Large, Sphingolipidoses Flashcards by juhee lee

[Met/SLs]

Examples of sphingolipidose diseases? (6)

Gaucher disease
Fabry disease
Niemann-Pick disease
Tay-Sachs disease
Krabbe’s disease
Sandhoff’s disease

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[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

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[Met/SLs/Gaucher]

Two other subtypes of Gaucher disease?

Perinatal-lethal Gaucher
Cardiovascular Gaucher

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[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

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[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

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[Met/SLs/Gaucher]

Clinical characteristics of perinatal-leathal Gaucher? (2)

Ichthyosiform or collodion skin abnormalities
Nonimmune hydrops fetalis

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[Met/SLs/Gaucher]

Clinical characteristics of cardiovascular Gaucher? (4)

Calcification of the aortic and mitral valves
Mild splenomegaly
Corneal opacities
Supranuclear ophthalmoplegia

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[Met/SLs/Gaucher]

Enzyme defect, causal gene and accumulating substance in Gaucher disease?

Enzyme: Glucocerebrosidase defect
Gene: GBA
Substance: glucocerebroside

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[Met/SLs/Gaucher]

Treatment for Gaucher disease type 1?

Enzyme replacement therapy (ERT): Cerezyme, VPRIV, Elelyso
Substance reducing therapy (SRT)

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[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

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[Met/SLs/Gaucher]

Population with High carrier frequency of Gaucher disease?

Ashkenazi Jewish

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[Met/SLs/Gaucher]

Disease with hepatosplenomegaly and bone pain
Cells with ‘wrinkled tissue pattern’

Gaucher disease

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[Met/SLs/ASMD-NPD]

Current classification of Niemann-Pick disease?

Acid Sphingomyelinase Deficiency (Niemann-Pick A and B)
Niemann-Pick type C

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[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

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[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)

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[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