November 11, 2010

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

11. Gaucher Disease

12. Gaucher Disease • Inborn error of metabolism • Affects recycling of cellular glycolipids • Defect in b-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 (b-glucocerebrosidase) • Molecular DNA analysis • Carrier testing recommended for close relatives

16. Clinical features 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

21. Storage Diseases

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

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

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