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102 Cards in this Set
- Front
- Back
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what are the lysosomal storage diseases?
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Tay-Sachs and Gaucher Diseases
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what are the glycogen storage diseases?
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Von Gierke’s and Pompe’s Diseases
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how can you classify genetic disorders?
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Mendelian Single Gene Disorders
- Autosomal Dominant - Autosomal Recessive - X-linked Non-Mendelian Single Gene Disorders Multi factorial Disorders Chromosomal Disorders |
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what are exs of autosomal dominant disorders?
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Neurologic: Huntington’s Disease
Renal: Polycystic Kidney Disease GI: Familial Polyposis Coli Heme: Hereditary Spherocytosis Skeletal: Marfan Syndrome Metabolic: Familial Hypercholesterolemia |
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what are exs of X linked disorders?
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Musculoskeletal: Muscular Dystrophy
Heme: Hemophilia Metabolic: Lesch-Nyhan Syndrome Neurologic: Fragile X Syndrome |
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what genetic disorders result from of messed up/missing enzymes that metabolize a.a.?
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Phenylketonuria
Maple Syrup Urine Disease Homocystinuria |
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what genetic disorders result from of messed up/missing enzymes?
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Galactosemia
Congenital Adrenal Hyperplasia MCAD (Fatty Acid Oxidation) Lysosomal Storage Diseases Glycogen Storage Diseases |
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what genetic disorders result from messed up/missing enzyme inhibitors?
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Alpha-1-Antitrypsin Disorder
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what genetic disorders result from messed up/missing transport molecules?
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Sickle Cell Anemia
Cystic Fibrosis Hemochromatosis |
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how do you screen the population for gene disorders?
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newborns
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when do you test family or at-risk testing?
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Prenatal
Carrier Detection |
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how do you test to find out if genetic disorder?
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Clinical Findings
Measure Abnormal Accumulations Measure Enzyme Activity or Phenotype Morphologic Changes in Tissues Gene Defect or Mutation |
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what are newborns tested for?
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Pathology - Newborn Screening Laboratory: (population based testing -all newborns)
Phenylketonuria Homocystinuria Maple Syrup Urine Disease Galactosemia Hypothyroidism Sickle Cell Anemia Congenital Adrenal Hyperplasia Biotinidase Deficiency Other Disorders (detectable by MS/MS techniques) Fatty Acid Metabolism defects Organic Acid Metabolism defects Other Amino Acid Metabolism defects Pediatrics Programs/Services: (selected testing) Others: Genetics, Pathology, Neurology, etc: (selected testing) |
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how do you collect sample from baby for testing?
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put drops of blood on filter paper
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what's the incidence of phenylketonuria?
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Incidence: 1:12,000
Classical - 1:20,000 Hyper-phenylalaninemia - 1:20,000 |
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how is phenylketonuria transmitted?
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auto recess
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what's the problem in phenylketonuria?
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Phenylalanine Hydroxylase (decrease activity)
Accumulations of Phenylalanine and metabolites *toxic to neural tissue |
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what are the symptoms of phenylketonuria?
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Mental Retardation
Motor Dysfunction Seizures |
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how do you diagnosis phenylketonuria?
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Phenylalanine (blood)
Tyrosine (blood) |
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what's the phenylalanine metabolic pathway?
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tx phenylketonuria?
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limit phenylalanine in diet
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what newborn test is used for pku?
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guthrie testing: bac inhibition assay
BIA plate (guthrie test) - elevated phenylalanine: old method current: ms/ms |
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what's the incidence of maple syrup urine disease (MSUD)?
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1: 250,000
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what's the inheritance of MSUD?
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auto recess
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what's the defect in MSUD?
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Branch Chain keto-acid decarboxylase
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what's the pathology/symp in MSUD?
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Acidosis
retardation respiratory failure |
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how do you diagnose MSUD?
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Leucine/Isoleucine (screen), Valine levels
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what's the incidence of homocystinuria (HCU)?
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1:60,000-150,000
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what's the inheritance of HCU?
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auto recess
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what's the defect in HCU?
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Cystathionine synthase
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what's the pathology/symp of HCU?
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Cataracts
skeletal vascular defects |
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how do you diagnosis HCU?
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Methonine (screen), Homocysteine levels
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MSUD tx?
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restrict: isoleucine
leucine valine *branched chain aa |
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what's the incidence of galactosemia?
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1:35,000
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how's galactosemia transmitted?
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auto recess
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what's the defect in galatosemia?
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Galactose-1-Phosphate Uridyltransferase (Gal-1- PUT)
Phenotypes: N (normal), G (Galactosemia), D (Duarte) GG (0 % activity); DG (25%); GN (50%); DN (75%) *we're really worried about GG |
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what's the pathology/symp of galactosemia?
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Jaundice,
Sepsis (E. coli), acidosis |
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what's the diagnosis of galactosemia?
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Galactose, Galactose-1-Phosphate levels (RBC/serum)
Gal-1-PUT Activity and Phenotype (RBC’s) |
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what's the galactose metabolic pathway?
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where does galactose accumulate in galactosemia?
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liver
*shows w/ PAS stain |
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what's the incidence of congenital adrenal hyperplasia (CAH)?
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1:12,000
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how is CAH transmitted?
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auto recess
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what's the defect in CAH?
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21-Hydrolase - 95% (also 17 and 3-Hydroxylases)
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galactosemia tx?
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restrict: lactose and galactose
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what's the pathology/symp in CAH?
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Adrenal Hyperplasia with Virilization (androgen excess), ambiguous genitalia
Salt-wasting >> hypotension, death |
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how do you diagnose CAH?
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17-OH Progesterone Level
Other hormones, gene typing |
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what's the adrenal steroid synthetic/metabolic pathways? how affected in CAH?
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what's the incidence of MCAD? what kind of disorder is MCAD?
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1: 15,000
fatty acid oxidation disorder |
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what's the defect in MCAD?
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Deficiency of Medium Chain Acyl-CoA dehydrogenase
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what's the clinical finding in MCAD?
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Acidosis, liver dysfunction, coma, death
Sequelae: developmental delay, retardation |
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what are the lab findings for MCAD?
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Abnormal increase in C8 and C10 fatty acids detected by MS/MS
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are there other chain length Acyl-CoA DH deficiencies?
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yes
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MCAD tx?
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feed often and when get sick - monitor closely
give carnitine to stop buildup of fatty acids |
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what are the types of lysosomal storage diseases?
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Sphingolipidoses
sulfatidoses mucopolysaccharidoses mucolipidoses + others |
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what diseases fall under sphingolipidoses?
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GM2 Gangliosidosis: Tay-Sachs (Hexosaminidase A)
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what type of disease is Hurler's disease (alpha-L-Iduronidase)?
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mucopolysaccharidoses
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what diseases fall under sulfatidoses?
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Gaucher Disease (Glucocerebrosidase)
Nieman-Pick Disease (Sphingomyelinase) Metachromatic leukodystrophy (Arylsulfatase A) Krabbe Disease (Galactosylceramidase) Fabry Disease (alpha-Galactosidase A) |
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what's problem w/ lysosome enzyme defect?
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normally, things that go into lysosome are broken into smaller units that leave
if messed up lysosome: can't break down stuff stuff can't leave damages cell func --> cell death |
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which lysosomal storage diseases affect neurologic systems?
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Gangliosides (Tay-Sachs)
Sphingomyelin (Niemann-Pick) Galactosylceramides (Krabbe’s) Glucocerebrosides (Gaucher - juvenile) |
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which lysosomal storage diseases affect hepatic/splenic systems?
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Glucocerebrosides (Gaucher- adult)
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what's the defect in Tay-Sachs? what's result?
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Hexosaminodase A enzyme defect, brain rich in gangliosides
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what pop is there a high incidence of Tay Sachs in?
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Ashkenazic Jewish pops
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what's the prognosis of Tay Sachs?
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Progressive neurologic damage with death at 2-3 years of age
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how do you diagnose Tay Sachs?
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Measure enzyme activity in serum, white cells
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what's the defect in Glucocerebrosides (Gaucher's adult) disease?
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Glucocerebrosidase enzyme defect
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how do you diagnose Gaucher's adult disease?
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WBC’s and RBC’s with glucocerebrosides
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what pop is there an inc incidence of Gaucher's adult?
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High incidence in Eastern European Jewish population
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how does adult Gaucher's disease present?
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Massive hepatosplenomegaly, adult presentation, normal life span
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what's the defect in Tay Sachs? what accumulates?
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Hexosaminidase A: accumulation of gangliosides
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what builds up in Gaucher's adult disease?
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glucocerebrosides
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what are some types of glycogen storage diseases?
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Hepatic: von Gierke Disease
Myopathic: McArdle Syndrome Generalized: Pompe Disease |
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what enzyme is messed up in von Gierke disease?
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Glucose-6-phosphatase
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what symptoms are seen in von Gierke disease?
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Hepatomegaly, hypoglycemia, hyperlipidemia
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what enzyme is messed up in McArdle Syndrome?
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muscle phosphorylase
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what symptoms are seen in McArdle Syndrome?
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Muscular weakness, cramps, normal life span
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what enzyme is messed up in Pompe disease?
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alpha-1,4-Glucosidase
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what symptoms are seen in Pompe disease?
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Diffuse organ involvement, early death
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where in pathway are glycogen storage diseases messed up?
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how do you diagnose / what tests do you do for lysosomal/glycogen storage diseases?
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Enzyme Activity: (synthetic substrates)
Serum, urine Leukocytes Cultured fibroblasts or amniotic fluid cells Gene probes: gene typing Tissue Biopsies: liver, bone marrow, muscle |
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what's the incidence of alpha-1-antitrypsin deficiency?
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Incidence: 1% population with abnormal phenotype (1:7,000 with ZZ)
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how is alpha-1-antitrypsin deficiency transmitted?
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auto recess
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what's the defect in alpha-1-antitrypsin deficiency?
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Deficiency or defective enzyme
Anti-Protease: chymotrypsin, trypsin, plasmin, WBC elastase and collagenase, etc |
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what's the pathology of alpha-1-antitrypsin deficiency?
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Hepatic cirrhosis, pulmonary emphysema
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how do you diagnose alpha-1-antitrypsin deficiency?
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A-1-AT Levels and Phenotype (Immunoassay and IEF)
Pi: MM (100%); MZ (58%); ZZ (15 %); SS (60%); MS (80%) |
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what stain do you use to identify alpha-1-antitrypsin deficiency?
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PAS stain
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what's the incidence of sickle cell anemia?
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1:4,000 (Indiana), 8% carrier rate in black population.
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how is sickle cell anemia inherited?
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auto recess
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what's the defect in sickle cell anemia?
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Amino acid substitution
Abnormal hemoglobin structure |
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what's the pathology of sickle cell anemia?
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Anemia, SS crisis, thrombosis, organ infarcts, infections
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how do you diagnose sickle cell anemia?
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Hgb Phenotyping (electrophoresis)
Gene Defect *see HbF prominent in sickle cell anemia and SC disease |
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what's the incidence of cystic fibrosis?
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1: 2000
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how is cystic fibrosis transmitted?
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auto rec
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what's the defect in cystic fibrosis?
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Sodium/Chloride Ion Transport System
Multiple allele defects - delta F508 (95% in Indiana) Chloride transport across membranes |
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what's the pathology in cystic fibrosis?
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Pulmonary Brochiectasis, Pneumonias, Failure
Hepatic Cirrhosis Malabsorption Infertility meconium ileus: dense, thick stool that needs surgery |
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how do you diagnose cystic fibrosis?
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Trypsinogen level (screen) - increased
Sweat Chloride Test (increased) Gene Defects - 700+ allele variants |
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what's the problem w/ pumps in cystic fibrosis?
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normal: body pumps Cl- back in and Na+ follows.. skin not so salty
cf: Cl- can't be in.. Cl- stays outside w/ Na+ ... skin salty normal: Cl- pumped out into airway and some Na+ and H2O goes into cell cf: Cl- not pumped out into airway.. pulls Na+ and H2O into cell --> more mucus -> bronchiecstases |
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what is incidence of hemochromatosis?
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1:400 (whites, western europe)
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what's the transmission of hemochromatosis?
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auto recess
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what's the etiology of hemochromatosis?
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Primary - hereditary disorder, excessive iron absorption
Secondary - excessive iron overload states, example: beta-thalassemia with multiple transfusions |
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what are the anatomical findings in hemochromatosis?
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Micronodular cirrhosis - iron deposits
Diabetes - iron deposits in Islets, fibrosis Skin pigmentation - increased melanin |
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how do you diagnose hemochromatosis?
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Iron levels, blood and liver
Gene defect (s) |
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cystic fibrosis tx?
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pulmonary toilet: pound on back and beat secretions free
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