Congenital D/O p2 - MPS, Mitochondrial, peroxisomal, cutaneous, and Other

Question 1

Hunter vs. Hurler memory tools

Answer 1

Hunters need eyes to shoot and intelligence to hunt (no eye involvement, less severe ID)
Gargoyles “hurl” balls of fire (hurler has gargoyle facies)

Question 2

MPS common features

Answer 2

Growth retardation, short stature (all but San Fillipo)

Question 3

Hurler’s Syndrome (MPS 1) enzyme

Answer 3

alpha - L - iduronidase (“L” in Hurler)

Question 4

Hurler’s Syndrome (MPS 1) sx

Answer 4

Severe ID, skeletal dysplasia
hearing loss, corneal clouding
macroglossia, visceromegaly
valvular cardiac disease

Question 5

Hurler’s Syndrome (MPS 1) path

Answer 5

zebra bodies

Question 6

Hunter’s Syndrome (MPS 2) inheritance, enzyme

Answer 6

X-linked
iduronate sulfatase
hunTer – enzyme with Ts

Question 7

Hunter’s Syndrome (MPS 2) sx

Answer 7

Nodular ivory colored lesions back, shoulders, upper arms
Like hurler but no corneal opacities (macrocephaly, ID, hoarse voice, hearing loss)
entrapment neuropathies

Question 8

Sanfilippo’s syndrome (MPS 3) lab

Answer 8

elevated urine heparan sulfate

Question 9

Hunter & Hurler product lab

Answer 9

elevated urine dermatan and heparan sulfate

Question 10

Sanfilippo’s syndrome (MPS 3) sx

Answer 10

primarily cognitive, fewest physical abnormalities

primarily ID, + sz, mvt d/o, behavioral prob –> severe dementia

Question 11

Morquio’s syndrome (MPS 4) gene

Answer 11

GLB1

Question 12

Morquio’s syndrome (MPS 4) sx

Answer 12

Normal intellect
Short, skeletal dysplasia, respiratory compromise
cardiac valvular abnormalities, corneal clouding
spinal cord compression

Question 13

MELAS gene

Answer 13

MTTL1

Question 14

MELAS full name

Answer 14

mitochondrial encephalopathy, lactic acidosis, and strokes

Question 15

MELAS sx

Answer 15

migraine, vomiting with anorexia, growth retardation
weakness with exercise intolerance
Stroke like episodes with residual sx (progressive neuro probs, cognitive regression, encephalopathy)
Progressive deafness

Question 16

Leigh syndrome ws

Answer 16

Apneas, sighs, periodic hyperventilation, irregular breathing
infant: hypotonia, vomiting, sz, myoclonic jerks
>1yo: cbl atax, dysarthria, spastic, chorea/dystonies
Peripheral neuropathy, autonomic failure
Ophthalmoplegia, nystagmus

Question 17

Leigh syndrome MRI

Answer 17

BL symmetric T2 hyperintense BG, SN, inf. olivary nuc, PAG, CC

Question 18

Leigh syndrome tx

Answer 18

some thiamine responsive forms exist

Question 19

Kearns sayre sx

Answer 19

mitochondrial DNA deletion myopathy
Progressive ophthalmoplegia (can be only sx)
pigmentary retinopathy
ataxia
cardiac conduction probs

Question 20

Kearns-sayre path

Answer 20

Muscle with ragged red fibers

WM spongy myelinopathy

Question 21

Refsum inheritance, target

Answer 21

AD

Peroxisomal

Question 22

Refsum sx

Answer 22

periph neuropathy, anosmia, cbl signs
Short 4th metatarsal
cardiomyopathy, skin changes
retinitis pigmentosa –> night blind, visual field

Question 23

Refsum lab

Answer 23

increased phytanic acid

reduced/absent peroxisomes

Question 24

Zellweger’s gene

Answer 24

PEX

Question 25

Zellweger's sx

Answer 25

Most severe peroxisomal disorder hypotonia, decreased reflexes, sz, bad ID Arthrogryposis SN hearing loss, cataracts, retinal :( High forehead, lg fontanelles, flat supraorbital ridge, hypotelorism, epicanthal folds, flat nasal bridge, micrognathis Liver cirrhosis, polycystic kidney chondrodysplasia punctate

Question 26

Zellweger's imaging

Answer 26

Lg ventricles, periventricular "pseudocysts" | Pachy/polymicrogyria

Question 27

NF1 chromosome, gene, inheritance

Answer 27

Chr 17 Neurofibromin gene AD

Question 28

Hypomelanosis of Ito sx

Answer 28

hypopigmented streaks at birth on lines of blaschko ID, sz, small/big head Eye prob, cleft lip/palate, skeletar hemi-hypertrophy Congen heart (TOF)

Question 29

Hypomelanosis of Ito imaging

Answer 29

Hemimegalencephaly/lissencephaly | cerebellar hypoplasia

Question 30

Osler-Weber-Rendu AKA

Answer 30

hereditary hemorrhagic telangiectasia

Question 31

Osler-Weber-Rendu gene, enzyme

Answer 31

HHT1/2 | Endoglin

Question 32

Osler-Weber-Rendu sx

Answer 32

Telangiectasias all over (skin, mucosa, retina, GI tract) AVMs in CNS Recurrent epistaxis common

Question 33

Xeroderma Pigmentosum chromosome, dysfunction

Answer 33

chr 9 | abnormal DNA repair

Question 34

Xeroderma Pigmentosum sx

Answer 34

UV light sensitive --> freckling multiple cutaneous and systemic tumors Neuro - progressive cog dysfxn, hearing loss, tremor, chorea, ataxia, peripheral neuropathy

Question 35

Incontinentia Pigmenti inheritance, gene

Answer 35

X-linked Dominant (female only) | NEMO

Question 36

Incontinentia Pigmenti sx

Answer 36

Vesicles at birth --> verrucous ~6wk --> hyperpigmentation on Blaschko lines. Become hypopigmented or atretic later in life Poss normal neuro, or ID, pyramidal abnl, ocular abnl

Question 37

NF 2 chromosome, gene, inheritance

Answer 37

Chr 22 Merlin gene AD

Question 38

Lesch Nyhan gene, enzyme

Answer 38

HPRT1 | hypoxanthine guanine phosphoribosyl transferase (HGPRT)

Question 39

Lesch Nyhan sx

Answer 39

motor delay, progressive rigidity with dystonia, choreoathetosis, sz aggression, self mutilation Milder form with no neuro sx, just hyperuricemia, gout, nephrolithiasis

Question 40

Lesch Nyhan lab, tx

Answer 40

Hyperuricemia | purine restricted diet, allopurinol (decreases uric acid)

Question 41

Acute Intermittent Porphyria enzyme, dysfunction

Answer 41

porphobilinogendeaminase (PBGD) | dysfunction in heme production

Question 42

Acute Intermittent Porphyria sx

Answer 42

onset after puberty attacks abd pain with n/v/d, fever, tachycardia Motor/axonal peripheral neuropathy prox>distal, UE>LE Radial nerve classically involved decreased DTR Severe can impact bulbar and respiratory

Question 43

Fragile X mutation, gene

Answer 43

CGG trinucleotide repeat | FMR1

Question 44

Rett syndrome inheritance, gene

Answer 44

X linked | MECP2

Question 45

Rett syndrome sx

Answer 45

hand wringing, stereotypies, hand/fist in mouth arrest head growth, severe ID sz, spasticity, scoliosis dysautonomia with apneas

Question 46

Menkes disease inheritance, gene, defect

Answer 46

X linked ATP7A Defect copper transport intestine and blood-brain barrier

Question 47

Menkes disease sx

Answer 47

hypotonia, hypothermia, severe DD, sz cerebral vasculopathy --> bleed, subdurals Brittle coarse light hair, full cheeks Bony prob (osteoporosis, bony dysplasia, metaphyseal dysplasia, spontaneous bone fractures)

Question 48

Menkes disease lab

Answer 48

low serum copper | low serum ceruloplasmin

Question 49

Williams syndrome mutation

Answer 49

Microdeletion chromosome 7

Question 50

Williams syndrome sx

Answer 50

Elfin facies, ID, very verbal, friendly with strangers diabetes, supravalvular aortic stenosis hearing loss, hyperacusis elevated calcium

Question 51

Cri-du-chat mutation

Answer 51

microdeletion chr 5 | Un, deux, trois, cat, sank

Question 52

Cri-du-chat sx

Answer 52

microcephaly, high cry wid spaced eyes, epicanthal folds, mandib hypoplasia VSD severe ID, hyperactive, aggressive, repetitive behaviors

Question 53

Friedreich's Ataxia mutation, gene, chromosome

Answer 53

trinucleotide repeat GAA Rataxin gene Chr 9

Question 54

Friedreich's Ataxia age of onset

Answer 54

5-15yo

Question 55

Friedreich's Ataxia sx

Answer 55

Neuro: Irregular gait, limb ataxia, loss proprioception/vibration, UMN signs, optic nerve atrophy Skeletal (scoliosis, high arched feet) Cardiac (conduction abnl, HCM)

Question 56

Machado-Joseph Disease AKA

Answer 56

SCA 3

Question 57

Machado-Joseph Disease mutation, gene, chromosome

Answer 57

CAG trinucleotide repeat ATXN gene Chr 14

Question 58

Machado-Joseph Disease sx

Answer 58

progressive ataxia OR dystonic rigid form | Bulging eyes, ophthalmoplegia, tongue atrophy, facial fasciculations, amyotrophy

Question 59

Hallervorden-Spatz enzyme, mechanism

Answer 59

``` Pentathenate Kinase (PANK2) Iron accumulation --> neurodegen ```

Question 60

Hallervorden-Spatz sx

Answer 60

episodic dystonia, facial grimace, dysphagia, poss spasticity Pigmentary retinopathy, optic atrophy, retinal degeneration

Question 61

Joubert Syndrome sx

Answer 61

dvlp delay, ataxia, oculomotor apraxia, hypotonia Irregular respiratory (apneas, irreg patterns) Blindness (retinal disease) Renal failure

Question 62

Joubert syndrome MRI

Answer 62

Molar tooth sign | Cbl vermis hypoplasia, lg 4th ventricle, abnl sup cbl peduncles

Question 63

Miller-Dieker syndrome gene

Answer 63

LIS1 (can also cause isolated lissencephaly)

Question 64

Miller-Dieker syndrome sx

Answer 64

Dvlp delay, spastic, sx Microcephaly, micrognathia, low ears, short upturn notes, thin lip Bitemporal hollowing, prominent forehead