Enzyme and Immunodeficiencies Flashcards
X-linked immunodeficiencies
- Wiskott-Aldrich Syndrome
- Bruton’s Agammaglobulinemia
- Chronic Granulomatous disease
- Hyper IgM syndrome (no CD ligand)
Adenosine Deaminase deficiency
SCID
Absent HGPRT
Lesch-Nyhan syndrome
- defective purine salvage
- X-linked recessive
Defective nucleotide excision repair leads to what disorder
Xeroderma pigmentosum
- can’t repair pyrimidine dimers
- ssDNA repair failure
What DNA repair mechanism is defective in Hereditary non polyposis colorectal cancer
Mismatch repair
-failure to recognize and remove mismatched nucleotides in newly synthesized DNA strand
What DNA repair mechanism is defective in Ataxia Telangiectasia
Nonhomologous end joining
-failure to bring ends of DNA fragments together to repair double stranded breaks
Anti-Smith antibodies
Antibodies to spliceosomal snRPs
-SLE
Anti-U1 RNP antibodies
Mixed connective tissue disease
Defect in phosphotransferase
I-cell disease: inclusion cell disease
-inherited lysosomal storage disorder d/t failure of Golgi to phosphorylate mannose residues (decr. M6P) so can’t traffic proteins to lysosomes so they get secreted extraceullarly
The clinical features of I cell disease are similar to what?
Mucopolysaccharidoses
-Hunters, Hurlers
Coarse facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes, mental retardation may be present
I cell disease
Pathogenic states with Cytoplasmic inclusions
- Lysosomal storage disease
- I-cell disease
- Mucopolysaccharidoses
- Chediak-Higashi syndrome
- Alzheimer’s disease
- Parkinson’s disease
- CMV
- Rabies virus
- Herpes virus
Defective a-chain of IV collagen
Alport syndrome
Lack of hydroxylation of proline and lysine residues of pre-procollagen
Scurvy d/t Vitamin C deficiency
-Vitamin C is necessary for hydroxylation
Deficient formation of procollagen
Osteogenesis imperfecta
- deficient formation of triple helix of procollagen
- decr. production of normal type I collagen
Defective formation of collagen fibrils d/t inability to form cross-linkages (lysine-hydroxylysine)
Ehlers-Danlos
Decr. activity of lysyl oxidase is caused by
Impaired copper absorption and transport
-Menkes disease: brittle, kinky hair, growth retardation, hypotonia; d/t deficient formation of lysine-hydroxylysine cross linkages
Autosomal dominant diseases
- ADPKD
- FAP
- Familial hypercholesterolemia
- Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)
- Hereditary spherocytosis
- Huntington disease
- Marfan syndrome
- MEN
- NF-1 (von Recklinghausen disease)
- NF-2
- Tuberous sclerosis
- vHL
Autosomal Recessive diseases
- Albinism
- ARPKD
- Cystic fibrosis
- Glycogen storage diseases
- Hemochromatosis
- Kartagener syndrome
- Mucopolysaccharidoses (except Hunter syndrome)
- PKU
- Sickle cell anemia
- Sphingolipidoses (except Fabry disease)
- Thalassemias
- Wilson’s disease
X-linked recessive disorders
- Bruton agammaglobulinemia
- Wiskott-Aldrich syndrome
- Fabry Disease
- G6PD deficiency
- Ocular albinism
- Lesch-Nyhan syndrome
- Duchenne and Becker Muscular dystrophies
- Hunter Syndrome
- Hemophilia A and B
- Ornithine transcarbamylase deficiency
Trinucleotide repeat expansion diseases
- Huntington disease (CAG)
- Myotonic dystrophy (CTG in DMPK gene)
- Friedreich ataxia (GAA)
- Fragile X syndrome (CGG in FMR1 gene)
Autosomal Trisomies
- Down syndrome (trisomy 21)
- Edwards syndrome (trisomy 18)
- Patau syndrome (trisomy 13)
Prader-Willi Syndrome
Maternal imprinting: Paternal gene is deleted/mutated and maternal gene is silent; PATERNAL gene problem
-hyperphagia, obesity, intellectual disability, hypogonadism, hypotonia
Angelman Syndrome
Paternal imprinting: Maternal gene is deleted/ mutated and paternal gene is silent; MATERNAL gene problem
-inappropriate laughter, seizures, ataxia, severe intellectual disability
If a patient is manifesting an autosomal recessive disorder but only one parent is a carrier, consider what genetic abnormality
Uniparental disomy
-offspring receives 2 chromosomes from one parents and none from the other
Inherited disorder that leads to incr. phosphate wasting at proximal tubule
Hypophosphatemic rickets (rickets-like presentation) -X-linked dominant; (Vit. D-resistant rickets
Mitochondrial myopathies
myopathy, lactic acidosis, CNS disease secondary to failure in oxidative phsophorylation
-ragged red fibers seen on muscle biopsy
Quad screen for Down Syndrome
decr. AFP and estriol
incr. B-hCG and inhibin A
Quad screen for Edwards syndrome
decr. AFP, estriol, B-hCG
decr. or normal inhibin A
