Some Genetic Diseases from First Aid Biochem Flashcards
Achondroplasia
autosomal dominant mutation in FGFR3 inhibits chondrocyte proliferation. Full penetrance.
ADPKD
bilateral enlargement of kidneys due to cysts. 85% of cases are due to mutation in PKD1 (chromosome 16, 16 letters in “polycystic kidney”). Remainder due to PKD2. Autosomal dominant.
FAP
familial adenomatous polyposis. colon becomes covered with adenomatous polyps after puberty. Colon must be resected or 100% progress to colon cancer. Mutation is at chromosome 5q (APC gene) (5 letters in “polyp”). Autosomal dominant.
Familial Hypercholesterolemia
Elevated LDL due to due to defective or absent LDL receptor. Severe atherosclerotic disease early in life, corneal arcus, tendon xanthomas (classically the achilles tendon). Autosomal dominant.
Hereditary Hemorrhagic Telangiectasia
telangiectasias, recurrent epistaxis, skin discoloration, AVMs, Gi bleeding, hematuria. AKA Osler-Weber- Rendu syndrome. Autosomal dominant.
Huntington Disease
depression, progressive dementia, choreiform movements, caudate atrophy. Trinucleotide repeat disorder of gene on chromosome 4 (CAG repeats). Autosomal dominant with anticipation. increase number of repeats, decrease age of onset.
Li-Fraumeni syndrome
abnormalities in TP53. multiple malignancies at an early age. Also known as SBLA cancer syndrome (sarcoma, breast, leukemia, adrenal gland). Autosomal dominant.
Marfan syndrome
FBN1 mutation on chromsome 15 leading to defective fibrillin (the scaffold for elastin. Tall with long extremities, pectus excavatum, hypermobile joints, tapering of fingers and toes (arachnodactyly); cystic medial necorsis of the aorta. Aortic incompetence leads to dissection. Autosomal dominant.
MEN
MEN 1 associated with MEN1 gene. MEN 2A and 2B associated with RET gene. Autosomal dominant.
MEN1
hyperparathyroidism
pituitary adenoma
pancreatic tumors (especially
MEN 2A
hyperparathyroidism
pheochromocytoma
medullary thyroid cancer
MEN 2B
marfan
medullary thyroid cancer
pheochromocytoma
NF1
cafe-au-lait spots, cutaneous neurofibromas, optic gliomas, pheo, Lsich nodules (pigemented iris hamartomas). 100% penetrance, variable experssion. autosomal dominant . mutation on NF1 gene on chromomsome 17. 17 letters in von Recklinghausen.
NF2
bilateral acoustic schwannoma, juvenile cataracts, NF2 gene on chromsome 22. 2 –> 22. autosomal dominant.
Tuberous Sclerosis
Neurocutaneous disorder. autosomal dominant.
von Hippel-Lindau disease
characterized by the development of numerous tumors. both benign and malignant. associated with deletion of VHL gene (tumor suppressor) on chromosome 3P. 3 words Von hippel lindau –> chromosome 3.
some autosomal recessive diseases
albinism, cystic fibrosis, glycogen storage disease, hemochromatosis, kartegener syndrome, PKU, sickle cell anemia, thalassemias, Wilson disease
Cystic Fibrosis - genetic defect
CFTR gene defect on chromsome 7. often deletion of Phe508. most common lethal genetic disease in caucasian population.
Cystic Fibrosis - pathophysiology
CFTR codes for ATP gated Cl channel. This channel secretes Cl in lungs and GI tract, reabsorbs Cl- in sweat glands. Phe508 deletion leads to misfolded protein, protein retained in RER, leading to decreased Cl (and H2O) secretion. Abnormally thick mucus secreted in the lungs.
Cystic fibrosis - complications
recurrent pulmonary infections (staph aureus in infancy and pseudomonas as teenager).
pancreatic insufficiency. malabsorption, A, D, E, K vitamin deficiency (fat soluble).
Infertility in men
nasal polyps and clubbing of nails
cystic fibrosis - diagnosis
chloride sweat test (>60 meq)
X-linked recessive disorders (w/ mnemonic)
Oblivious Female Will Often Giver Her Boys Her x-Linked Disorders Ornithine transcarbamylase deficiency Wiskott-Aldrich Ocular albinism G6PD Hunter syndrome Bruton agammaglobulinemia Hemophilia A and B Lesch Nyhan Syndrome Duchenne (and becker muscular dystrophy)
Duchenne Muscular dystrophy
- cause
- clinical findings
- lab findings
- diagnosis
frameshift or nonsense mutation leading to truncated dystrophin, inhibited muscle regeneration.
- pseudohypertrophy of the calves
- gower
increase CK and aldolase are seen. Western blot and muscle biopsy confirm the diagnosis.
Becker muscular dystrophy
due to non frameshift insertions in dystrophin gene. partially. leads to a partially functional protein. less severe disease course. onset in teenage years or early adulthood instead of early childhood.
