Treatable Genetic DisordersRoad to the CureHannah ObasiGenomics & MedicineDoug Brutlag3.10.11Treatable Genetic Disorders:Treatment v. CureChronic Myelogenous LeukemiaAcute Promyelocytic LeukemiaBiotinidase DeficiencyPompe DiseaseTreatable Genetic Disorders:Chronic Myelogenous LeukemiaAcute Promyelocytic LeukemiaBiotinidase DeficiencyPompe DiseaseTreatable Genetic Disorders:Chronic Myelogenous LeukemiaTreatable Genetic Disorders:•Cancer of blood cells•Proliferation disorder of pluripotent stem cell•Myeloid, erythroid, megakaryocytic, B lymphoid, etc.•Possibly enlarged spleen and liverWhat is it?Treatable Genetic Disorders:Chronic Myelogenous LeukemiaWhat causes the overproliferation?“Philadelphia” chromosome•Translocation event (between 9 & 22)•Fuses BCR and ABL gene–Activates tyrosine kinase activityTreatable Genetic Disorders:Chronic Myelogenous LeukemiaWhat causes the overproliferation?•Translocation event (between 9 & 22)•Fuses BCR and ABL gene–Activates tyrosine kinase activityTreatable Genetic Disorders:Chronic Myelogenous LeukemiaWhat causes the overproliferation?Chronic Myelogenous LeukemiaTreatable Genetic Disorders:DiagnosisTreatment•Complete blood count•Detecting the Philadelphia chromosome•PCR for the BCR-ABL gene•Imatinib (STI571)•Brand name: Gleevec•Deactivates BCR-ABL proteinChronic Myelogenous LeukemiaAcute Promyelocytic LeukemiaBiotinidase DeficiencyPompe DiseaseTreatable Genetic Disorders:Acute Promyelocytic LeukemiaTreatable Genetic Disorders:What is it?•Similar to CML•Cancer of the blood; bone marrow •Deficiency of mature cells in myeloid line•Excess immature cells (promyelocytes)Symptoms•Fatigue•Minor infections•Hemorrhagic diathesis•AnemiaAcute Promyelocytic LeukemiaTreatable Genetic Disorders:What causes the overproliferation?Acute Promyelocytic LeukemiaTreatable Genetic Disorders:What causes the overproliferation?•Translocation event (between 15 and 17)•PML/RARa fusion gene•PML: growth suppressor transcription factor•RARa: retinoic acid receptor alpha •Regulates myeloid differentiationAcute Promyelocytic LeukemiaTreatable Genetic Disorders:DiagnosisTreatment•Complete blood cell count•Chromosome phenotype•Test for PML/RARa geneAcute Promyelocytic LeukemiaTreatable Genetic Disorders:Treatment•ATRA: all-trans retinoic acid•Malignant cells phenotypically mature myeloid cellsChronic Myelogenous LeukemiaAcute Promyelocytic LeukemiaBiotinidase DeficiencyPompe DiseaseTreatable Genetic Disorders:Biotinidase DeficiencyTreatable Genetic Disorders:What is it?•Autosomal recessive•Absence of biotinidaseFunction of biotinidaseBiotinidase DeficiencyTreatable Genetic Disorders:What is it?•Autosomal recessive•Absence of biotinidaseFunction of biotinidaseDeficiency symptoms•infantile or early childhood encephalopathy, •seizure disorder•dermatitis •alopecia•neural deafness •optic atrophy•Biotin cycling•Carboxylase enzyme co-activationBiotinidase DeficiencyWhat causes the deficiency?Treatable Genetic Disorders:•BTD gene mutationBiotinidase DeficiencyDiagnosisTreatable Genetic Disorders:•Measure biotinidase enzyme activity•Test BTD geneTreatment•Biotin therapy•Children: 5 – 10 mg/dayChronic Myelogenous LeukemiaAcute Promyelocytic LeukemiaBiotinidase DeficiencyPompe DiseaseTreatable Genetic Disorders:Pompe DiseaseTreatable Genetic Disorders:What is it?•Glycogen storage disease type II•Acid maltase deficiency•Buildup of glycogen in cells•Impairs cell function•Autosomal recessiveSymptoms•Classic infantile-onset•Muscle weakness•Cardiomegaly•Feeding difficulties •Respiratory distress•Hearing loss•Non-classic infantile-onset•Motor delays•Ventilatory failure deathPompe DiseaseWhat causes the disease?Treatable Genetic Disorders:•Mutation in GAA genePompe DiseaseTreatable Genetic Disorders:Diagnosis Treatment•Measure alpha-glucosidase (GAA) enzyme activity•Test GAA gene•enzyme replacement therapy (ERT) with Myozyme® or Lumizyme®Treatable Genetic Disorders:Treatment v. Curelast note•Gene Therapy•Stem Cell ResearchReferences
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