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Cheng-Ching > Peds > Flashcards

Peds Flashcards

1
Q

inborn errors metabolism

A

energy metabolism/catabolism-present acutely

intoxication - Sx free then present acutely - urea cycle

complex molecules/anabolism - not acute presentation

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2
Q

Galactosemia

A

-Galactose-1-P UDT deficiency MCC - classic galactosemia w/ intellectual disability
AR, GALT/GALK/GALE genes ; newborn screen,
-present at birth, vomiting, diarrhea, jaundice; cataracts b/c galactitol
Dx: reducing substances in urine
-Tx: no lactose (can’t break down), no galactose (no cataract, hepatomegaly but still CNS Sx)

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3
Q

PDH deficiency

A

PDH: oxidative decarboxylation: pyruvate to Co2 + acetyl CoA
-low lactate:pyruvate ratio, elevate lactate ad pyruvate; buildup alanine
-neonatal acidosis, lactic acidosis or present later
ataxia
-can trigger exacerbations by high card meal
-cytic lesions: white matter BG +/- corpus callosum

-MCC X-linked E1 (less common AR)

Tx: acetyl CoA, ketogenic diet, carnitine, coQ10, biotin, acetazolamide-ataxia

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4
Q

NF1

A

Diagnostic criteria: 2 or more:
-6 cafe au lait
-inguinal/axillary freckling
-2 cutaneous neurfibromas or 1
-plexiform neurofibroma - (Schwann cells, fibroblasts; peripheral nerves - can come from DRG + invade spinal cord; GI track-intestinal hemorrhage ; can be malignant)
-2 Lisch nodules
-Optic path glioma - anywhere along tract - low grade (can present precocious puberty) ; serial imaging over time
-bony lesion (sphenoid wing dysplasia, thinning bone cortex)
-child of parent with NF1

mild developmental delay
-renal A stenosis from renal A dysplasia-> HTN
-pheochromocytoma
-Moyamoya syndrome
-cerebral ansuerysms
-macrocephaly independent of hydrocephalus
-pathologic fracture, scoliosis, sphenoid wing dysplasia
Cafe au lait,

autosomal dominant neurofibromin- chr 17 - variable expression, complete penetrance

DDx Legius syndrome - SPRED1 gene AD - cafe au lait and axillary/inguinal freckling but no Lisch nodules, no other NF findings
NF1-tumor suppressor-regulates RAS proto oncogene - can get astrocytoma, leukemia

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5
Q

GLUT-1 deficiency

A

-GLUT1 encoded by SLC2A1 de novo or ADDeVivo syndrome
low CSF glucose, normal serum glucose
-epileptic encephalopathy if early, or episode invoultary movements/ataxia, paroxysmal exertional dyskinesias
-Tx: ketogenic diet

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6
Q

Phenylketonuria PKU

A

Phenylalanine hydroxylase deficiency (phenylalanine to tyrosine); -if tetrahydrobiopterin deficiency (cofactor of phenylalanine hydroxylase)
-accumulate phenylalanine —> metabolized phenylacetic acid causing musty odor
autosomal recessive
-normal at birth after feedingrise phenylalanine levels; early normal Neuro development
-no acute metabolic encephalopathy
-microcephaly, seizures, fair with blond hair/blue eyes - no tyrosine and no melanin pigment production
-avoid phenylalanine

-newborn screen: detects hyperphenylalanemia-high phenylalanine in blood
Dx: reduction phenylalanine in blood and urine after BH4 given
Tx: low protein, phenylalanine free diet

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7
Q

Maple syrup urine disease

A

autosomal recessive
-branched chain a-ketoacid dehydrogenase complex deficiency (leucine, isoleucine, valine)

I Love Vermont maple syrup from maple trees
(with B1ranches). - Isoleucine, Leucine, Valine
decreased branched-chain α-ketoacid dehydrogenase (B1). Causes increased α-ketoacids in the blood, especially those of leucine.

-with feeding, present as neonate
Day 2-3 of life - progressive encephalopathy
opisthotonus arched back posture (like an arched tree)
Urine: maple syrup, esp during exacerbations
Tx: low protein diet

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8
Q

X linked disorders

A

All Oblivious Females Can Pass Her Boys X-Linked Disorders

All-Aicardi (dominant) + X-linked adrenoleukodystrophy (ABCD1); acqueductal stenosis

Oblivious-ornithine
transcarbamylase deficiency ; oculocerebrorenal syndrome - OCRL1 (-Lowe syndrome )

Females-Fabry + Fragile X (trinucleotide repeat)

Can/Kan-CMTX ; KAllman’s; Kinky hair syndrome - Menkes (ATP7A Copper transporter); Kennedy disease (spinobulbar muscular atrophy-CAG repeat in androgen R)
CDKL5

Pass -PDH deficiency (MCC), pigmentia (incontinentia-pustular lesions-NEMO), periventricular nodular hetertopia (FLNA), Pelizaeus-Merzbacher

Her ett-Hunter (Hurler AR)
RETT - MECP2

Boys-BPAN-beta propeller protein associated neurodegernation (mostly female)

X-Linked-McLeod’s syndrome-XK disease+ Lesch-Nyhan + XL Lissencephaly (DCX)

Disorders-muscular Dystrophy (Emery-Dreifuss-Emerin mutation, Becker, Duchenne)

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9
Q

Neurulation
Differentiation
Specification

A
  1. neuralation (3-6 wks) - Neural plate - ectoderm ->to neural tube via notorcord (mesoderm “make note”)
  2. Notochord - mesoderm becomes vertebral column
    -induces neuralation neural plate - forms midline groove with fusion starting in center,->
    by week 4: anterior neuropore then posterior closes
    ->3. neural tube formed-> differentiation
    -ventral: notorcord signals via sonic hedge hog
    -dorsal: lateral ectoderm signals
  3. 5-6 wks - Specification: Neural tube->3 vesicle segmentation
    -Prosencephalon = telencephalon (cerebral hemispheres) + diencephalon (hypothalamus, thalamus)
    -Mesencephalon - midbrain
    -Rhombencephalon - pons, medulla, cerebellum

-Specification problem - septo-optic dysplasia

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10
Q

Neural crest cells

A

PNS , autonomic ganglia+ cromaffin cells adrenal medulla + melanocytes

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11
Q

neural tube defects-anterior

A

NTD: risk: more common in females, retinoids, VPA, carbamazepine? , hx infant NTD
-supplement 0.4 mg folate
-Dx: prenatal US, alpha-FTP +Achesterase elevated (in serum+amniotic fluid); can get prenatal MRI; if positive screen for trisomy 13 and 18 (encephalocele)

-anencephaly (no cerebral hemispheres, cranial vault b/c no mesoderm diffferentiation), Anterior neuropore prob

-encephalocele (hernation neural tissue into midline skull-occipital (more severe, more common)>frontal; fluntuant mass, can still live but microcephaly) -anterior neuropore
-trisomy 13, 18

Holoprosencephaly:
-no prosencephalon to telencephaphon (cerebral hemispheres + BG+ olfactory) + diencephalon (thalamus+hypothalamus)
-no telencephalon to 2 cerebral hemispheres + BG
-alobar -most severe; vs semilobar vs arrhinecephaly

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12
Q

Holoprosencephaly

A

Trisomy 13, 18, Sonic HH, cholesterol synthesis (Smith Lemli Opitz-7 dehydrocholesterol reductase)
ALobar- cyclopia, endorine problems, hydrocephalus

semilobar -partial agenesis corpus callosum (commissural plate); splenium + genu preserved)

Arrhinecephaly - agenesis olfactory bulb + tract
-Kallmann’s X linked dominant - anosmia + hypogonadims

-septo-optic dysplasia - Specification problem -HESX1, homeobox, SOX endocrine deficiency, no septum pellucidum, hypoplastic optic nerve
+/- arrhinencephaly, hypothalamic hamartomas
-ataxia

cavum septum pellucidum - normal

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13
Q

neural tube defects - posterior

A

-meningocele (only leptomeninges, CSF herniate) vs occipital encephalocele ; no neurological deficit vs myelomeningocele

Myelomeningocele - SC, nerve root, meninges protrude, Chiari II ; hydrocephalus, bowel/bladder dysfunction

-sacral agensis- absence sacrum, not sacral SC ; range clinical Sx
-GI, urogenital, SC prob
-maternal IDDM risk
-homeobox gene mutations, AD

Diastematomyelia - splitting SC into 2 by midline septum

-diplomyelia - duplication of SC - two central canals each with gray and white matter like a normal SC (vs diastematomyelia)

Posterior neuropore prob - spina bífida
-occult spinal dysraphism - tuft of hair + neuro dysfxn - tethered cord, epidermoid cysts

spinal bifida occulta - no neuro dysfxn

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14
Q

tuberous sclerosis complex

A

TSC1 mutation on chromosome 9 or TSC2 mutation on chromosome 16. (1 Hamartin for 9 or 2 Tuberin for 16 on sale) - sporadic - form TSComplex which inhibits mTOR pathway
Tumor suppressor genes. Autosomal dominant, variable expression.
RAPAMYCIN (mTOR inhibitor)
HAMARTOMAS
-Hamartomas in CNS, lymphangiomyomatosis, retina, skin-mulberry lesion
-hamartomas - not malignant and don’t grow; make of abnormal cells - T2 hyperintense hazy patches on MRI; correlate with neuro deficits; TX with rapamycin
-Angiofibromas+fibrous cephalic plaque ; ungual fibromas
-Mitral regurgitation
-Ash-leaf spots +Shagreen patches (raised)
-can see under Wood’s lamp UV light
-cardiac Rhabdomyoma-can regress over time
-autosomal dOminant;
-Mental retardation (intellectual disability);
-renal Angiomyolipoma
-Shagreen patches (connective tissue hamartomas),
-dental enamal pits

-Subependymal giant cell astrocytomas - specific for TSC, low grade; surgery curtative; or Tx Rapamycin
-ENHANCE vs calcified nodules

-subependymal nodules - hyperdensity on CT scan; calcified; can grow
-don’t correlate with intelligence or seizures vs cortical hamartomas

-MCC infantile spasms - vigabatrin
-burden tubers correlates with seizures
-angiomyolipomas

lymphangiomyomatosis -pulmonary disease in females >males- dyspnea, hemoptosis, pneumothorax - Tx - tamoxifen-fatal yrs after under; Dx chest imaging

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15
Q

Fabry

A

only x-linked sphingolipidosis
alpha galactosidase defect
‘Fabry is a gal (galactosidase) who tries ceramics’
(build up of ceremide trihexaside)
Throwing pottery (hands+feet on pedal-small fiber neuropathy) + splatter (angiokeratomas trunk, LE) + round clay clogging arteries->strokes (dolioectatic) + cardiomyopathy + ESRD + cloudy corneals

-ESRD, birefringent lipid deposits, lamellar deposits
Tx: enzyme replacement alpha galactosidase

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16
Q

propionic acidemia - branched chain organic acidemia

A

AR, deficient propionyl-CoA carboxylase
-accumulate propionyl-CoA+glycine; normal MMA levels
-makes D methylmalonyl CoA from propionyl CoA; (then Methylmalonyl-CoA mutase makes succinyl coA for Krebs)
need biotin B7 as cofactor
-normal at birth; episodic hyperammonemia
-movement disorders - BG involved
-pancytopenia, bleeding, ICH
-on newborn screen
Tx: biotin, carnitine; ABx-metronidazole - decrease propionate by gut bacteria

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17
Q

methylmalonic acidemia

A

Methylmalonyl-CoA mutase deficiency
-makes succinyl-CoA->Krebs cycle
-B12 cofactor
-present first week life

-ketoacidosis, hyperglycinemia, hyperammonemia, elevated MMA in blood and urine ( vs propionic acidemia)
Tx: low protein, can respond to B12, carnitine, ABx to reduce gut flora propionic acid

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18
Q

Lesch Nyhan

A

deficient hypoxanthine guinane phosphoribosyltransferase - purine metabolism salvage (HPRT1 gene)
-accumulate purines - increase uric acid
-choreoathetoid movements, gout, nephrolithiasis

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19
Q

Niemann Pick

A

sphingomyelinase deficiency->accumulate sphingomyelin
(cherry Pick the liver, knee on a springboard)
AR
-type A: severe, infant, cherry red spot
Type B - visceral - no CNS effects; Hepatosplenomegaly + interstitial lung disease
Bone marrow biopsy: foam cells

Type C: NPC1- Chr 18
-cholesterol trafficking problem;
+ Filipin test - unesterified cholesterol accumulates in lysosomes
-fibroblasts can’t esterify cholesterol
-EOM abnormalities

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20
Q

metachromatic leukodystrophy

A

snowman without arms + legs + egg on head
-cerebroside sulfate buildup
Arylsulfatase A deficiency
-late infantile, juvenile, adult
-confluent white matter spares U fibers
-

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21
Q

Chiari I vs II, III
Dandy Walker

A

I - cerebellum+tonsils displaced -
-if <1 cm displaced, Pt can be ASx
-brainstem Sx, Ha, ataxia, syringomyelia (separate from central canal, lined by gliotic tissue)
-2/2 posterior fossa hypoplasia - overcrowding?

II = Arnold Chiari-vermis + myelomeningocele
-hydrocephalus-4th ventricle compressed
-Tx: shunt, suboccipital crani

Chiari III - cerebellar heniation into cervical/occipital encephalocele

syringomyelia - pressing on central canal
vs hydromyelia - central canal enlarged, lined by ependyma

Dandy Walker: Agenesis of cerebellar vermis leads to CYST enlargement of 4th ventricle
-chromosomal abnormalities
-facial hemangiomas
-noncommunicating hydrocephalus, spina bifida.

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22
Q

Sialidosis

A

glycoproteinoses - lysosomal storage disorder-deficient alpha-N-acetyl neuraminidase

-AR
-Type I - adolescent- cherry red spot + myoclonic epilepsy - no dysmorphism
Type II - kids - cherry red spot + myoclonic epilepsy + coarse facial features, psychomotor retardation
neonatal form - hydrops fetalis

Tx: -increased urinary excretion sialic acid containing oligosaccharides
-vacuolated lymphocytes, membrane bound vacuoles

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23
Q

Joubert’s syndrome

A

ciliopathy ->resp problems

molar tooth sign
-cerebellar vermis hypoplasia
ataxia, developmental delay, EOM abnormal
-central apnea
-renal failure
+/- Leber’s congenital amaurosis-rod/cone dystrophy

vs COACH syndrome - Molar tooth + LIVER + PUPIL problems
-cerebellar vermis hypoplasia, oligophrenia, congenital ataxia, coloboma (blotchy pupil), hepatic fibrosis

vs. Leber congenital amaurosis-can get molar tooth

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24
Q

Progressive myoclonic epilepsies

A

All AR - Tx VPA except for MERRF
1. Unverricht-Lundborg - EPM1 gene - cystatin B - BALTIC SEA
-severe myoclonus

  1. Lafora body - EPM2A/2B encoidng laforin, malin protein
    Partial seizures, dementia
    Dx: skin biopsy
  2. MERRF
    -deafness, lipomas, optic atrophy, myopathy, neuropathy, severe myoclonus
    -elevated lactate levels
    -no VPA
  3. Neuronal ceroid lipofuscinosis - CLINGY FAT and CLINGY TP over eyes (blindness), head (dementia), struggling to break free ->seizures/facial dyskinesias as adults + bits of deposits intraneural
    blindness, dementia, psychomotor retardation, +/- myoclonic seizures + intraneuronal deposits
    CLN1 - PPT1 - infantile - saposins A/D
    CLN2 - TPP1 - late infantile
    CLN3-Juvenile - 4-10 yrs
    -Adult - 30s - dementia, facial dyskinesias

microscopy: lymphocyte vacuolation; fingerprint bodies +other deposits accumulate

  1. Sialidosis - NEU1 - NEW FARM SILO CHERRY SPOT
    Type 1: no alpha-neuraminidase
    -adolescence/adult - normal cognition
    -ataxia, GTC, vision loss , cherry red spot

Type 2 - deficient alpha-N-acetyl neuraminidase/Beta-galactosialidase
-fundus changes, cherry red spot, neuropathy, dysmorphism, severe myoclonus

(shaky ataxic alcoholic farm hand with fetal alcoholism=dysmorphism)

Dx: urinary sialyl oligosaccaride + leukocyte enzyme deficient
-lymphocyte vacuolation

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25
Q

congenital aqueductal stenosis

A

btw 3rd + 4th ventricle
(foramen of Monro-lateral+3rd)
1. neurulation disorder -abnormal midbrain development
2. X linked - gyria +/- holoprosencephaly/Chiari II
2. CMV, mumps
3. tumors: ependymomas, hamartomas - or secondary compression on aqueduct

Sx: macrocephaly, sundowning of eyes, hydrocephalus

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26
Q

Peroxisomal disorders

A
  1. Zellweger’s - PEX mutation (Pachy Poly PEX)-AR
    -chondrodysplasia, calcific stippling patella, dysmorphic faces, normal head circumference, liver/kidney disease, hearing loss
    -pachygyria/polymicrogyria; white matter involved
    Dx: -VLCFA in serum, decreased RBC plasmalogens, decrease hepatic peroxisomes
    -die early
  2. neonatal adrenoleukodystrophy - NO pachygyria
    +heterotopia, cerebellar dysplasia, spares U fibers
    -cirrhosis, adrenocortical atrophy
    -VLCFA in serum
  3. infantile Refsum’s - phytanic acid increased
    A dominant PHYTING the REF; punching in chest (cardiomyopathy); socks and gloves on-neuropathy
    AD Autosomal dominant;
    -motor delay, hearing loss, anosmia,
    retinitis pigmentosa
    -cardiomyopathy
    -large fiber neuropathy (vs KSS-no neuropathy)
    -short 4th toes
    -mild, can live to adult
    -no peroxisomes
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27
Q

Stroke in young

A

Hereditary hemorrhagic telangiectasia+Osler-Weber-Rendu - autosomal dominant - multiple AVMs
pseudoxanthoma - thrombosis
Ehlers-Danlos - aneurysm, dissection
Fabry - ectasia, thrombosis
MELAS-infarcts not correlating with vascular territories

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28
Q

xeroderma pigmentosum

A

peripheral neuropathy, ataxia, hyperkinetic, cog decline

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29
Q

adrenoleukodystrophy

A

XL ABCD1 gene - peroxisome membrane transport

  1. childhood onset cerebral type - 4-8 yrs
    ADHD behavior problems, aggression
    -spasticity, incoordination, bulbar dysfxn
    -no pachygyria; SPARES U fibers
    -rim of enhancement posterior white matter - differentiate (except Alexander’s - contrast enhancement on MRI)
    -neonatal adrenoleukodystrophy - NO pachygyria
    -heterotopia, cerebellar dysplasia
    -cirrhosis, adrenocortical atrophy
    -adrenal cortex, Leydig cells testis
    -brain biopsy: perivascular cuffing, +T cells
    -risk adrenal crisis
    -die early
  2. adrenomyeloneuropathy-age 20, sensory neuropathy, sex dysfxn, sphincter control problem, peripheral nerve demyeliantion, no inflammation
    -can have adrenal insufficiency
    -female carriers mild Sx
  3. pure adrenal insufficiency
    -Addison crisis

elevated VLCFA, elevated ACTH 2/2 adrenal insufficiency

Tx: Lorenzo’s oil - 4:1 glyceryl trioleate-glyceryl triercate - if young + ASx
BW transplant

30
Q

Leigh’s

A

subacute encephalomyelopathy-mitochondrial dysfxn from respiratory chain
-sporadic or familial, maternal inheritance; mutation in mitochondrial/nuclear DNA encoding resp chain subunits
-onset within 1 year: hypotonia, loss of head control, poor suck, vomiting, myoclonic jerks
-onset >1 year: respiratory prob, apneas, periodic hyperventilation, nystagmus, ophthalmoplegia
-lactate elevated in blood+CSF; lactate + pyruvate elevated during exacerbations

-hyperintense BG, substantia nigra, inferior olive, periqueductal gray

Tx: thiamine, if responsive better prognosis

31
Q

Kearns Sayre

A

Usually sporadic - mitochondrial DNA deletion or duplication

KISS- eyes half closed, not moving, heart stops, ataxic, short

HIGH PROTEIN in CSF
opthalmoplegia + onset <20 + short stature/pigmentary retinopathy/cerebellar ataxia/heart block/ increased CSF protein
-pacemaker b/c heart block
-no neuropathy vs Refsum
path: ragged red fibers in muscles, white matter with spongy myelopathy

32
Q

congenital disorders of glycosylation

A

AR
Type I CDG - abnormal glycan synthesis- developmental delay, liver problems, ataxia, retinitis pigmentosa, stroke like episodes, hypogonadism,

carbohydrate deficient transferrin -serum+CSF

lipodystrophy: fat pads in buttocks, inverted nipples
Dx: serum transferrin isoforms
Tx: supportive

33
Q

cortical development

A
  1. cerebral hemispheres : single epithelial layer around lateral ventricles-> ventricular zone; radially oriented
  2. marginal layer forms above ventricular zone; subventricular below
    -radial glia in ventricular zone sends processes to pia cortex surface and new neurons migrate on scaffold made by radial glia to cortical plate

-marginal zone: Cajal-Retzius cells-express Reelin, for migration

  1. cortex forms inside out - cells migrating earliest form deepest layers first
    -neuronal progenitor cells: ventricular, subventricular zones

-radial glia toward cortical plate-neurons migrate

neuronal cell: pyramidal, stellate /cortical granular, Betz (5th layer motor cortex)

glial cells: astrocytes, oligodendrocytes, ependyma, microglia

all 6 layers of cortex by 27 wks gestation
-peak migration 12-20 weeks
gyri, sulci: 20-36 wks

-most cortex neocortex (isocortex) = 6 layers
[vs. primitive cortex - fewer layers - archicortex - hippocampus; paleocortex - olfactory, limbic]
Layer I - most superficial - pia covers-molecular layer
II - external granular cell
III - external pyramidal cell - corticocortical efferents (project to II and III layers)
IV-internal granular cell
V-internal pyramidal cell (Betz) - corticostriate
VI - multiform overlies white matter - corticothalamic (cortex to thalamus)

Thalamic efferents: thalamus to cortex - I, IV, VI

pyramidal cells - III and V: glutamatergic-largest + cortical neurons
stellate/granular neurons-II and IV- smaller interneurons

33
Q

Corpus callosum dysgenesis

A

commissural plate-bridge over which axons run ; problems = corpus callosum dysgenesis/agenesis
-Aicardi, nonketotic hyperglycinemia
-hypertolorism
-coronal MRI: racing car sign

34
Q

Phakomatoses/neurocutaneous disorders of ectoderm

A
  1. Neurocutaneous melanosis - leptomeningeal melanoma + giant hair pigmented nevi, congenital melanocytic nevi; risk melanoma
    -from melanoblasts origin in pia matter)
    -brain base, brainstem, cerebellum
    -hydrocephalus
  2. Parry Romberg - hemifacial atrophy - loss facial tissue, cartilage, bone, hair (ROMBERG fall TO ONE SIDE - hemifacial)
    -HA, Horner’s, seizures, hemiparesis
    -DDx scleroderma, lipodystophy
  3. Maffucci’s - enchondromas (cartilage tumor) and hemangiomas - vitiligo, hypergimentation
    -CNS tumors, compression by enchondromas
  4. Incontinetia pigmenti - vesiculobulous lesions at birth, verrucous lesions 6 weeks, HYPERpigmented lesions following Blaschko lines of skin development
    -NEMO gene mutation-encodes protein in NF k B pathway (sounds like fish species name)
    -X linked
    - +/- neuro delay
  5. VHL - retinal, cerebellar, spinal hemangioblastoma - renal cell carcinoma, no skin findings
    -AD mutation on VHL gene chromosome 3 - tumor suppressor protein
  6. Hypomelanosis Ito - hypopigmented streaks following skin lines (Island of Ito - have to look for it in a map)
    -cataracts, macrocephaly+eye abnormalities seizures,
    -lissencephaly, hemimegalencephaly
    -detect lines with UV light
  7. epidermal nevus syndrome -types include Proteus syndrome (asymmetry; hypertrophy soft tissue + bones), Becker nevus (high plague, breast hypoplasia, rib defects)
    others: sebaceous, phakomatosis pigmentokeratotica, CHILD syndrome
    -nevi over face predict CNS involvement; can get hemimegalencephaly ipsilateral to facial nerve nevus +contralateral hemiparesis ; other cortical development problems
    -risk malignancy -basal cells carcinoma, risk astrocytoma
    -iris colobomas
35
Q

Glycine encephalopathy/
Nonketotic Hyperglycinemia

A

hiccups in utero, myoclonic jerks
-present within hours of birth, irritable, poor feeding, hiccups
burst suppression EEG + hypsarrhythmia
-agenesis corpus callosum
-can’t break down glycine - defects in the genes (GLDC P proteinand AMT) that encode glycine cleavage enzyme system resulting in decreased enzyme activity
-enzymes = AR (proteins, membrane transporter AD)

-high glycine in CSF;
CSF/plasma glycine concentration >0.6

36
Q

cortical malformations

A

proliferation: focal cortical dysplasia; megalencephaly
-Focal cortical dysplasia: dysmorphic enlarged cells, balloon cells, abnormal lamination
+/- tuberous sclerosis

migration: lissencephaly, periventricular nodular heterotopia, pachygyria, subcortical band heterotopia

organization: polymicrogyria (NOT migration), schizencephaly, microdysgeneiss, focal cortical dysplasia with normal cell types

37
Q

microcephaly/macrocephaly

A

microcephaly: can be benign + hereditary

macrocephaly: HC > 2 SD above mean
-also can be benign+hereditary
-2/2 hydrocephalus
-or 2/2 megalencephaly - oversized brain-weight >2 SD
-Tay sachs, mucopolysaccaridoses, Canavan, Alexander’s
-also could be benign familial

hemimegalencephaly - enlarged hemisphere - hamartomatous growth - abnormal proliferation
-hemiparesis, seizures
-Tx. hemispherectomy

38
Q

Lissencephaly type 1 - LIS1, DCX

A

Miller Dieker syndrome -4 layer classic lissencephaly type 1 (smooth MILLER LIGHT (LIST) beer bottle)
-microcephaly, micrognathia, low set ears
-LIS1 gene-chromosome 17 - problem with microtubule directed migration

X linked lissencephaly - DCX gene-doublecortin in males
(DOUBLE COATING)
-if abnormal genitalia - ARX gene- + BG abnormal - type I lissencephaly

Subcortical band heterotopia - all 6 layers cortex; doublecortin (microtubules)
-DCX gene in females (lyonization- random X inactivation) - neurons with normal gene can migrate into cortex
-or mosaic mutations

39
Q

Lissencephaly type 2

A

cobblestone lissencephaly- type 2 -no cortical layers
-hydrocephalus +muscular dystrophy+eye problems (optic n atrophy, retinal hypoplasia, glaucoma, cataracts)

Cobble stone + alpha-Dystroglycanopathies
-AR; POMT1, POMT2, LARGE, FKTN

  1. muscle-eye-brain disease - eyes less affected+less cortical change vs Walker-Warburg
  2. Walker-Warburg -most severe lissencephaly inc. brainstem- brain, eye, muscle dystrophy, elevated CK, cataract, corneal opacity
  3. Fukuyama: AR , FKTN gene, fukutin mutation ; more severe muscular dystrophy— frontal white matter changes - weakness, ocular problems , CNS abnormalities, contractures , seizures, intellectual disability
    biopsy: dystrophic; reduced alpha-dystroglycan
40
Q

homocystinuria

A

cystathionine synthase deficiency (enzyme so AR)
-CBS gene on chr 21
-elevated blood, urine homocysteine + high methionine
“tall sissy homo high on meth”
-ectopia lentus (down and in vs. Marfan up and fans out), Marfanoid habitus
-intimal thickening, thromboembolism, stroke

-variants: pyridoxine response vs not responsive

Tx: B6, B12, low protein diet, low methionine diet, cystine supplementation (month of June is 6); betaine Tx alternative pathway to convert homocysteine to methionine

41
Q

colobomas

A

COACH syndrome
CHARGE syndrome (coloboma, heart defects, atresia choanae, GU, ear abnormalities)

Epidermal nevus syndrome
Patau - trisomy 13

42
Q

Heterotopia

A

Normal morphology neurons, wrong location->never migrated, remained in periventricular area

-periventricular nodular/subependymal most common
-FLNA gene-X linked - cytoskeleton stabilization - can’t attach neurons to radial glia scaffold
-affect females-X linked dominant

43
Q

Urea cycle disorders

A

Newborn presentation common except arginase deficiency

Ornithine transcarbamylase deficiency
only X-linked disorder

All others AR - carbamoylphosphate synthetase I deficiency

hyperammonemia + encephalopathy + respiratory alkalosis, no AG, normal glucose, no organic acidemia

high glutamine=edema,astrocyte swelling encephalopathy
glutamine accumulation ->astrocyte swelling, brain edema
NO organic acidemia, no anion gap

Tx: no nitrogen, no protein,
-sodium benzoat during acute episodes; mannitol for edema

44
Q

schizencephaly

A

pial to ventricle, lined with gray matter cortex

closed lip: cortex in contact
open lip: cortex separated by CSF

vs porencephaly - lined with white matter; from CSF cysts acquired in utero, not development

45
Q

polymicrogyria

A

CMV
Zellwegers peroxisome

46
Q

NF2

A

Dx: one of
-BL vestibular schwanomas
-2 of:
unilater vestibular schwannoma +/-
1st degree with NF2 +/-
2 of neurofibroma, schwanomma, meningioma, glioma, posterior subcapsular lenticular opacities
-muliple meningiomas + unilateral vestibular schwanomma or glioma/neurofibroma/schwanomma/cataract
schwannomatosis
ependymoma
meningioma

Chr 22 - merlin/schwannomin-AD

DDx -

47
Q

autism spectrum disorder

A

underdevelopment limbic system, reduced cerebellar Purkinje cells

48
Q

Down’s syndrome

A

frontal lobes small, underdeveloped
-superior temporal gyri small

-Brushfield’s spots - white spots in iris

APP-Chr 21 - amyloid precursor protein (beta-amyloid) - early dementia
Leukemia
Atalantoaxial instability

49
Q

kleinfelter

A

XXY - two X chromosome in male
-intellectual disability, gynecomastia, wide arm span

50
Q

RETT

Cri du chat

A

RETT: X linked dominant (all oblivious females can pass herRETT boys X linked disorders)
-arrest of head growth->microcephaly

MECP2 - binds methylated DNA

DDx-CDKL5
-earlier seizures - X linked

CRI-DU-CHAT - chr 5 - cat cry, micrognathia; intellectual disability

51
Q

Fragile X

A

MCC intellectual disability
-CGG repeats (child with giant gonads) on FMR1 gene (familial mental retardation 1 gene)
-RNA binding protein
-random X inactivation (lyonization) in females->less severe
-long face, protruding ears (Peter II)

52
Q

Prader Willi

Angelman’s

A

Chr 15q11p13 microdeletion

Prader Wili - paternally inherited-Maternally derived genes are silenced (imprinted)
failure to thrive as infant, hypotonia
-wide mouth, small feet, hypogonadism
-hyperphagic when older
DDx LAURENCE MOON - obesity + intellectual disability

Angelman’s - Paternally derived UBE3A gene is silenced (imprinted); Maternal allele is deleted or mutated
-microcephaly, epilepsy, ataxia, happy puppet, flailing arms

53
Q

in utero insults

A

CMV, Rubella: perventricular calcification

1st tri radiation -> intellectual disability

fetal valproate syndrome+ hydantoin (phenytoin) syndrome - intellectual disability

fetal alcohol-congenital heart disease

54
Q

Biotinidase deficiency

A

-enzyme recycles B7 + processes dietary biotin
AR inheritance, BTD gene
alopecia-TIN ROOF Smooth and shiny
-hearing, vision loss, seizures, ataxia
ketoacidosis, hyperammonemia, organic aciduria

partial deficiency-10-30% normal enzyme activity, severe <10%
Tx: free biotin supplement, can prevent disability if early
-once impaired, cannot repair deficits

55
Q

Gaucher

A

Oscar the grouch with chocolate bar on head
-glucocerebrosidase deficiency-can test in amniotic fluid
-accumulation glucocerebrosides
-GBA gene mutation Chr I

Type I - most common- HSM, anemia, pulm infiltrates; risk Parkinson’s disease otherwise no early CNS effects
Type 2 - onset before 2, most severe, die early
Type 3 - after 2 yrs, progresses slowly; oculomotor involvement - can Tx with bone marrow transplants

wrinkled tissue paper cells

Tx: enzyme replacement - imiglucerase, taliglucerase lapha, velaglucerase alpha

56
Q

Pompe

A

tx: alpha-glucosidase

57
Q

GM2 gangliosidosis

A

Tay Sachs - hexosaminidase A deficiency - HEXA gene - ONLY CNS affected
-increased startle response, motor repression, blindness
-cherry red spot, macrocephaly
-die before age 5

Sandhoff’s disease - hexosaminidase A B deficiency - HEXB gene - CNS + other organs affected ->HSM
-rare in Ashkenazi Jews

58
Q

Canavan’s disease

A

Megalencephaly
AR
—symmetric white matter disease + U fibers
deficiency aspartoacylase - >accumulate N-acetylaspartic acid (MR spec: peak N acetylaspartic acid)
-Ashkenazi Jews
-ASPA mutation chr 17
-present 2 months of life; no Tx; death in 20s

-Adrenoleukodystrophy: rim of enhancement posterior white matter - differentiate (except Alexander’s - contrast enhancement on MRI)

59
Q

Krabbe

A

globoid cell leukodystrophy
galactocerebrosidase deficiency (eyes on top of head), AR
“galacto boobs globoid” cerebro on head, nothing behind eyes = optic atrophy
-demyelination + U fibers spared
-accumulate galactocerebrosides in macrophages->globoid cells
-peripheral neuropathy

Infantile - present 4 months (maple syrup urine=at birth); regression
-hypersensitivity to stimuli->increase hypertonicity->opisthotonus, low grade fevers, optic atrophy

Juvenile - 3-10 yrs

Adult - 30s-50s

-path: PAS+ globoid macrophages - cytoplasm accumulation galactocerebroside
CSF: high protein

60
Q

Sturge Weber

A

GNAQ chr 9, sporadic

tram track calcifications -parietal, occipital -from angiomatosis
port wine stain - trigeminal distribution
-encephalotrigeminal angiomatosis - gyral calcifications from angiomatosis - leptomeninges, brain
-CNS involvements more likely is angiomas on face- esp if V1, near eye (no cataracts)
-can get enlargement of eye; hemiATROPHY of brain
-sporadic inheritance; GNAQ gene mutations

Cobb’s syndrome - cutaneomeningospinal angiomatosis - rash over spinal dural angioma

Risk: venous stasis, AVMs, venous thrombosis, capillary venous malformation

61
Q

GM1 gangliosidosis

A

lysosymal B galactosidase deficiency, AR GLB1 gene
accumulate GM1 gangliosides - brain+organs
-lipid, neuronal ballooning, atrophy

BE ONE Gangly gargoyle gal with red eyes

Like Hurler with cherry red spot + gargoyle faces
-no mucopolysacchariduria

62
Q

mucopolysaccaridoses

A

accumulate glucosaminoglycans - disaccharides-in lysosomes, extracellular matrix
-AR except Hunter

MPS Type 1-Huler -alpha-L-iduronidase deficiency (A Lazy Idaho Hurler)
dermatan+heparin sulfate elevated
-gargoyle, corneal clouding, aiway obstructuion
megalencephaly; normal at birth; develop Sx over 2 yrs
-mild form: Scheie’s syndrome
-hepatosplenomegaly

-electron microscopy - Zebra bodies
Tx: enzyme replacement (doesn’t treat CNS Sx), stem cell transplant

Hunter - iduronate-2-sulfatase deficiency (Idaho hunter with rotten SULFUR potatoes + tuber skin lesions)
-dermatan+heparin sulfate elevated
-like mild Hurler phenotype + ivory colored lesions on back+arms + aggression
-carpal tunnel; megalencephaly
-X linked

Type III-Sanfilippo - heparan sulfate only-intellectual disability, no dermatan sulfate accumulation

MPS Type IV-Morquio’s syndrome -IQ normal; short, skeletal dysplasia, corneal clouding, cardiac valve, SC compression; GLB1 mutation
-high urine glycosaminoglycan-keratan sulfate

VI-Maroteaux Lamy-normal IQ
VII-Sly’s - hydrops fetalis, intellectual disability
IX-Natowicz-deficiency hyaluroinidase, accumulate hyaluronan

63
Q

Alexander’s disease

A

GFAP mutation - AD
-infant: megalencephaly, spasticity, seizures

juvenile - childhood - bulbar Sx

adult - bulbar Sx, hyperreflexia, dysautonomia, ataxia, sleep apnea
-tadpole sign-saggital cervical spine

Rosenthal fibers - long corkscrew pink blobs - eosinophilic fibers- myeline loss-

enhancing white matter lesions -frontal lobe+anterior+U fibers involved
No Tx

64
Q

Pelizaeus-Merzbacher

A

hypomyelinating leukodystrophy - X linked recessive
-PLP1-proteolipid protein 1 mutation
-present first months of life
-nodding head, pendular nystagmus ataxia, chorea, athetosis, dystonia
-optic atrophy
-some survive to adults
-thinning corpus callosum, SPARES U fibers
-tigroid MRI (tiger spots demyelination)
peripheral myelin spared

TIGER PELT - pelizaeus, PLP1 gene

65
Q

Porphyria

A

Usually AD; during attack increased ALA + PBG

acute intermittent porphyria - PBG deaminase -AD - 6 P’s-PBG deaminase deficiency; painful abdomen, port wine urine, polyneuropathy (motor+axonal, proximal>distal; radial N involved), psych Sx, precipitated by drugs (barbituates), EtOH, starvation
-no skin lesions
-high ALA aminolevulinic acid + PBG porphobilinogenduring attack
-normal coproporphyrin

Tx: hemin, glucose-inhibits ALA synthase

variegate prophyria - protoporphyrinogen oxidase deficiency - like AIP but skin findings ; photosensitivity
-high coproporphyrin III

hepatic coproporphyria -coproporphyrinogen oxidase deficiency
-high coproporphyrin

porphyria cutanea tarda - cutaneous Sx, no CNS Sx

66
Q

Tangier

A

AR, mutation ATP-binding cassette transporter protein - ABCA1 gene, 9q31
(retro healthy tangerine has low cholesterol, high TGs; no hands or feet b/c peripheral neuropathy; TG tonsils; listening to cassettes)

-symmetric polyneuropathy-loss pain + temp feet, can mimic syringomyelia
-hand weakness, UE+LE weakness
-or multi focal mononeurpathy
-orange tonsils because TG deposited
-LOW HDL, low total cholesterol, high TG
-bone marrow biopsy: fat laden macrophages, premature atherosclerosis
Histo: foamy macrophages
Dx: clinical + lipid panel

67
Q

Menkes

A

Kinky hair syndrome, X linked, copper deficiency in liver and brain (7 MENKES MONKEYS trying to steal copper because they’re deficient - monkeys are APES - 7A)
ATP7A intracell copper transporter deficiency; no copper for enzyme cofactor
(vs Wilson’s copper accumulates-ATP7B-copper high in urine)
coarse kinky hair, light colored hair (pili torti) no eyebrows, hyperelastic skin
subdurals, hygromas, kinked intra+extra cranial vessels, full cheeks, bone fractures (may suspect abuse)

histo: cortex, thalamus, subcortex - loss of neurons, granula, Purkinje cells

-low ceruloplasmin + copper

68
Q

MELAS

A

mitochondrial encephalopathy, lactic acidosis + strokes
-mtDNA MTTL1 - encodes mtDNA tRNA
-onset 2-10 yrs
-seizures+migraines+vomiting, anorexia
stroke like episodes: altered consciousness, hemiparesis, cortical blindness
MRI - strokes not corresponding to vascular territory esp. posterior ; cause seizures

lactate: high in blood + CSF
biopsy: rapped red fibers

Tx: CoQ10, L carnitine, L arginine (acutely for stroke IV)

69
Q

Abetalipoproteinemia

A

A BETA 12 MIMIC MTTP ; no vitE bc no fat
Bassen Kornweig - AR - MTTP microsomal triglyceride transfer protein
-transports TG, cholesterol ester, PL from surfaces - no fat absorption
-demyelination of posterior columns b/c vit E defect b/c can’t absorb DEAK vitamins
-vomiting, loose stools, cerebellar ataxia
-lose proprioception hands + feet
-Labs: acanthocytosis, no LDL, no apo B, low vit E, anemia

Tx: restrict TGs, supplements DEAK

Cheng-Ching (17 decks)

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