Large, Sphingolipidoses Flashcards
[Met/SLs]
Examples of sphingolipidose diseases? (6)
Gaucher disease
Fabry disease
Niemann-Pick disease
Tay-Sachs disease
Krabbe’s disease
Sandhoff’s disease
[Met/SLs/Gaucher]
Major types of Gaucher disease? (3)
Type 1 Gaucher: non-CNS
Type 2 Gaucher: CNS-involved, rapidly progressive
Type 3 Gaucher: CNS-involved, slowly progressive
[Met/SLs/Gaucher]
Two other subtypes of Gaucher disease?
Perinatal-lethal Gaucher
Cardiovascular Gaucher
[Met/SLs/Gaucher]
Clinical characteristics of Type 1 Gaucher? (3)
(No CNS involvement)
Hepatosplenomegaly in presentation
Bone pains (growing pain): osteopenia, focal lytic lesions
Bone marrow infiltration: anemia, thrombocytopenia
[Met/SLs/Gaucher]
Clinical characteristics of Type 2 and 3 Gaucher? (3)
CNS involvement: limited psychomotor development
Hepatosplenomegaly
Type 2: rapidly progressive, death by 2-4 years
Type 3: slowly progressive, death by 20-30s
[Met/SLs/Gaucher]
Clinical characteristics of perinatal-leathal Gaucher? (2)
Ichthyosiform or collodion skin abnormalities
Nonimmune hydrops fetalis
[Met/SLs/Gaucher]
Clinical characteristics of cardiovascular Gaucher? (4)
Calcification of the aortic and mitral valves
Mild splenomegaly
Corneal opacities
Supranuclear ophthalmoplegia
[Met/SLs/Gaucher]
Enzyme defect, causal gene and accumulating substance in Gaucher disease?
Enzyme: Glucocerebrosidase defect
Gene: GBA
Substance: glucocerebroside
[Met/SLs/Gaucher]
Treatment for Gaucher disease type 1?
Enzyme replacement therapy (ERT): Cerezyme, VPRIV, Elelyso
Substance reducing therapy (SRT)
[Met/SLs/Gaucher]
Response to enzyme replacement therapy for type 2 and 3 Gaucher disease?
Type 2 (neurologic rapidly progressing): non-responding
Type 3 (neurologic slowly progressing): variable
[Met/SLs/Gaucher]
Population with High carrier frequency of Gaucher disease?
Ashkenazi Jewish
[Met/SLs/Gaucher]
Disease with hepatosplenomegaly and bone pain
Cells with ‘wrinkled tissue pattern’
Gaucher disease
[Met/SLs/ASMD-NPD]
Current classification of Niemann-Pick disease?
Acid Sphingomyelinase Deficiency (Niemann-Pick A and B)
Niemann-Pick type C
[Met/SLs/ASMD]
Types of Acid Sphingomyelinase Deficiency (Niemann-Pick A&B)?
Severe, early onset, Infantile neurovisceral ASMD: Niemann-Pick type A
Late-onset, Chronic visceral form ASMD: Niemann-Pick type B
[Met/SLs/ASMD]
Clinical presentation of Acid Sphingomyelinase Deficiency (Niemann-Pick A&B)? (3 by age)
For Infantile neurovisceral ASMD: Niemann-Pick type A
Hepatosplenomegaly by three months
Psychomotor deterioration and failure to thrive by 2 years
Interstitial lung disease and cherry-red spot in macula by 3 years
(Chronic visceral form ASMD: Niemann-Pick type B, similar, but slow presentation)
[Met/SLs/ASMD]
Causal gene of Acid Sphingomyelinase Deficiency (Niemann-Pick A&B)?
SMPD1
[Met/SLs/ASMD]
Treatment of of Acid Sphingomyelinase Deficiency (Niemann-Pick A&B)? (2)
Supportive
Hematopoietic stem cell transplantation (HSCT) (but doesn’t stabilize neurologic)
[Met/SLs/NPC]
[Large, SLs - NPC]
Disease mechanism of Niemann-Pick type C?
Genetic defect of NPC1 or NPC2
Involved in routing of cholesterol esters within the lysosome
[Met/SLs/NPC]
Clinical presentation of Niemann-Pick type C?
Hepatosplenomegaly, jaundice at birth
Neurologic impairment in late infancy: cataplex, narcolepsy, supra-nuclear vertical gaze palsy
[Met/SLs/NPC]
Diagnostic test of Niemann-Pick type C?
NPC1 or NPC2 gene defect
(Not an enzyme defect, Genetic defect of cholesterol ester routing protein)
[Met/SLs/NPC]
Screening test for of Niemann-Pick type C?
Assay of oxysterols
[Met/SLs/TSD]
[Large, SLs - TSD]
Three subtypes of Tay-Sachs disease?
Classic Tay-Sachs: Infantile onset
Subacute juvenile TSD: onset in toddlers
Late-onset TSD: onset in teens and young adults
[Met/SLs/TSD]
Clinical characteristics of classic Tay-Sachs disease? (5)
Onset in 3-6 months
Exaggerated startle response
Progressive weakness, loss of motor skills, seizures
Cherry red spot in retinas
Death by 4-5 years old
[Met/SLs/TSD]
Clinical characteristics of subacute/late-onset Tay-Sachs disease?
Clumsy and awkward child
Intention tremor, dysarthria, proximal muscle weakness
Psychiatric: anxiety and depression
[Met/SLs/Fabry]
Enzyme defect, gene and accumulating substance in Fabry disease?
Enzyme: Alpha-galactosidase A (α-Gal A)
Gene: GLA
Substance: Globotriaosylceramide
[Met/SLs/TSD]
Enzyme defect and accumulating substance in Tay-Sachs disease?
Enzyme: hexosaminidase A
Substance: glycolipid GM2 ganglioside
[Met/SLs/Fabry]
Clinical characteristics of classic Fabry disease? (7)
Onset: childhood or adolescence
Neuropathic pain: periodic crises of severe pain in the extremities (acroparesthesia)
Skin: angiokeratomas
Autonomic: anhidrosis, hypohidrosis, and rarely hyperhidrosis
Eye: corneal and lenticular opacities
Kidney: proteinuria, ESRD
Heme: cerebrovascular stroke, myocardial infarction
[Met/SLs/Fabry]
Clinical characteristics of late-onset male Fabry disease?
Left ventricular hypertrophy, cardiomyopathy, arrhythmia
Proteinuria; renal failure
Cerebrovascular disease
(Without skin or pain crisis)
[Met/SLs/Krabbe]
Two subtypes of Krabbe disease?
Infantile onset: <12 months
Later-onset: >12 months, varied symptoms
[Met/SLs/Krabbe]
Symptoms of infantile onset Krabbe disease? (2)
Progressive neurologic deterioration in infancy
Death before age two years
[Met/SLs/Krabbe]
Symptoms of later onset Krabbe disease? (2)
Slow development of motor milestones or loss of milestones
Seizure, spasticity, peripheral neuropathy
