1. November 11, 2010

8. Undernutrition

10. 61/2 m/o ex 34 WGA twins with: FTT Severe Global Developmental Delay Hypertonia Oculomotor findings Reflux Intermittent Diarrhea HSM h/o neutropenia and thrombocytopenia

12. Gaucher Disease Inborn error of metabolism Affects recycling of cellular glycolipids Defect in  -glucocerebrosidase Accumulation of glucocerebroside in lysosomes Most common lysosomal storage disease Incidence 1/75,000 worldwide Autosomal recessive

13. Clinical Presentation Neurologic dysfunction Developmental Delay Oculomotor dysfunction Pathologic fractures Hepatosplenomegaly Anemia Neutropenia Thrombocytopenia Cardiac and renal symptoms typically absent

14. Gaucher Disease Ashkenazi Jews 7% heterozygous Frequency of disease 1:1000 Also common among Swedish

15. Diagnosis Gaucher cells in bone marrow False negatives Gold Standard: Enzyme assay (  -glucocerebrosidase) Molecular DNA analysis Carrier testing recommended for close relatives

16. Three Clinical Types

17. Type 1 Adult onset Most common Most closely tied with Ashkenazi Jews NO CNS findings Varies from mild to severe Enzyme replacement: near-normal life expectancy

18. Type 2 Most severe form Death by age 2 Treatment usually not indicated Early, severe CNS involvement Brainstem abnormalities

19. Type 3 Juvenile onset “chronic/subacute form” Most common in Swedish Later onset: Incoordination, mental deterioration, seizures Slowly progressive Becomes severe in later childhood

20. Treatment Enzyme replacement therapy Glucocerebrosidase IV Some improvement within 6 months Not effective for CNS symptoms Research Oral therapy Gene therapy

22. Lysosomal Storage Diseases Mutation in gene coding for production of lysosomal enzymes Accumulation of substrate Impairment of cell function >40 different LSD Start in late infancy or early childhood with slowly progressive symptoms

23. Lysosomal Storage Diseases Mucopolysaccharides Hurler’s Hunter’s Sanfilippo Morquio Glycolipids Gaucher Fabry Krabbe Tay Sachs

24. Lysosomal Storage Diseases Mucopolysaccharidoses Cannot break down glycosaminoglycans Clinical effects Coarsening of facial features Skeletal abnormailities Dysostosis multiplex Joint structure and function Organomegaly +/- Cognitive abilities +/- Corneal clouding Treatment: enzyme replacement or BMT

25. DiseaseDescriptionInheritance Hurler’s (MPS I)+ corneal clouding + developmental regression AR Hunter’s (MPS II)no corneal clouding + developmental regression X-linked Sanfilippo (MPS III)no corneal clouding + developmental regression AR Morquiro (MPS IV)+ corneal clouding * Normal intelligence AR

26. Lysosomal Storage Diseases Sphingolipidoses Developmental regression Organomegaly Cherry red macula Bone pain Short

27. DiseaseDescription GaucherHSM, bone pain, easy bruisibility FabryOrange-colored skin lesions, opacities of the eye, vascular disease (heart, brain, kidney) KrabbeDemyelination and progressive neuro deterioration Tay SachsNo HSM, cherry red spot, neuro deterioration Niemann-PickHSM, cherry red spot, peripheral neuropathy

28. Glycogen Storage Disease Von Gierke Disease (GSD I) Liver can’t produce glucose Features Hypoglycemia with prolonged fasting Organomegaly Cherubic face Poor growth Elevated TG and cholesterol Lab findings Elevated lactic and uric acid Treatment Frequent snacks and meals

29. Glycogen Storage Disease Pompe Disease (GSD II) Cannot use muscle glycogen Features Muscle weakness Muscles are hard Rhabdomyolysis FTT Macroglossia Cardiomegaly Treatment Enzyme replacement