Lysosomal Storage Diseases Flashcards
Which lysosomal storage diseases are X-linked?
Danon, Fabry, and Hunter (Imagine a Hunter named Danon targeting an X as a Fabulous onlooker watches)
What inheritance pattern do most lysosomal storage diseases follow?
They are all autosomal recessive except for the 3 that are X-linked
Which lysosomal storage diseases occur more frequently in individuals of Ashkenazi Jewish decent?
Gaucher disease Tay-Sachs disease Niemann-Pick disease type A
Tay-Sachs Disease
Deficiency: Beta-Hexosaminidase A
Accumulated Substrate: GM2 Ganglioside
Phenotype: Cherry-red macula + blindness + rapid/progressive neurodegeneration + delayed development + seizures
Notes: NO hepatosplenomegaly + whorled configuration within lysosomes composed of ONION-SKIN layers of membranes
Side note: Sandhoff’s disease is similar but with Beta-Hexosaminidase A AND B deficiency
Nienmann-Pick Disease
Deficiency: Sphingomyelinase
Accumulated substrate: Sphingomyelin
Phenotype: Cherry-red macula + progressive neurologic deterioration + mental retardation + lung problems + hepatosplenomegaly
Notes: Foam Cells + Early Death
Fabry Disease
Deficiency: Alpha-galactosidase A
Accumulated substrate: Globotriaosylceramide (ceramide trihexoside)
Phenotype: Affects PNS (pain in hands and feet) + angiokeratomas (small dark-red spots on skin) + GI problems + hypohidrosis + tinnitus + hearing loss
Memory aid: I FABRIcated a CERAmic GALaXy
Gaucher Disease
Deficiency: Beta-glucocerebrosidase
Accumulated substrate: glucocerebroside
Phenotype: Hepatosplenomegaly + anemia + thrombocytopenia + lung disease + osteonecrosis + Erlenmayer flask distal femur deformity
Notes: Macrophages with “wrinkled paper appearance” –> Gaucher cells
Farber Disease
Deficiency: Acid ceramidase
Accumulated substrate: Ceramide
Phenotype: Hoarse voice + weak cry + lipogranulomas (lipid deposition) + swollen/painful joins with progressive joint deformities + breathing problems + hepatosplenomegaly + developmental delay
Krabbe Disease
Deficiency: Beta-Galactosylceramidase (galactocerebrosidase)
Accumulated substrate: Galactosylceramide (galactocerebroside)
Phenotype: Irritability + failure to thrive + progressive muscle weakness + unexplained fevers + stiff posture + slow mental/physical development + hearing loss + seizures
Notes: Globoid cells (large multinucleated cells)
Danon Disease
Deficiency: Lysosome-associated membrane protein 2 (LAMP-2)
Accumulated substrate: Cytoplasmic debris and glycogen
Phenotype: Cardiomyopathy + Skeletal myopathy + mental retardation
Hurler Disease (MPS I)
Deficiency: Alpha-L-Iduronidase
Accumulated substrate: Dermatan sulfate + heparan sulfate
Phenotype: Corneal clouding + dwarfism + progressive mental retardation + hepatosplenomegaly + coarse facial features + skeletal deformities (dysostosis multiplex) + large tongue
Notes: Appears normal at birth but with umbilical or inguinal hernia often present + death often by the age of 10 years d/t lung disease/infection or cardiac complications
Hunter Disease (MPS II)
Deficiency: Iduronate-2-sulphatase (I2S)
Accumulated substrate: Dermatan sulfate and heparan sulfate
Phenotype: Progressive dteterioration + enlarged tongue + hearing loss + abnormal dentition + dysostosis multiplex + clawing of hands + hepatosplenomegaly + cardiomyopathy + short stature
Notes: NO corneal clouding (a hunter needs to see) + death usually in the first or second decade of life
I-Cell disease (mucolipidosis II)
Deficiency: N-Acetylglucosamine-1-phosphotransferase
Accumulated substrate: Oligosaccharides + glycosaminoglycans (GAGs) + lipids
Phenotype: Hypotonia + developmental delay + limited mobility + clubfeet + thickened skin + short hands/fingers + possible heart valve problems + frequent respiratory infections
Notes: Present at birth or first few months of life + usually fatal before age 4
Which lysosomal storage diseases present with cherry-red macula?
Tay-Sachs and Niemann-Pick
Which lysosomal storage disease does NOT have hepatosplenomegaly?
Tay-Sachs
