Diseases for FOM final Flashcards
Werner’s Syndrome
Symptoms - premature aging, cancer at several sites, genome instability Cause - Enzyme defects in 3’ exonuclease function and DNA helicase
Essential fructosuria
Beneign defeciency in fructokinase leads to false positives in diabetes urine testing
Turner’s Syndrome
1/5000 x deletion in females.
Symptoms - acute hepatic crisis, similar to HHH, begin 2-4 months after birth, jaundice, hepatomegaly, elevated AST/ALT, hypoglycemia, succinylacetone in blood Causes - disorder in fumaryloacetoacetate hydrolase (FAH) Treatment - Nitosinone - prevents production of homogentisate
Tyrosinemia I
Symptoms - high fluid pressure and lens glycosylation of eye. Blindness and vision loss. Causes - hyperglycemia (glucose fructose or galactose) causing sugars to utilize the polyol pathway which causes high concentrations of fructose and sorbitol in the eye –> increased osmotic pressure and non-enzymatic glycosylation of the lens
Cataracts
Phenylketonuria (PKU)
Symptoms - siezures, cognitive delay, light complexion, mousy odor, high phenylalanine and low tyrosine Causes - disorder with enzyme that converts phe to tyr Treatments - low phe diets
1/5000 x deletion in females.
Turner’s Syndrome
Symptoms - benign or malignant growths of tissues such as hair, muscle, bits of teeth etc. Cause - uncontrolled growth of germ cells.
Teratocarcinomas
Severe combined immunodeficiency (SCID)
Symptoms - lymphocytes below 500/ml3, costochondral junction dysplasia Causes - defeciency of adenosine deaminase (ADA) –> accumulation of 2-deoxyadenosine –> toxic to lymphocytes Treatment - bone marrow transplant, chemotherapy
Symptoms - autism/siezure disorder Causes - hyperactive branch chain breakdown enzymes Treatment - High BCAA diet
Familial Autism
1/1000 males, caused by extra copies of xxy
Klinefelter’s Syndrome
Ryanidine becomes unbound in the presence of halothane or other anesthetics resulting in continuous calcium pumping. Burning of ATP for this gives off heat.
Malignant Hyperthermia
Prader-Willi Syndrome (PWS)
Symptoms - developmental mental retardation Causes - PW is silenced on maternal gene, so if mutation occurs on paternal gene disease is expressed due to missing gene. If maternal imprinting problems of PW gene overactivity causes disease as well. NEED ONE ACTIVE SNORD GENE.
squamous cell carcinoma
malignant epithelial neoplasm showing squamous differentiation
Eptsein-Barr Virus
Not directly oncogenic, but is implicated in Burkitt lymphoma (lymphoma of b lymphocytes)
Hyperkalemia
Symptoms - decreased heart contractility Causes - excessive potassium in blood leading to depolarization of muscle cells. Due to trauma, kidney problems etc TREATMENT - 1.) Ca gluconate to hyperpolarize RMP 2.) insulin to pump K+ into cells 3.) dialysis to resolve problems longer term
Cataracts
Symptoms - high fluid pressure and lens glycosylation of eye. Blindness and vision loss. Causes - hyperglycemia (glucose fructose or galactose) causing sugars to utilize the polyol pathway which causes high concentrations of fructose and sorbitol in the eye –> increased osmotic pressure and non-enzymatic glycosylation of the lens
No ApoCA1 protein thus large increases in VLDL and LDL due to inability to bind LPL. Early cardiovascular problems
Tangier’s disease
Symptoms - RBC rupturing, jaundice, and splenomegaly. Cause - unusual cytoskeletal support system leading to RBC’s losing their biconcave shape.
Hereditary spheorcytosis
GSD III (cori disease)
Symptoms - fasting hypoglycemia, KETOACIDOSIS, hyperlipidemia, hepatomegaly with elevated AST/ALT, Causes - deficiency of 1,6 glucosisdase activity of debranching enzyme Treatment - frequent high carb meals
Symptoms - self injury (biting lips and fingers, elevated uric acid, mental retardation, dystonia, recurrent vomiting, often die in 30s due to renal failure Cause - rare x linked disorder, defeciency in hypoxanthine-guanine phoshporibosyltransferase (HGPRT) He’s Got Purine Recycline Trouble Treatment -allopurinol to decrease uric acid
Lesch-Nyhan Syndrome
Neurofibromatosis (NF1)
Symptoms - multiple benign fleshy tumors called neurofibromas in the skin; multiple flat, irregular pigmented skin lesions called cafe au lait spots; hamaratomas of the iris Cause - autosomal dominant disease with variable expressivity (differing diseased phenotypes with the same genotype) with full penetrance (all who have the mutation show disease)
Symptoms - plaques on hands and feet, corneal ulcers, mental retardation, elevate tyr Causes - rare autosomal recessive mutation in tyrosine aminotransferase Treatment - diet low in tyr
Tyrosemia II
Lesch-Nyhan Syndrome
Symptoms - self injury (biting lips and fingers, elevated uric acid, mental retardation, dystonia, recurrent vomiting, often die in 30s due to renal failure Cause - rare x linked disorder, defeciency in hypoxanthine-guanine phoshporibosyltransferase (HGPRT) He’s Got Purine Recycline Trouble Treatment -allopurinol to decrease uric acid
Scurvy
Symptoms - gingivival lesions, enlargement of costochondral joints, petichiae, slow wound healing, irritability/apathy, and anemia Cause -Vitamin C deficiency leading to collagen degredation Treatment - diet rich in fruits and vegetables
Tay Sachs Disease
Symptoms- mental retardation, blind, deaf, and spastic infants. Death by around 3 years of age Causes - autosomal recessive mutation of alpha subunit of hexosamidase enzyme which affects hexosamidase A leading to accumualtion of gangliosides –> lysosomal storage disease *Much more common in Ashkenzazi Jews
Beneign defeciency in fructokinase leads to false positives in diabetes urine testing
Essential fructosuria
Malignant Hyperthermia
Ryanidine becomes unbound in the presence of halothane or other anesthetics resulting in continuous calcium pumping. Burning of ATP for this gives off heat.
Ackee fruit ingestion causes MCAD like symptoms due to hypoglycin toxin, acute
Jamaican Vomiting Sickness
Gout
Symptoms - high uric acid, accumulation of uric acid crystals in distal joints –> very painful, exacerbated by the cold Causes - overactive xanthine oxidase? increased uric acid (GMP and AMP are degraded to xanthine Treatments - allopurinol blocks xanthine oxidase
Autoimmune attack of the Hemidesmosome leading to blistering in lamina lucida between epidermis and dermis
Bullous pemphigoid
Symptoms - decreased heart contractility Causes - excessive potassium in blood leading to depolarization of muscle cells. Due to trauma, kidney problems etc TREATMENT - 1.) Ca gluconate to hyperpolarize RMP 2.) insulin to pump K+ into cells 3.) dialysis to resolve problems longer term
Hyperkalemia
Symptoms - cheliosis and glossitis (lips and tongue let you taste FLAVor) also present as keratitis, seborrheic dermatitis, normocytic anemia Causes - lack of riboflavin (B2) a precursor to FMN and FAD and HIF deregulation causing upregulation of glycolysis and other anoxic genes. Treatment - a diet rich in milk, eggs, organ meats, legumes, and mushrooms
Riboflavin deficiency
Symptoms - scaly dermatitis, thining hair, alopecia Causes - Biotin deficiency due to avidin from egg whites which sequesters biotin rendering it inactive
Biotin deficiency
Pellegra
Symptoms - DDD Dementia, Dermatitis, and Diarrhea, also glossitis Causes - Niacin deficiency which is an essential precursor to NAD/NADP. Due to a diet that is only corn or alchoholics. Treatment- Diet rich in meat, whole grains, and fortified cereals
Achrondroplasia
Symptoms - short stature Causes - increased function due to a single amino acid change resulting in overactivation of firbroblast growth factor receptor (FGFR) *know this as example of gain of function mutation
Symptoms - infants -siezures ; adults - peripheral neuropathy Causes - inborn metabolism errors in two areas; antiquitin deficiency or pyridoxine oxidase deficiency Treatment - antiquitin deficiency can supplement either pyridoxine or pyridoxal or pyridoxamine pyridoxine oxidase deficiency which can only be treated with pyridoxal or pyridoxamine.
Pyridoxine deficiency (PLP)
Human T-cell leukemia virus type 1 (HTLV-1)
virus causes adult t cell leukemia/lymphoma via signaling pro-growth and survival and genomic instability. Doesn’t involve proto-oncogenes.
Symptoms - low but not absent T cells, chronic infections, FTT, neurologic symptoms Causes - defeciency in purine nucleoside phosphorylase (PNP) –> buildup of adenosine which is toxic especially to lymphocytes
Combined immunodeficiency (CID)
Long QT
Symptoms - hearth arrhthmia with a long QT segment Causes - likely potassium issues, but many possible causes
Symptoms - hyperlipidemia, premature CVD, xanthomas causes - mutations in LDL receptor Treatment - statins, diet, and anything that lowers cholesterol
Familial Hypercholestemia
Symptoms - Hyperammonaemia, Hyperglutaminia and elevated urotic acid decreased intermediates in urea cycle Causes - x linked recessive deficiency Treatments - liver transplant (especially neonates), citrulines, low nitrogen diet
Orinthine transcarbamoylase
Cystinuria
Symptoms - cysteine precipitates as kidney stones Causes - autosomal recessive inherited mutation in amino acid carrier for cysteine, defective transporters to take cysteine back out of the lumen of the kidney, precipitates in the duct,
Pyridoxine deficiency (PLP)
Symptoms - infants -siezures ; adults - peripheral neuropathy Causes - inborn metabolism errors in two areas; antiquitin deficiency or pyridoxine oxidase deficiency Treatment - antiquitin deficiency can supplement either pyridoxine or pyridoxal or pyridoxamine pyridoxine oxidase deficiency which can only be treated with pyridoxal or pyridoxamine.
Symptoms - SIDS, normal glucose tolerance, variable exercise intolerance, cardiac and muscle hypertrophy Causes - rare autosomal recessive defeciency in glycogen synthase
GSD0
GSD V (McArdle disease)
Symptoms - Late childhood onset of exercise intolerance –> myoglobinuria after exercise, increased creatine kinase, exaggerated increase in creatine kinase and ammonia after exercise Causes - Deficiency of muscle glycogen synthase Treatment - avoid exercise and try to build tolerance
Lactose intolerance
Primary lactase deficiency - gradual decline presenting in adolesence Secondary lactase deficiency - due to damage of brush border of intestinal enterocytes Congenital lactase deficiency - rare genetic condition resulting in complete lactase deficiency
Teratocarcinomas
Symptoms - benign or malignant growths of tissues such as hair, muscle, bits of teeth etc. Cause - uncontrolled growth of germ cells.
BRCA2 mutation
Symptoms - breast cancer Causes - Mutations in repair by homologous recombination.
I-cell disease
autosomal recessive lysosomal storage disease due to DEFECT IN PROTEIN TRAFFICKING
Paraneioplastic syndromes
symtom complexes in cancer-bearing individuals that cannot be explained by tumor itself.
Maple Syrup Urine Disease
Symptoms - hypoglycemia and ketoacidosis, one week old infants present with convulsions, vomitting, maple syrup odor in urine, elevated BCAAs in blood Causes - Inability to break down BCAA Treatment - acute - hydration and transfusion chronic - synthetic low BCAA, thiamidine in mild cases
Collagen metabolism disturbance leading to hyper-flexibility and reoccurrent joint dislocation
Ehlers/Danlos
non-neoplastic disorganized aggregate of mature tissues indigenous to the site of origin.
Hamartoma
Galactokinase deficiency
Symptoms - galactose accumulates, cataracts Causes - deficiency in galactokinase not allowing metabolism Treatment- eliminate lactose –> good prognosis
Hereditary spheorcytosis
Symptoms - RBC rupturing, jaundice, and splenomegaly. Cause - unusual cytoskeletal support system leading to RBC’s losing their biconcave shape.
Familial Autism
Symptoms - autism/siezure disorder Causes - hyperactive branch chain breakdown enzymes Treatment - High BCAA diet
Symptoms - breast cancer Causes - Mutations in repair by homologous recombination.
BRCA2 mutation
Hyperglobinemia
Too many plasma cells
Sandhoff disease
Symptoms - mental retardation, blind, deaf, spastic, death within a year or so Causes - congenital defect in Beta subunit of hexosamidase affects hexosamidase B and A–> accumulation of gangliosides and globosides in lysosomes
Cholera
Know AB toxin. Toxin binds B and A diffuses into the cell inhibiting the breakdown of cAMP which leads to an increase in cAMP and subsequently CFTR. Increased Cl- in the intestinal lumen - water follows - severe diarrhea
Tyrosemia II
Symptoms - plaques on hands and feet, corneal ulcers, mental retardation, elevate tyr Causes - rare autosomal recessive mutation in tyrosine aminotransferase Treatment - diet low in tyr
Symptoms - salt wasting, hypovolemia, fuel homeostasis problems, male sex hormones in females Causes - mutation in steroid hormone biosynthesis genses i.e. cyp21
Congenital Adrenal Hyperplasia
Symptoms- present in problems in high energy demand tissues i.e. CNS and muscle. Causes - mutation rate in mitochondria are 10x higher, maternally inherited, segregate randomly thus wide array of phenotypes and age progressive.
Mitochondrial disorders
Symptoms - increased serum fatty acyl carnitine, muscle pain, weakness, myoglobuinuria, (adult) FTT, fatal (infant/neonatal) Causes - Autosomal recessive disorder of CPT II enzyme which decreases lipid metabolism
CPT II deficiency
Symptoms - exercise intolerance, muscle cell break down, myoglobinuria, no increase in blood NH4, no AMPD1 in muscle biopsy Causes - deficient myoadenylate deaminase –> inability to replenish TCA intermediates
Myoadenylate Deaminase Defficiency
GSD I (von Gierke disease)
Symptoms: fasting hypoglycemia, LACTIC ACIDOSIS, Hepatomegaly, Hyperuricemia, Hyperlipidemia Causes - glucose-6-phosphatase defeciency in liver –> accumulation of glucose innability to leave the liver Treatment - frequent meals, avoid cornstarch
Symptoms - episodic hypoglycemia (when liver glycogen is depleted) Cause - no gluconeogensis treatment- eating often
Fructose 1,6 bisphosphatase deficiency
Diffuse large b cell lymphoma (DLBCL)
two classes: germinal center B cell DLBCL (good prognosis) and Activated B cell like DLBCL (poor prognosis)
treatments: monoclonal antibodies.
Adenocarcinomas
malignant epithelial neoplasms showing glandular differentiation
Symptoms - FTT, hepatomegaly, liver failure, FATAL Causes - 4,6 transferase deficiency (branching enzyme)
GSD IV
Symptoms - hemolytic anemia Cause- inability to reduce glutathione when oxidative stress is present resulting in free radical accumulation. common inborn error of metabolism (x-linked recessive) Treatment - avoid oxidative stress especially xenobiotics and fava beans (we know SMX causes this)
Glu-6-p DH deficiency
Beriberi
Symptoms - “I can’t, I can’t” confusion, malaise, peripheral neuropathy (dry) and cardiac problems (wet) Causes - Thiamine deficiency due to malnutrition, alcoholism, and monotonous diet (thiamine is a precursor to TPP) Treatment - Diet rich in meat, legumes, whole grains, and fortified cereals.
Sickle Cell Anemia
Symptoms - Sickled RBC’s leading to aggregation of RBC’s exacerbated by dehydration, altitude etc, increased risk of stroke, and hypoxia due to occlusion Causes - point mutation converting a glutamic acid to valine at position 6 in B chain of hemoglobin HbA- normal HbS -Sickle Celll HbC - Glu6Lys Treatment - acute management of stroke: blood transfusion (monthly - worry about iron overload) ; hydroxyurea which increases fetal hemoglobin (no Beta chain this is carcinogenic and low white cell count) ; on prophylactic anitibiotics due to low white cell count and splenectomy. Cholystectomy common due to high RBC turnover causing increase in bilirubin and gall stones. During crisis - ibuprofen, hydration, oxygen
Klinefelter’s Syndrome
1/1000 males, caused by extra copies of xxy
Cachexia
Symptoms- progressive loss of both body fat and lean muscled mass along with weakness and anorexia that is associated with cancer. Systemic inflammation.
Cause- cancer patients have increased metabolic rate despite reduced food consumption. Not caused by nutritional demands of the tumor.
****Unexplained weight loss can be a presenting symptom in cancer!!!!!
