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90 Cards in this Set
- Front
- Back
Metachromatic Leukodystrophy
|
- AR
- Arylsulfatase A deficiency - Increased urine sulfatides |
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Tay Sach's Disease
|
- AR
- Hexosaminidase A - Ashkenazi jews and french canadians - GM-2 ganglioside accumulation |
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Niemann-Pick Disease
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- AR
- Sphingomyelinase deficiency - More common among ashkenazi jews - Foam cells on bone marrow biopsy |
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Congenital myasthenia gravis
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- Mutation in either Rapsyn (later onset)
- Mutation in AchR episilon subunit (predominantly ocular) |
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PKAN
(Neurodegeneration with brain iron accumulation type 1) Genetics |
- AR
- PANK2 gene - Chromosome 20 |
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GEFS+
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- Voltage gated sodium channel Beta-1 subunit (SCN1B or SCN1A)
- Chromosome 19 |
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NF-1
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- AD
- Chromosome 17 - neurofibromin |
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NF-2
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- AD
- Chromosome 22 - merlin |
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Friedrich's Ataxia
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- AR
- Frataxin gene on chromosome 9 - GAA repeat |
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Alzheimer's Disease genetics
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Autosomal Dominant:
- Presenilin 1 (chr 14) - most common - Presenilin 2 (chr 1) - Amyloid precursor protein on chromosome 21 - also common Sporadic: - APOe4 strongest association with late onset sporadic AD - APOe2 protective |
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Hypokalemic periodic paralysis
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- AD
- Primary defect is in a calcium channel, not potassium channel |
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Anderson-Tawill syndrome
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- AD
- Potassium channelopathy - Episodic weakness and long QT syndrome |
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Myotonia congenita
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- Chloride channel
- AD or AR - CLCN1 gene |
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Paramytonia congenita
|
- AD
- Paradoxical myotonia or induced by cold - SCN4A mutation - Sodium channelopathy |
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Huntington's Disease
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- AD
- CAG trinucleotide repeat in exonic DNA - Chromosome 4 - Need more than 39 repeats to become symptomatic - 36 to 39 are indeterminate |
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Oculopharyngeal muscular dystrophy
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- AD
- CGC repeats - PABN 1 gene - Chr 14 |
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Fragile X
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- X-linked recessive
- CGG |
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Myotonic dystrophy type 2
|
- AD
- CCTG repeat - Chr 3 |
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Spinocerebellar ataxia 12
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- CAG repeat on 5' untranslated region
|
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Tuberous Sclerosis (genetics)
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- AD
- TSC1 (Hamartin) on Chr 9 - TSC2 (Tuberin) on Chr 16 |
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Rett's disease
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- X chromosome
- MECP-2 - Mutation is fatal in boys |
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Familial parkinsonism
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- Alpha synuclein
- Chromosome 4 |
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Charcot-Marie-Tooth Type 1A
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- Duplications in peripheral myelin protein 22 (PMP22)
- AD |
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Charcot-Marie-Tooth Type 1B
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- Myelin Protein zero (MPZ)
- AD |
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Hereditary neuropathy and liability to pressure palsies
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- Deletions in PMP22
- AD - Chr 17 |
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McArdle's disease
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- Type V glycogen storage disease
- Enzyme is myophosphorylase - Causes glycogen accumulation |
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Holoprosencephaly
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- Sonic hedgehog
- Trisomy 13 - Associated with cyclopea, ethmocephaly (proboscis) - Developmental delays, seizures, swallowing difficulties |
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Zellweger's syndrome
|
- AR
- PEX 3 - Peroxysomal storage disorder (increased VLCFA) - Liver, kidneys, brain - hepatomegaly, renal failure, hypotonia, elevated serum iron and copper, vision disturbance - Abn gyral patterns, impaired myelination, periventricular pseudocysts |
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X-linked lissencephaly
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Doublecortin
- In males, this gene causes lissencephaly - In females in causes cortical band heterotopia |
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Heterotopias
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- laminin (band like)
- filamin (nodular) |
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Hartnup's disease
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- AR
- Metabolic disorder of absorption of neutral amino acids - These are typically converted to serotonin, melatonin, niacin - Need niacin repletion |
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CACH (childhood ataxia with central hypomyelination)
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- AR
- Mutation in eukaryotic initiation factor (eIF) 2B - A leukodystrophy - Present before age 6, rapid progression - On path, cystic WM degeneration |
|
Fabry's disease
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- X-linked lysosomal storage disorder
- Decreased alpha galactosidase A activity - Lipid laden macrophages in bone marrow - Enzyme replacement available |
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Sandhoff's disease
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- Hexosaminidase B deficiency
|
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Canavan's disease, genetics
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- AR, more common in jewish descent
- Aspartoacylase deficiency - High NAA |
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Pompe's Disease
|
- Alpha 1,4 glucosidase deficiency (also called acid maltase)
- A glycogen storage disorder (lysosomal) - Enlarged tongue, hypotonia, cardiomegaly with shortened PR interval - Replace enzyme or death within first year of life |
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Glycogen storage diseases
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0 - glycogen synthase deficiency
Ia - von Gierke's disease (glucose-6-phosphotase) II - Pompe's disease (acid maltase or alpha 1,4 glucosidase) III - Forbes-Cori disease (debranching enzyme) IV - Anderson's disease, amylopectinosis (Translucosidase) V - McArdle's disease (myophosphorylase) VI - Hers disease (Phosphorylase) VII - Tauri disease (phosphofructokinase deficiency) |
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Refsum's disease (genetics)
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- AR, peroxisomal disorder
- phytanic acid oxidase (phytanoyl coA hydroxylase) mutation |
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Episodic ataxia I
|
- AD
- K+ channel - Attack minutes to hours - EMG shows myokymia - Normal MRI - Associated with epilepsy - Attacks improve with age - Treat with acetazolamide |
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Episodic ataxia II
|
- AD
- Ca2+ channel - Attacks last hours to days - No EMG findings - MRI shows cerebellar atrophy - Associated with migraine - Progressive course of disease - Treat with acetazolamide |
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PKU
|
- AR
- Defect in phenylalanine hydroxylation to tyrosine in liver - Mousy urine odor - Restrict phenylalanine |
|
Homocystinuria
|
- AR
- deficiency in cystathione B-synthase - Accumulation of homocysteine in serum and urine - Enhanced reconversion to methionine - Marfanoid habitus - Mental retardation - Thromboses - Treat with folate and pyridoxine |
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Maple Syrup urine disease
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- AR
- branched chain ketoaciduria - deficiency in decarboxylase that initiates degradation of leucine/valine - Can cause seizures, lethargy, opisthotonus - 10-14 days |
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Organic acidurias
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- Methylmalonic acidemia, propionic acidemia, isovaleric acidemia
- Acidosis, hyperammonemia, hyperglycemia - treatment to stop catabolism: give glucose, not protein - Supplement with carnitine - At risk for basal ganglia infarction during acute metabolic decompensation |
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Urea cycle defects
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- X-linked recessive
- most common is OTC deficiency - Hyperammonemia and orotic acid in urine - Treat with protein restriction |
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Nonketotic hyperglycinemia
|
- AR
- neonatal CNS deterioration, seizures, respiratory depression - Test simultaneous glycine in plasma and CSF |
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Biotinidase deficiency
|
- AR
- Seizures prominent, hypotonia, alopecia, skin rash, acidosis, immunodeficiency - Supplement with biotin |
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Glutaric aciduria I
|
- Macrocephaly, dystonia, acidosis, idiopathic subdurals may occur
- Treat with low protein diet, riboflavin, depakote, baclofen (increase GABA) |
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Glutaric aciduria II
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- Electron transport chain defect
- AR |
|
Adrenoleukodystrophy
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- X-linked
- Defect of B-oxidation, accumulation of VLCFA - Childhood most common, 4-8 years - Learning disabilities, cognitive and behavioral problems, blindness, quadriparesis, seizures in 20% - Adrenal insufficiency, hyperpigmented skin - VLCFA are increased - Demyelination on MRI (posterior) with peripheral enhancement - no good treatment (bone marrow transplant) |
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Adrenomyeloneuropathy
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- Presents in adult males between 20-40
- Spinal cord dysfunction with progressive stiffness and weakness of legs. May present as progressive cerebellar disorder |
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Lysosomal storage disorders (mucopolysaccharidoses) type I
|
I - Hurler's (iduronidase), corneal clouding, MR, dysostosis multiplex, bone marrow transplant
|
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MPS
|
II - Hunter's (X linked recessive), iduronate 2 sulfatase, no corneal opacities, profound MR
Others not likely to show on exam? |
|
Lysosomal storage disorders
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Type I Gaucher's disease
Type A Niemann-Pick type B Niemann-Pick Type C Niemann-Pick Tay -Sachs Metachromatic leukodystrophy Fabry's disease Krabbe's disease |
|
Krabbe's disease
|
- B-galatosidase deficiency
- Four forms, infantile, late infantile, juvenile, and adult - FTT, optic atrophy, blindness, hyperiritability, CNS degeneration, seizures, decerebrate posturing late - Diffuse atrophy on MRI, decrease NC velocity, increase CSF protein |
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Menke's disease
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- X-linked disorder of copper transport
- CTP7A -> copper deficiency - 2-3 months of age - hypotonia, seizures, FTT, changes in hair, autonomic dysfunction - Death by age 3, but can inject copper before 10 days of age |
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Alexander's disease
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- AD but most are de novo mutations
- Infantile most common but also juvenile and adult - Birth to early childhood, with regression, macrocephaly, spasticity, seizure - Death by age 2 - Progressive leukodystrophy affecting deep white matter, spares periventricular region, frontal predominance - Mutation in GFAP |
|
Vanishing white matter disease
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- Leukodystrophy
- AR, variable age of onset - Head trauma or infection followed by rapid deterioration - Cerebellar ataxia, spasticity, seizures - MRI showed WM disease and cystic degenerative changes. Spares the temporal lobes - eIF2B |
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Pelizaeus-Merzbacher disease, genetics
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- X-linked
- PLP gene (Xq22) - The same gene causes C-linked spastic paraplegia |
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CCM (cerebral cavernous malformations)
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- KRIT-1 in hispanics
|
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Melas
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- Mitochondrial
- tRNA leucine |
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Atypical teratoid/rhabdoid tumors
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- Chromosome 22
- INI1 gene |
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Neuroacanthocytosis
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- Chromosome 9
- AR - abnormality in membrane lipids - orofacial dystonia, chorea, tics, motor neuropathy |
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PARK 1,4
|
- AD
- Chromosome 4 - alpha synuclein - Usually de novo |
|
PARK 3
|
- AD
- Chromosome 2 - Unknown function |
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PARK 5
|
- AD
- Chromosome 4 - Ubiquitin C-terminal hydrolase L1 |
|
PARK 2
|
- AR
- Chromosome 6 - Parkin (E3 ubiquitin ligase with alpha synuclein as a substrate) - Onset 20-40 years of age |
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PARK 6
|
- AR
- Chromosome 1 - PINK-1 |
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PARK 7
|
- AR
- Chromosome 1 - DJ-1 |
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PARK8
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- LRRK2 (codes for dardarin protein)
|
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Early onset dystonia
|
- AD
- Torsin A - GAG deletion - Childhood onset |
|
Segawa syndrome (dopa responsive dystonia)
|
- AR
- Tyrosine hydroxylase mutation |
|
DOPA responsive dystonia-parkinsonism
|
- AD
- GTP cyclohydrolase (synthesizes cofactor for DA synthesis) |
|
Myoclonic dystonia
|
- AD
- E Sarcoglycan gene. (note sarcoglycans also mutated in AR limb girdle musculodystrophy) |
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PSP
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- 90% homozygous for H1 allele of tau gene but 60% of normal population is too.
|
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H1 haplotype
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- PSP, CBGD
|
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H2 haplotype
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- FTD
|
|
FTD familial
|
- Chromosome 17 (tau gene)
|
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HSP
|
- SPG genes, multiple chromosomes
- Spastin, atlastin, seipin, paraplegin, L1CAM, PLP |
|
SCA-1, 2, and 3, also 7
|
- AD
- CAG trinucleotide repeat in ataxin 1, 2, or 3, 7 (ataxin degrades ubiquitin) - 3 is machado joseph (German or Portuguese) |
|
SCA-6
|
- CACNA1A (p/q type ca channel)
- This gene also causes episodic ataxia type 2 and familial hemiplegic migraine - Onset greater than 50 years of age |
|
SCA-10
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- Pentanucleotide repeat
- Seizures - Mexicans |
|
Ataxia-telangectasia
|
- ATM gene (Tumor suppressor)
- 7->14 chromosomal translocation - Reduced Ig except IgM, increased alpha fetoprotein - Cerebellum atrophic |
|
Myotonic distrophy Type I
|
- AD
- CTG repeat - Chr 19 |
|
Fascio-scapular-humeral muscular dystrophy
|
- AD
- Chr 4 |
|
Duchenne's and Becker's genetics
|
- X-linked recessive
- Dystrophin |
|
Emery Dreifuss MD (genetics)
|
- X linked recessive
- Emerin (nuclear membrane prot) - Lamin A/C in type 2 (note also in LGMD type 1 and CMT 2a |
|
LGMD type 1
|
- AD
- Lamin A/C (note also mutated in CMT 2a, E-D type 2), caveolin-3, myotilin |
|
LGMD tyle 2
|
- AR
- Calpain 3, dysferlin, sarcoglycans |
|
Williams syndrome
|
- Chromosome 7 deletion
- Happy, trusting children |