Lysosomal Storage Diseases/Lipids EC Flashcards
13 y/o boy w/ episodic burning pain in hands, feet, arms, and legs after physical activity/illness. Telangiectatic non-blanching skin lesions on back. Elevated BUN/creatinine. Corneal and lenticular lesions.
Fabry disease (X-linked) Galactosidase A deficiency Ceramide trihexoside accumulation
13 y/o with increased forgetfulness. Prone to fractures. Hepatosplenomegaly and defective lateral gaze tracking. Bone marrow biopsy reveals “wrinkled tissue paper” lipid laden macrophages.
Gaucher disease (AR) Glucocerebrosidase deficiency Glucocerebroside accumulates
1 y/o w/ seizures and spastic movement. Diminished vision dyspnea, and hepatosplenomegaly. Bone marrow biopsy reveals “foam cells”. Cherry red spot on macula.
Neimann-Pick disease (AR)
Sphingomyelinase deficiency
Sphingomyelin accumulates
“NO MAN PICKS his nose with his SPHINGER”
1 y/o Ashkenazi Jewish boy brought in for lethargy. On p/e, exaggerated startle reflex, fixed gaze, large head, cherry red-spot on macula and “Onion skin” lysosomes. No hepatosplenomegaly.
Tay-Sachs disease (AR)
Hexoseaminidase A deficiency
GM2 ganglioside accumulates
“tay-saX lacks heXosaminidase”
1 y/o girl brought in for increased irritability and stiff, jerky movements. On p/e, small for age, hyperactive DTRs, hamstring rigidity. Lack of startle reflex due to decreased vision/hearing.
Krabbe’s Leukodystriphy (AR)
Galactocerebrosidase deficiency
Galactocerebroside accumulates
2 y/o boy brought in of decreased ability to stand and walk. Ataxic (& dimentia), hyperreflexive DTRs.
Metachromatic Leukodystrophy (AR) Arylsulfatase A deficiency Cerebroside sulfate accumulates
(can present as adrenal leukodystrophy w/ adrenal atrophy and Addison’s)
1 y/o boy brought to ophthalmologist due to corneal clouding. Small for age, macroglossia, coarse facial features (gargoylism), joint stiffness, valvular heart disease, corneal opacities and papilledema.
Hurler disease- Mucopolysaccharidosis (AR)
Iduronisase deficiency
Heparan sulfate/Dermatan sulfate accumulate
8 y/o boy brought in due to joint stiffness. On p/e, coarse facial features, macroglossia, small jaw, aggressive behavior, hepatosplenomegaly. Pebbly skin on back. Retinal degeneration but no corneal clouding.
Hunter’s disease- Mucopolysaccharidosis (XR)
Iduronate sulfatase deficiency
Heparan sulfate/Dermatan sulfate accumulate
“Hunters see clearly and aim for the X”
Chylomicron (function, enzyme/receptor, consequences of excess)
Transports exogenous lipids to tissues
Broken down by lipoprotein lipase
Pancreatitis, Eruptive xanthomas, Lipemia retinalis
VLDL (function, enzyme/receptor, consequences of excess)
Transports endogenous lipids from liver to tissues
Broken down by lipoprotein lipase
Pancreatitis
LDL (function, enzyme/receptor, consequences of excess)
Absorbed by tissues when cholesterol is needed
Absorbed into cells vie LDL-R
Atherosclerosis, Arcus cornea, Xanthomas
HDL (function, enzyme/receptor, consequences of excess)
Transports cholesterol to liver or steroid-hormone producing tissues
Cholesterol esterase transfer-protein binds free cholesterol in bloodstream
Apolipoprotein A (function, associated lipoprotein, diseases)
A-1 activates LCAT (traps cholesterol in HDL)
A-2-4 activate PLTP (transfer phospholipids to HDL)
Found in HDL
HDL deficiencies and hypercholesterolemia
Apolipoprotein B (function, associated lipoprotein, diseases)
B-48 chylomicrons
B-100 binds LDL-R
Found in VLDL, LDL, & chylomicrons
Deficient in abetalipoproteinemia (can’t absorb fats)
Apolipoprotein C (function, associated lipoprotein, diseases)
C-1 inhibits cholesterol ester transfer protein
C-2 activates lipoprotein lipase
C-3 inhibits lipoprotein lipase
VLDL, HDL, Chylomicrons
Increased in hypertriglyceridemia
