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143 Cards in this Set
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- Back
- 3rd side (hint)
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Question
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Answer
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Hint
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fabry's dz: inheritance
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XR
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fabry's dz: deficient enzyme and accumulation
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alpha-galactosidase A ceramide trihexoside
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fabry's dz: clinical
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peripheral neuropathy of hands and feet angiokeratomas CV/renal dz
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gaucher's dz: inheritance
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AR
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gaucher's dz: deficient enzyme and accumulation
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glucocerebrosidase glucocerebroside
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gaucher's dz: clinical
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crumpled tissue paper type 1: erosion of femoral head, hepatosplenomegaly, mild anemia; gaucher cells in liver, spleen, lymph nodes, bone marrow type 2: infantile; severe CNS involvement, seizures, mental deterioration, death by 1 yr type 3: juvenile, less severe than type 2
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neimann-pick dz: inheritance
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AR
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neimann-pick dz: deficient enzyme and accumulation
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sphingomyelinase sphingomyelin
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neimann-pick dz: clinical
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cherry-red spot on macula hepatosplenomegaly anemia death by 3 yrs FOAMY HISTIOCYTES in liver, spleen, lymph nodes, skin
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tay-sachs dz: inheritance
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AR
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tay-sachs dz: deficient enzyme and accumulation
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hexosaminidase A GM2
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tay-sachs dz: clinical
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cherry-red spot mental/motor deterioration blindness death before 4 yrs
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krabbe's dz: inheritance
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AR
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krabbe's dz: enzyme defiency and accumulation
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beta-galactosidase beta-galactoside
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krabbe's dz: clinical
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peripheral neuropathy developmental delay optic atrophy
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metachromatic leucodustrophy: inheritance
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AR
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metachromatic leucodustrophy: enzyme defiency and accumulation
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arylsulfatase A cerebroside sulfate
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metachromatic leucodustrophy: clinical
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demyelination of CNS and pns ataxia dementia
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hurler's syndrome: inheritance
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AR
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hurler's syndrome: enzyme deficient and accumulation
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alpha-L-iduronidase heparan sulfate and dermatan sulfate
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hurler's syndrome: clinical presentaion
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BALLOON CELLS in heart, liver, brain gargoylism cardiomegaly corneal clouding airway obstruction MR
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hunter's syndrome: inheritance
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XR
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hunter's syndrome: enzyme deficiency and accumulation
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iduronidase sulfate heparan sulfate and dermatan sulfate
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hunter's syndrome: clinical presentation
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hepatosplenomegaly aggressive behavior no corneal clouding
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glycogen storage dzs (names)
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Very Poor Carbohydrate Metabolism I: von gierke's II: pompe's III: cori's V: McArdle's
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von gierke's dz
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glucose 6 phosphatase deficiency liver becomes muscle lactic acid in liver hepatomegaly increased glycogen in liver convulsions and severe hypoglycemia
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pompe's dz
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deficiency in alpha-1,4 glucosidase cardiomegaly death from cardiorespiratory failure by 3 yo
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cori's dz
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deficiency in alpha 1,6 glucosidase milder form of type 1, but with normal lactose levels
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McArdle's dz
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glycogen phosphorylase deficiency increased glycogen in muscle that can't be broken down painful muscle cramps myoglobinuria with strenuous exercise
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PKU
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can't convert phe --> tyr b/c of phenylalanine hydroxylase deficiency (or tetrahydrobiopterin cofactor defic) --> musty body odor, light colored skin, MR low phenylalanine diet, with high tyrosine
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Alkaptonuria Clinical
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Urine turns black on standing. CT also black. May have debilitating arthralgia
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Alkaptonuria Cause
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Def homogentistic acid oxidase (tyrosine metab)
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Albinism cause
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1. def tyrosinase (can’t make melanin)(AR) 2. Defective tyrosine transporter May result from lack of migration of neural crest cells
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Homocystinuria cause
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1. Cystathionine synthase def (tx dec met, inc cys) 2. dec affinity of Cystathionine synthase for B6 (tx inc inc B6) 3. Met synthase def
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3 causes
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Homocystinuria clinical
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Mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation(down and in), atherosclerosis (stroke, MI)
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Cystinuria cause
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Defective renal tube transporter of Cys, Ornithine, Lys, Arg (COLA)
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COLA
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Cystinuria clinical
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Excess cys in urine may cause cys kidney stones
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Cystinuria tx
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Acetazolamide to alkanize urine
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Try to alkanize urine
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MSUD cause
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Alpha-ketoacid dehydrogenase def. Can’t metab branched chain aa’s (val, leu, ile)
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I Love Vermont maple syrup
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MSUD clinical
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Severe CNS defects, mental retardation, death. Affect kids (poor appetite, irritability, and the characteristic odor of the urine. Within days they lose their sucking reflex and grow listless, have a high-pitched cry, and become limp with episodes of rigidity)
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ADA def clinical
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SCID
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Bubble boy
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Lesch-Nyhan syndrome clinical
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Retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis
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Lesch-Nyhan syndrome cause
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Def of HGPRTase -> excess uric acid (Hypoxanthine-Guanine Phosphoribosyl Transferase)
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Purine salvage pathway
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Prader-Willi
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Imprinted paternal gene. Retardation, obesity, hypoganadism, hypotonia
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Angleman’s synd
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Imprinted maternal gene. Retardation, seizures, ataxia, inappropriate laughter (happy puppet)
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What is the mechanism of Prader-Willi syndrome?
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No copies of 15q11 have PATERNAL imprinting. P = Prader Willi (Both imprinted genes are necessary function. A patient can fail to inherit a properly imprinted 15q11 from one parent, as a result either of deletion of the 15q11 region from that parent's chromosome 15 or from uniparental disomy, in which both copies have been taken from the other parent's genes.)
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FA114
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What is the mechanism of Angelman's syndrome?
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No copies of 15q11 have MATERNAL imprinting. Angel = mother (Both imprinted genes are necessary function. A patient can fail to inherit a properly imprinted 15q11 from one parent, as a result either of deletion of the 15q11 region from that parent's chromosome 15 or from uniparental disomy, in which both copies have been taken from the other parent's genes.)
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FA114
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What are the clinical manifestations of Prader-Willi syndrome?
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1. Mental retardation; 2. Obesity; 3. Hypogonadism; 4. Hypotonia
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FA114
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What are the clinical manifestations of Angelman's syndrome?
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1. Mental retardation; 2. Seizures; 3. Ataxia; 4. Inappropriate laughter (happy puppet)
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FA114
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What are the common autosomal dominant diseases?
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"Hardly Have Focus Now? Avoid FM And TV" 1.Huntingtons; 2. Hereditary spherocytosis; 3. Familial adenomatous polyposis; 4. Neurofibromatosis 1 and 2; 5.Adult polycystic kidney disease; 6. Familial hyperchoelsterolemia (type IIA); 7. Marfan's syndrome; 8. Achondroplasia; 9. Tuberous sclerosis; 10. Von Hippel-Lindau disease;
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FA116
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How does adult polycystic kidney disease present?
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1. BILATERAL enlargement of both kidneys; 2. Pain; 3. Hematuria; 4. HYPERTENSION;
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FA119
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What is the gene in adult polycystic kidney disease?
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APKD1 (chromosome 16)
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FA119
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What are the 3 associations of adult polycystic kidney disease?
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1. Liver cysts 2. Berry aneurysms 3. Mitral valve prolapse
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FA119
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What is the mode of inheritance of Huntingtons
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Autosomal dominant
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FA119
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What is the mode of inheritance of Hereditary spherocytosis
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Autosomal dominant
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FA119
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What is the mode of inheritance of Familial adenomatous polyposis
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Autosomal dominant
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FA119
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What is the mode of inheritance of Neurofibromatosis 1
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Autosomal dominant
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FA119
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What is the mode of inheritance of Neurofibromatosis 2
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Autosomal dominant
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FA119
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What is the mode of inheritance of Adult polycystic kidney disease
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Autosomal dominant
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FA119
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What is the mode of inheritance of Familial hyperchoelsterolemia (type IIA)
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Autosomal dominant
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FA119
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What is the mode of inheritance of Marfan's syndrome
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Autosomal dominant
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FA119
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What is the mode of inheritance of achondroplasia
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Autosomal dominant
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FA119
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What is the mode of inheritance of Tuberous sclerosis
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Autosomal dominant
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FA119
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What is the mode of inheritance of Von Hippel-Lindau disease
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Autosomal dominant
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FA119
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What is the cholesterol level in heterozygotes with familial hyperchoelsterolemia (type IIA)?
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Three hundred
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FA119
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Why is the cholesterol level in homozygotes with familial hyperchoelsterolemia (type IIA)?
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Seven hundred
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FA119
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MI develops before age 20, what is the possible dx?
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familial hypercholesterolemia (type IIA)
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FA119
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What are the skeletal abnormalites associated with Marfan's?
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1. Arachnodactyly ("spider fingers" ); 2. Pectus excavatum; 3. Hyperextensive joints
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FA119
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What are the cardiovascular findings in Marfan's?
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1. Cystic medial necrosis (weakening of media leading dissection of the aorta); 2. aortic incompentence; 3. floppy mitral valve
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FA119
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What are the ocular findings in Marfan's?
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Subluxation of the lens
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FA119
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What is the defect in NF1?
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Mutation neurofibromin gene of chromosome 17. The neurofibromin gene (NF1) is a negative regulator of the Ras oncogene.
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FA119
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What are the seven findings in NF1?
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1. café-au-lait spots; 2. neural tumors; 3. Lisch nodules ; 4. scolosis; 5. optic pathway gliomas; 6. pheochromocytomas; 7. increased tumor susceptiblity
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FA119
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What is the defect in NF2?
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NF2 gene on chromosome 22 (NF2=22)
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FA119
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What are the two classic findings in NF2?
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1. Bilateral acoustic neuromas (crainal nerve 8); 2. juvenile cataracts
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FA119
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What is tuberous sclerosis? (just read)
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Multi-system genetic disease that causes benign tumours to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin
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FA119
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What are the 7 findings in tuberous sclerosis?
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1. Adenoma sebaceum (raised, red papules on the face, mainly about the nose) 2. hypopigmented "ash leaf spots" on skin 3. cortical and retinal hamartomas 4. seizures 5. mental retardation 6. renal cysts 7. cardiac rhabdomyomas
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FA119
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What genetic pattern does tuberous sclerosis display?
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Incomplete penetrance and variable presentation
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FA119
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What is the defect associated with Von Hippel-Lindau disease?
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Deletion of VHL gene (tumor suppressor) on chromosome 3 (there are three words in van hippel-lindau)
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FA119
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What are the 2 findings in Von Hippel-Lindau disease?
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Hemangioblastomas of retina/cerebellum/medulla Half develop renal cell carcinoma
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FA116
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What are the findings in Huntington's disease?
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1. Depression; 2. Dementia; 3. Choreiform movements (jerky, random, uncontrollable, rapid movements); 4. Caudate atrophy
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FA119
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What are the neurotransmitter findings in Huntington's disease?
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Decreased levels of GABA and Ach in the brain
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FA119
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When do symptoms of Huntington's manifest?
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Ages of 20-50
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FA119
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Where is the defect in huntington's?
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trinucleotide repeat expansion in the Huntingtin (Htt) gene located in chromosome 4. This expansion produces an altered form of the Htt protein, mutant Huntingtin (mHtt), which results in neuronal cell death in select areas of the brain and is a terminal illness. "Hunting 4 food"
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FA119
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Where is the defect in familial adenomatous polyposis?
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Chromosome 5 - "Polyp" has five letters in it
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FA119
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What are the 2 clinical manifestations of familial adenomatous polyposis?
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1. Colon covered with polyps after puberty 2. 100% progression to cancer unless resected
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FA119
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What is the defect in hereditary spherocytosis?
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defects in the genes that code for spectrin, ankyrin, protein 4.1, and other erythrocyte membrane proteins
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FA119
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Increased or decreased MCHC?
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Increased
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FA119
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How do you cure hereditary spherocytosis?
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splenectomy
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FA119
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What is the defect in achondroplasia?
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Mutation in the fibroblast growth factor receptor gene 3 (FGFR3). FGFR3 normally has a negative regulatory effect on bone growth. In achondroplasia, the mutated form of the receptor is constitutively active and this leads to severely shortened bones.
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FA119
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Where do new mutation that lead to achondroplasia come from?
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New gene mutations are associated with increasing paternal age (over 35 years)
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FA119
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What are the important autosomal recessive diseases?
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"HAG PLASTIC" 1. Hemochromatosis; 2. Albinism; 3. Glycogen storage; 4. Phenylketonuria; 5. Lysosomal storage (except 2); 6. alpha-antitrypsin deficiency; 7. Sickle cell; 8. Thalassemias; 9. Infant polycystic kidney disease; 10. Cystic fibrosis;
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FA119
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What is the defect in cystic fibrosis?
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CFTR gene on chromosome 7 (deletion of Phe 508), what does the channel do?
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Secretes Cl- in lungs and GI tract and reabsorbs Cl- from sweat
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What is the diagnositc test for cystic fibrosis?
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Increased Cl- in sweat
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FA119
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What is the pathogenesis of cystic fibrosis?
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Defective Cl- channel secretes abnormally thick mucus that plugs 1. lungs; 2. pancreas; and liver
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FA119
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What are the clinical findings in cystic fibrosis?
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1. Recurrent pulmonary infections (Pseudomonas species and S.Aureus); 2. Chronic bronchitis; 3. Bronchiectasis; 4. Pancreatic insufficiency (malabsorption and steatorrhea); 5. Menconium ileus in newborns (meconium becomes thickened and congested in the ileum)
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FA119
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Cystic fibrosis causes infertility how?
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MEN - absent vas deferens; WOMEN - thickened mucus (97% of men are infertile)
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FA119
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How can CF present in newborns? In infancy?
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Newborn - menconium illeus; 2. infants - failure to thrive
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FA119
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What is the most common lethal genetic disease of caucasians?
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Cystic fibrosis
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FA119
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What is the treatment for cystic fibrosis?
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N-acetylcysteine - loosens mucus plugs
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FA119
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What are the X-linked recessive diseases?
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"Be Wise, Fools GOLD, Heeds False Hope"; 1. Bruton's agammaglobulinemia; 2. Wiskott-Aldrich syndrome; 3. Fragile X; 4. G6PD deficiency; 5. Ocular albinism; 6. Lesch-Nyhan syndrome; 7. Duchenne's muscular dystrophy; 8. Hemophila A/B; 9. Fabry's diease; 10. Hunter's syndrome
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FA119
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What are the two types of muscular dystrophy?
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Duchenne's and Beckers
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FA119
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What is the defect in Duchenne's muscular dystrophy?
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FRAMESHIFT mutation that leads to the deletion of the dystrophin gene, what does this cause?
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The absence of dystrophin leads to muscular cell death, which is replaced by fatty tissue.
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What is the age of onset of DMD?
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before 5 years
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FA119
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How does DMD progress?
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Begins in pelvic girdle muscles and progresses superiorly
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FA119
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What are the 3 symptoms of DMD?
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1. Proximal muscle weakness 2. Pseudohypertrophy of the calf (due to replacement of muscle with fat) 3. Cardiac myopathy
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FA119
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What is the manuever that requires assistance of the upper extremites to stand?
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Gower's maneuver
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FA119
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What is the defect in Beckers muscular dystrophy?
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Dystropin gene (just like DMD) but there isnt a complete lack of the protein, making Becker's less severe
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FA119
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How do you diagnose muscular dystrophies?
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Increased CPK and muscle biopsy
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FA119
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What is the defect in Fragile X?
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Expansion of the CGG repeating codon that leads to METHYLATION of that portion of the DNA. This causes the SILENCING of the FMR1 gene.
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FA119
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What are the first and second most common causes of mental retardation?
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1. Down's syndrome; 2. Fragile X
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FA119
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What are the 3 signs of Fragile X?
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"Fragile X" 1. X-large testes 2. X-large jaws and ears 3. Autism
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FA119
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What are the four trinucleotide repeat expansion diseases?
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"Try (tri) HUNTing for MY FRIEd eggs (X)" 1. Huntington's; 2. Myotonic dystrophy; 3. Friedreich's ataxia; 4. Fragile X
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FA119
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What are characteristics for diseases with anticipation?
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Increased disease severity, decreased age of onset with each subsquent generation
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FA119
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What is myotonic dystrophy (read)?
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Tri nucleotide disease characterized by a wasting of the muscles (muscular dystrophy), posterior subcapsular iridescent cataracts (opacity of the lens of the eyes), heart conduction defects, endocrine changes and myotonia (difficulty relaxing a muscle). (Not described in FA, but mentioned under the trinucleotide repeat disorders)
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FA119
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What is the number one cause of congential malformations in US?
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Fetal alcohol syndrome
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FA119
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When is the highest risk for congential malformations due to FAS?
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3-8 weeks
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FA119
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What are the 5 malformations associated with fetal alcohol syndrome?
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1. Retardation 2. Microcephaly 3. Facial abnormalities 4. Limb dislocation 5. Heart and lung fistulas
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FA119
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What are the symptoms of 22q11 microdeletion?
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CATCH-22 - Cleft palate, Abnormal facies, Thymic aplasia, Cardiac defects, Hypocalemia (secondary to parathyroid aplasia)
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FA118
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Cleft palate, Abnormal facies, Thymic aplasia, Cardiac defects, Hypocalemia (secondary to parathyroid aplasia) is associated with what?
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Microdeletion of 22q11
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FA118
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What is DiGeorge syndrome?
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Microdeletion of 22q11 leads to 1. Thymic aplasia; 2. Parathyroid aplasia; 3. Cardiac defects
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FA118
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What is the defect in DiGeorge syndrome?
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Microdeletion of 22q11
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FA118
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What is Velocardiofacial syndrome?
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Microdeletion of 22q11 leads to 1. Cleft palate; 2. Abnormal facies; 3. Cardiac defects
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FA118
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What is the defect in Velocardiofacial syndrome?
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Microdeletion of 22q11
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FA118
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What are the three trisomies?
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1. Down syndrome (trisomy 21 - drinking age); 2. Edward's syndrome (trisomy 18 - election age); 3. Patau's syndrome (trisomy 13 - age of puberty)
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FA118
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What is the prevalence of down syndrome?
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1 in 700
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FA118
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What is the prevalence of edward's syndrome?
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1 in 8000
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FA118
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What is the prevalence of patau's syndrome?
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1 in 15000
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FA118
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What are the findings in patau's syndrome?
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1. Mental retardation; 2. Microphthalmia (small eyes), single eye; 3. Microcephaly; 4. CLEFT lip/palate; 5. Abnormal forebrain structures; 6. Polydactyly (extra digit); 7. Congential heart disease
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FA118
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When does death occur patients with Edward's and Patau?
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Within 1 year of birth
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FA118
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What are the clinical findings in Edward's syndrome (trisomy 18)?
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1. Mental retardation; 2. Rocker bottom feet; 3. Low-set ears; 4. Micrognathia (small jaw); 5. Congential heart disease; 6. Clenched hands; 7. Prominent occiupt
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FA118
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What are the clinical findings of Down Syndrome?
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1. Retardation; 2. Flate facial profile; 3. Prominent epicanthal folds (skin fold of the upper eyelid); 4. Simian crease; 5. Duodenal atresia; 6. congential heart disease (septum primum type ASD due to endocardial cushion defects); 7. Alzheimer's disease in those >35
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FA118
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What cancer is associated with Down syndrome?
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Increased risk of ALL
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FA118
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What causes trisomy 21?
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95% - Meiotic nondisjunction of homologous chromosomes; 4% due to Robertsonian translocation; 1% Down mosacisim
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FA118
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What is a Robertsonian translocation?
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Two nonhomologous acrocentric chromosomes (chromosomes with centromeres near their ends) break at their centromeres. The long arms from the different chromosomes join, and the short arms join (reciprocal product).
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FA118
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How does a Robertsonian translocation cause down syndrome?
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The long arm of 21 joins with the long arm of 14. The carrier is fine, but the progeny of this carrier may inherit an unbalanced trisomy 21, causing Down Syndrome
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FA118
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What is Down mosaicism?
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Some cells of the body have trisomy 21, and some have the typical number of chromosomes
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FA118
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What is the maternal association with down syndrome?
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1:1500 for women under 20 to 1:25 for women >45
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FA118
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What are three screening tests for down syndrome?
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1. Decreased levels of alpha-fetoprotein 2. Increased levels of beta-HCG; 3. Ultrasound shows NUCHAL TRANSLUCENCY
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FA118
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What results when non-disjunction occurs in Anaphase I?
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2 gametes with extra chromatids; 2 without any
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FA118
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What results when non-disjunction occurs in Anaphase II?
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2 normal gametes; 1 gamete with no chromatid; 1 gamete with an extra chromatid
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FA118
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What is the defect in Cri-du-chat?
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Deletion of short arm (p) of chromosome 5
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FA118
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What are the findings associated with Cri-du-chat?
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1. Microcephaly; 2. Mental retardation; 3. High-pitched crying; 4. Epicanthal folds; 5. Cardiac abnormalities
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FA118
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