LYSOSOMAL STORAGE DISORDERS

Question 1

GAUCHER DISEASE

Answer 1

Three types: Type 1&raquo_space; Non-neuropathic (no CNS involvement); Bone disease; hepatosplenomegaly, thrombocytopenia > anemia, lung disease; Type 2, 3&raquo_space; Neuropathic; Type 1 features + neurologic degeneration and cognitive impairment; Ashkenazi Jewish (1/15 carrier frequency) 4 founder mutations; Increased risk for Parkinson’s disease; Genetics: GBA gene; A recessive; Testing: Carriers»enzyme testing not reliable; Diagnosis: 1. Enzyme assay 0-15% activity 2. GBA sequencing or targeted for AJ founder mutations; Treatments may include ERT, substrate reduction (Gaucher caused by accumulation of glucocerbrosides) therapy, bone marrow transplant

Question 2

FABRY DISEASE

Answer 2

Periodic crises of sever pain in extremeties (acroparathesis), angiokeratomas, sweating abnormalities, corneal and lenticular opacities; cardiac hypertrophy, renal insufficiencies, Genetics: GLA gene ; *X-linked, Diagnosis: 1. enzyme assay for alpha-GAL-A in males (<1% activity = classic Fabry) 2. GLA sequencing

Question 3

NIEMANN-PICK DISEASE

Answer 3

Mutliple typesHepatosplenomegaly, lung disease, eye abnormality cherry-red spot (Type A); Genetics: Type A and B = SMPD1 gene (mutations cause lipid accumulation in cells); Type C = NPC1 or NPC2; A recessive; Type A&raquo_space; AJ founder mutations

Question 4

TAY-SACHS DISEASE

Answer 4

Three forms (infantile, juventile adult); Progressive neurodegeneration to vegetative state, *cherry red spot on eye exam, *increased startle response; Genetics: 
 Enzyme:  hexaminidase A, Gene: HEXA, A recessive; Testing Strategy:  enzyme assay recommended for non-AJ/FC/C, common mutation panel for carrier screening appropriate, combined enzyme and DNA testing yields highest sensitivity; **enzyme assay should be done on leukocytes for pregnancy women or those on birth control; Ashkenazi Jewish ancestry (1/31 carrier frequency)

Question 5

MPS 1 (AKA HURLER)

Answer 5

Skeletal abnormalities; coarse facial features, short stature, corneal clouding; *gibbus of lower spine and DD); Genetics: IDUA gene, A recessive; Testing: Elevated urine GAGs

Question 6

MPS II (AKA HUNTER)

Answer 6

Skeletal abnormalities; coarse facial features, short stature, *NO corneal clouding; Genetics: IDS gene; **X-linked; Testing: Elevated urine GAGs

Question 7

MPS III (AKA SANFILIPPO)

Answer 7

Skeletal abnormalities; coarse facial features, corneal clouding; **NML stature, severe neuro pheno, sleep disturbance; Genetics: A recessive; Testing: Elevated urine GAGs

Question 8

MPS IV (AKA MORQUIO)

Answer 8

Skeletal abnormalities; coarse facial features, short stature, corneal clouding, *nml IQ; Genetics: GALNS, GLB1, A recessive

Question 9

MPS VI (AKA MAROTEAUX-LAMY)

Answer 9

Skeletal abnormalities; coarse facial features, short stature, corneal clouding, *nml IQ; Genetics: ARSB gene, A recessive

Question 10

POMPE DISEASE (AKA GSD III)

Answer 10

Infantile and Late onset forms»Infantile form includes HCM + hypotonia, generalized muscle weakness, respiratory distress; Late onset includes proximal muscle weakness and respiratory insufficiency **w/o HCM