Diseases! Flashcards
1
Q
Ashkenazi Jewish descent lysosomal storage diseases
A
GTP:
Gaucher disease
Tay-Sachs disease
Niemann-Pick disease type A
autosomal recessive
2
Q
X-linked lysosomal storage diseases
A
Danon, you are a Fabulous Hunter! (X)
Danon (X-linked dominant)
Fabry
Hunter’s
3
Q
Tay-Sachs disease
A
- autosomal recessive
- beta-hexosaminidase A deficiency –> accumulation of GM2 ganglioside –> progressive neurodegeneration
- cherry-red macula, blindness, delayed development, seizures
- no hepatosplenomegaly
- whorled configurations within lysosomes (onion-skin layers of membranes)
4
Q
Sandhoff’s disease
A
- similar to Tay-Sachs disease, also due to deficiency in beta-hexosaminidase A/B –> accumulated GM2 ganglioside
- YES hepatosplenomegaly
5
Q
Niemann-Pick disease
A
- autosomal recessive
- deficincy in sphingomyelinase –> sphingomyelin accumulation in cell membrane
- progressive neurologic deterioration, cherry-red macula, lungs affected, hepatosplenomegaly
- foam cells
6
Q
Gaucher disease
A
- autosomal recessive
- deficiency in beta-glucocerebrosidase –> accumulation of glucocerebroside
- Erlenmayer flask distal femur, hepatosplenomegaly, blood abnormalities (anemia, thrombocytopenia), lung disease
- macrophages with wrinkled paper appearance
7
Q
Fabry disease
A
- X-linked recessive
- deficiency in alpha-galactosidase A –> accumulation of globotriaosylceramide (aka ceramide trihexoside, a glycolipid)
- angiokeratomas (small red dots), hypohidrosis, dysesthesia (pinprick pain), neuropathy, GI problems, hearing problems
8
Q
Danon disease
A
- X-linked dominant
- deficiency in lysosome-associated membrane protein 2 (LAMP-2) –> accumulation of cytoplasmic debris and glycogen
- cardiomyopathy, skeletal myopathy, mental retardation
9
Q
Hunter disease
Mucopolysaccharidosis (MPS) Type II
A
- X-linked recessive
- deficiency in iduronate-2-sulphatase (I2S) –> accumulation of dermatan sulfate, heparan sulfate
- progressive deterioration, coarse facial features, enlarged tongue, hearing loss, abnormal dentition, skeletal deformities, clawed hands, hepatosplenomegaly, cardiomyopathy, severe short stature
- NO corneal clouding
10
Q
Hurler disease
Mucopolysaccharidosis (MPS) Type I
A
- autosomal recessive
- deficiency in alpha-L-iduronidase –> accumulation of dermatan sulfate, heparan sulfate
- umbilical/inguinal hernas often present at birth
- progressive deterioration, dwarfism, hepatosplenomegaly, coarse facial features, skeletal deformities, large tonge
- YES corneal clouding
11
Q
Farber disease
Farber lipogranulomatosis
A
- autosomal recessive
- deficiency in acid ceramidase –> accumulation of ceramide
- hoarse voice/weak cry, lipogranulomas (small lumps of fat under skin), swollen and painful joints with progressive joint deformities
- breathing problems, hepatosplenomegaly, developmental delay
12
Q
Krabbe disease
globoid cell leukodystrophy
A
- autosomal recessive
- deficiency in beta-galactosylceramidase –> accumulation of galactosylceramide (galactocerebroside)
- irritability, failure to thrive, progressive muscle weakness, slowed mental/physical development, hearing loss, vision loss, seizures
- abnormal presence of globoid cells
13
Q
Metachromatic Leukodystrophy
A
- autosomal recessive
- Cerebroside sulfate accumulation in neural and non-neural tissue → progressive demyelination of the central and peripheral nervous system
- Motor regression and developmental delay, ataxia, optic nerve atrophy → loss of vision, flaccid paralysis followed by spastic paralysis
14
Q
I-Cell disease
mucolipidosis II
A
- autosomal recessive
- deficiency in N-acetylglucosamine-1-phosphotransferase –> accumulation of oligosaccharides, glycosaminoglycans, lipids (mannose phosphate)
- hypotonia, developmental delay, limited mobility, clubfeet, thickened skin, short hands/fingers, gingival hypertrophy
- heart valve abnormailities, repeated respiratory infections
15
Q
Patau syndrome
A
- trisomy 13
- low birth weight, cleft lip/palate, hypotelorism (decreased distance between eyes), CNS anomaly, polydactyly, rocker bottom feet
16
Q
Edwards syndrome
A
- triosmy 18
- low birth weight, prominent occiput, tightly clenched fists with overlapping fingers, clubfoot, rocker bottom feet, heart defects, CNS abnormalities
17
Q
Down syndrome
A
- trisomy 21
- hypotonia, characteristic facial features, developmental delay, heart/GI defects
18
Q
Turner syndrome
A
- monosomy X (45, X)
- short stature, amenorrhea, lack of secondary sexual development, infertility, learning disabilities
19
Q
Klinefelter syndrome
A
- 47,XXY
- small testes, infertility, gynecomastia (overdevelopment of breast tissue in males), tall stature, hearing problems, learning disabilities
20
Q
DiGeorge syndome
A
- 22q11.2 microdeletion
- craniofacial anomalies, intellectual disability, immunodeficiency, heart defects, absence of parathyroids/thymus
21
Q
Williams syndrome
A
- 7q11.23 deletion
- low birth weight, mild-moderate intellectual disability, distinctive facial features, cardiovascular problems, friendly outgoing personality
22
Q
Cri du chat syndrome
A
- microdeletion of the short arm at chromosome 5 (46,XX,5p- or 46,XY, 5p‑)
- Cat-like high-pitched crying in affected infants, congenital heart defects (e.g., VSD) microcephaly, intellectual disability (moderate to severe), single palmar crease, dysmorphic facial features
23
Q
Prader-Willi syndrome
A
- 15q11.2-q13 deletion on paternal chromosome OR maternal uniparental disomy
- neonatal hypotonia, obesity, excessive eating habits, small hands/feet, short stature, hypogonadism, intellectual disability
Prader misses his papa
24
Q
Angelman syndrome
A
- 15q11.2-q13 deletion on maternal chromosome OR paternal uniparental disomy OR UBE3A gene mutations
- distinct facial appearance, short stature, severe intellectual disability, spasticity, seizures
Angel misses her mama
25
Q
Fragile X syndrome
A
- CGG repeat expansion in 5’UTR of FMR1 gene
- X-linked dominant
- moderate intellectual disability, long narrow face with large ears, macrocephaly, macroorchidism (abnormally large testes), flexible joints
Fragile X has X-tra large ears, testes, dominant
fragile, CGG repeat
26
Q
Friedreich ataxia
A
- GAA repeat expansion in intron of FXN gene
- autosomal recessive
- unsteady movements, impaired sensory functions, hesitant/slurred speech, heart disease, diabetes
ataxia, GAA repeat
27
Q
Huntington disease
A
- CAG repeat expansion in exon of HD(HTT) gene
- autosomal dominant with paternal transmission bias
- motor abnormalities, personality changes, gradual loss of cognition
Hunting cags
28
Q
myotonic dystrophy 1
A
- CTG repeat expansion in 3’UTR of DMPK gene
- autosomal dominant
- muscle wasting/weakness, myotonia, facial features, cardiac conduction defects, hormonal changes, cataracts
29
Q
Rett syndrome
A
- mutations in MECP2 gene
- X-linked dominant
- language/communication problems, brain function problems, loss of purposeful hand use (hand wringing, washing, clapping), slow growth, microcephaly
Rett, hand wringing
30
Q
Ehler-Danlos syndrome
A
- pathogenic mutations in at least 20 genes
- most common: classical form caused by variants of COL5A1 or COL5A2 genes
- classical form is autosomal dominant
- hypermobility, hypotonia, highly elastic and fragile skin, easy bruising, unusual scarring, pseudotumors, ocular defects
31
Q
Marfan syndrome
A
- mutations in FBN1 (fibrillin) gene
- autosomal dominant
- tall and slender, elongated fingers/toes, loose joints, vision problems, risk of aortic aneurysm
