-old

man

comes o the

physician

or an nfertility ork-up.

He

and hiswifehave

been r ying o

conceive

child or 6

years.

On

physical

xamination,he

patient

s noted o

be tall

6

t.,5 in.).

He also

exhibits

ilateral

ynecomastia

nd reducedesticular lze.

A semen

analysis eveals

ligospermia.

Laboratorytudies emonstratencreased erum evelsof follicle-stimulatingormone nd slightly

decreased

evels

f testosterone.What

s the mostcommon

ause

of this

patient's

hromosomal

abnormality?

A.

expansion

f a trinucleotideepeat

B. isochromosomeformation

C. meiotic

ondisjunction

'

D.

nonreciprocal

ranslocation

E. ring

chromosomeormation

Which

of the ollowing

aryotypes

s most ikely o be

present

n this

man?

A. 46,X,i(Xq)

-

f,,,e.-,

.

B. 46,XYdel(22q111

0tgnyt

c. 47,XXY

D. 47,XYY

E. 48,XXYY

hko

^nJk'

t"'g,

l"{

-gyry

8/10/2019 Bosch Review 1

5/13

/1,xxyy

a^

a[ro

o**

l,

G"l

y*7

"-=.

Klinefelter

yndrome

.

most commonkaryotype:

47,XXY

.

usually aused

y meiotic ondisjunction

. frequent auseof malehypogonadism

o

clinicalindings

nclude n elongated odywith

a eunuchoid

habitus,emale

distributionf hair,high-pitchedoice,

2013 Genetic

DisordersReview Part'1;

BarbaraD. Bosch, Vl.D.

page

5

x t

r t a

F i {

b

t i

l r

i a

s F

i ; r t

{

t

? / : t ,

l ,

r

l t

* t s

: l :

: :

r a

Frontrl

baldnc:s

LJ(

ca+tt{

. ,

gynecomastia,

nd testicularatrophywith infertility

ue

r"tt

)t"tYLl

toolisosoermia

J

.

characterized

v owserum evels f testosterone

nd

elevated

J

serum evels

f follicle-stimulatingormone

FSH),

uteinizing

ihlinl

lettr|c|].t

l.

Srov

L\ er

chrll hri$

aL

n4ffione

(LH)

nd stradiol

dcre ;pn:elt

F{xn1e.t}'lx

p bi.lnjr

A 25

year-old

oman

comes o the

physician

omplaining

f frequent osebleeds,

ecurrent

one

pain

and ncreasing

bdominal

irth.

Physical xaminationeveals

marked epatosplenomegaly.

complete

blood

ountshows

pancytopenia.

adiologictudies emonstrate

everal adiolucent

onedefects.A

bonemarrow

iopsy eveals

nlarged ellscontaining fine ibrillary

material eminiscent

f crumpled

tissue

paper.

This

patient

most ikely

arries

mutations

n he

gene

hatencodeswhich

of the ollowing

types

of hydrolytic

nzymes?

A. acid

B-glucosidase

,

B. acidmaltase

C.

galactosidase

D.

glucose-6-phosphatase

E. hexosaminidase

F.

neuraminidase

G. sphingomyelinase

Snlxll

tc ticulnt

sire

^1,"

[$l

ebseA*"'L*

8/10/2019 Bosch Review 1

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2013Genetic

Disorders

Review Part

1;

BarbaraD. Bosch,M.D.

page

6

Gaucherdisease

autosomal

ecessive)

.

*

mostcommon ysosomal torage

isorder

glucocerebrosidesprimarily

n

the macrophage

mononuclear

phagocyte

ystem)

characterizedy markedly nlarged

macrophages

ith ibrillarycrumpled

tissue

paper"

ytoplasm

Gaucher

ells), specially

rominent

n the:

-

spleen

d

marked plenomegaly

pancytopenia

bone

marrow

+

bone

pain,

deformities

nd skeletalractures

-

liverand ymphoidissue

+

hepatomegaly

nd ymphadenopathy

threevariants:

*

type

-

most requent nd mildest ariant

especially

revalent

n Jewsof

European escent);

resents

n adulthood

ith

eatures

s described

above; ela tively ormal ifespan

type l

-

rareand mostsevere ariant;

resents

n infancywith

eatures s

described bovePLUS

perivascular

erebral

nvolvement

neuronal

degeneration;eads o death

n infancy r early

childhood

type ll

-

intermediateariant;ypically

resents

n adolescence;hortened

lifesDan

diagnosismadeby measurementf enzyme

ctivity

A 25

year-old

manwitha history f autism nd

mental etardations seenby a

genetic

ounselor.

he

man s noted o havean elongatedace,

protruding

arsand

macroorchidism.

is maternal ncle s

similarly ffected.What s the most ikely

underlying ause

of this

patient's

enetic

isorder?

A. chromosomalondisjunction

B.

chromosome

nversion

C. expansion f trinucleotideepeat -

D. frameshiftmutation

E. missensemutation

F. mitochondrial NAmutation

G. nonreciprocalranslocation

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