Lysosomal Storage Disease

Question 1

Hurler’s Disease

Answer 1

Cause: a-L-Iduronidase Deficiency.
Result: Heparan sulfate and Dermatan Sulfate accumulation.
Symptoms: Mental retardation, Dwarfism, hydrocephalus, coronary artery disease, hepatosplenomegaly, coarse facial features & depressed nasal ridge, thick skin/cartilage, corneal clouding, deafness

Question 2

Hunter’s Disease

Answer 2

Cause: Idouronate sulfatase deficiency (X-linked)
Result: Accumulation of Heparan Sulfate and Dermatan Sulfate.
Sx: Less severe than Hurler’s: Progressive CNS decect and physical retardation, hepatosplenomegaly, deafness, spinal deformities, no corneal clouding like in Hurler’s.

Question 3

Tay-Sach’s Disease

Answer 3

Cause: Hexoaminidase A Deficiency
Result: Accumulation of GM2-Gangliosides in Brain tissue, skin, and retinaculoenothelial system.
Sx: mental retardation, Onion-shell inclusion due to build up of ceramides, muscle weakness & loss of motor skills, sensitive startle response, macrocephaly, dementia, blindness, MACULAR RED CHERRY SPOT.
Key word: Ashkenazi Jewish population

Question 4

Fabry’s Disease

Answer 4

Cause: a-Galactosidase Deficiency. (X-linked)
Result: Accumulation of Globosides (Galactosylceramide).
Sx: Angiokeratoma (small lesions in skin, reddish/purple), Kidney failure, muscle weakness, hypohydrosis, acroparasthesias (burning & tingling in limbs)
Tx: Recombinant enzyme therapy

Question 5

Gaucher’s Disease

Answer 5

Cause: B-glucosidase Deficiency
Result: Accumulation of Glucosylceramide, presence of “Gaucher cells”
Sx:
Type I: adult onset: hepatosplenomegaly, anaemia, bone lesions, osteonecrosis, pigmentation of hands and face.
Type II: Infantile: extensive neurodegenerative degradation, foetal oedema, hepatosplenomegaly, skin lesions, death by2 yrs old
Tx: Recombinant enzyme therapy
Keywords: Ashkenazi Jewish Population

Question 6

Neiman-Pick Disease

Answer 6

Cause: Acid sphinomyelinase Deficiency
Result: Inability to recycle sphingomyelin > accumulation of sphingomyelin, cholesterol, & glycosphingolipids > cell-death in brain, liver, spleen, lung, & bone marrow.
Sx: MACULAR-CHERRY SPOT!, presence of foamy cells.
Type A (infantile): Neurodegenerative (missense mutation, no enxyme), massive hepatosplenomegaly, spasticity, failure to thrive, unsteady gait (ataxia), discoordinate swallowing (dysphagia), slurred speech (dysarthria) > early death
Type B (adult/later in childhood): visceral chronic, non-neurodegernerative, milder, hepatosplenomegaly, degeneration of lung and liver in adults.
Dx: sphingomyelinase activity in cultured fibroblasts
Keywords: Ashkenazi Jewish Population

Question 7

I-Cell Disease

Answer 7

Cause: Phosphotransferase Deficiency
Result: inability to target lysozymes from golgi to lysosomes bc of not phosphorylating mannose
Sx: Lysozymes acumulate & leak into plasma > inclusion bodies, corneal clouding (like hurler’s), milder hepatosplenomegaly, skeletal deformities, restricted joint mov’t, severe psychomotor impairmen, severe multiple dysostosis (defective bones)
Keywords: Death btn 5-8 years

Question 8

Metachromatic Leukodystrophy (MLD)

Answer 8

Cause: Arylsulphatase A deficiency
Result: Inherited demyelinating disease (autosomal recessive), abnormal meylin tunover and accumulation of sulphatides
Sx: 3 forms:
Late Infantile: difficulty walking at 15-24 months, muslce wasting and weakness, gradual blindness, convulsions, paralysis, dementia, death by 5 yrs.
Juvenile (3-10 yrs): impaired cognitive skills > dementia, then similar to infantile path, death within 10-15 years of onset
Adult: Following puberty > progressive dementia, similar path as above but slower progress
Keywords: Symptoms at 10% or lower enzyme activity, most prevalent in Najavo nations.