Genetic Disorders: Autosomal recessive and X-linked (includes Lysosomal storage dz) Flashcards
Fabry’s disease –> enzyme def and what builds up; inheritance pattern
(sphingolipidosis, along w/ Gauchers, Niemann pick, Tay-sach, krabes and metachromic leukodystrophy)
- α-galactosidase A
- ceramide trihexoside
- X-linked recessive
Symptoms of Fabry’s disease (5)
- peripheral neuropathy hands/feet
- g.i. pain (fat build up in vessels–> ischemia)
- renal failure
- HTN
- cardiomyopathy
Gaucher’s disease; enzyme def. and waht builds up
- Glucocerebrosidase
- Glucocerebroside
- AR (most common of lysosomal storage dz)
Symptoms of Gaucher’s (2)
- Hepatosplenomegaly–> lead to anemia and thrombocytopenia
2. bone crises (including aseptic necrosis of bone)
microscopic fining in Gaucher’s
Macrophages swollen with blue cytoplasmic debris (fibrils)–> look like “tissue paper”, light blue staining
Niemann-Pick disease–> enzyme def. and accumulation
- sphingomyelinase
- sphingomyelin
*is AR
symptoms/ finding of Niemann-Pick (4)
- neurodegen (ataxia, dysarthri, dysphagia; affects cerebellum)
- hepatosplenomegaly
- cherry-red spot on macula
- foam cells
Tay-Sach’s disease–> enzyme def. and accumulation
- hexosaminidase A
- GM2 ganglioside
*AR
symptoms/ findings of Tay-Sach’s
- progressive neurodegeneration and developmental delay
- cherry-red spot on macula
- NO HEPATOSPLENOMEGALY (dist. from Niemann-pick)
- lysosomes w/ onion skin
Krabbe’s dz–> enzyme def. and accumulation
- Galactocerebrosidase
- Galactocerebroside
*AR
symptoms/ finding of Krabbe’s dz
- Peripheral neuropathy
- developmental delay
- optic atrophy
- globoid cells
(muscle wasting, progressive weakness, vision loss, dementia); is a demyelinating dz
*pt. usually dead by age 2
Metachromic leukodystrophy enzyme def. and accumulation
- Arylsulfatase A
- Cerebroside sulfate
*AR
symptoms of Metachromic leukodystrophy
similar to Krabbe’s–> muscle wasting, weakness, vision loss, dementia; but prob more central involvment (demyelination) like ataxia
Huler’s syndrome–> enyme def. and acuumulation
- α-L- iduronidase
- heparan sulfate, dermatan sulfate
*AR; is a mucopolysaccharidosis
symptoms of Hurler’s dz (5)
- developmental delay
- gargoylism (short stature, coarse facies)
- Corneal clouding
- hepatosplenomegaly
- airway obstruction
Hunter’s syndrome–> enzyme def. and acumulation; inheritance
- Iduronate sulfatase
- Heparan sulfate, dermatan sulfate
*x-linked recessive
Main way to tell Hunter’s from hurlers, since presentation is otherwise same
Hunter’s has NO corneal clouding and is X-linked recessive
“Hunters see clearly and aim for the X”
mutated gene in cystic fibrosis, what chromosome
CFTR 1 gene, chromosome 7
6 symptoms of CF
- recurrent pulmonary infections
- chronic bronchitis
- bronchiectasis
- pancreatic insufficiency (failure to thrive)
- Meconium ileus in newborn
- nasal polyps
what two agents are responsible for recurrent bacterial infection in CF pts
- Pseudomonas
2. S. aureus
what causes some CF infants to present with failure to thrive
fat soluble vitamin deficiencies due to malabsorption form pancreatic insufficiency
issue males with CF have
infertility–> bilateral absence of vas deferens
Tx for CF?`
N-acetylcysteine (breaks up mucous by cleaving disulfide bonds
what Abx given for CF bacterial infections
fluoroquinolones
10 X-linked recessive disorders
“Oblivious Female Will Give Her Boys x-Linked Disorders”
- one has two dz
- Ocular albinism/ Ornithine Transcarbmoylase
- Fabry’s dz.
- Wiskott-Aldrich syndrome
- G6PD deficiency
- Hemophilia A and B
- Bruton’s agammaglobulinemia
- Hunter;s syndrome
- Lesch-Nyhan syndrome
- Duchenne (and Beckers) Muscular dystrophy
