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!!!!!
Symptoms - progressive renal, cv, and cerebrovascular failure from glucose, galactose globosides Causes - x linked lysomal disorder of alpha- galactocerebrocidase Treatment - enzyme replacement therapy (agalsidase)
Fabry disease
Osteogenesis imperfecta
Brittle bone disease due to diseased collagen metabolism
autosomal recessive lysosomal storage disease due to DEFECT IN PROTEIN TRAFFICKING
I-cell disease
Symptoms - progressive dementia Causes - KNOW THIS AS AN EXAMPLE OF MUTATION LEADING TO NEURODEGENERATIVE DEFECT.
Alzheimer’s Disease
Common skin cancer usually caused by thiamine-thiamine dimer formation. This can be fixed by NER.
Melanoma
hyperhomocysteinemia
Symptoms - plaques, cardiovascular problems, neurological problems Causes - B12 deficiency, methinione synthase mutation/deficiency, or vitamin B6 (pyridoxal phosphate) defeciency (needed for many transaminations)
CPT II deficiency
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
Downs Syndrome
Symptoms - mild to moderate mental retardation, Test values - first trimester increase in BHCG and low PAPP-A. Second trimester = low AFP and high HCG and inhibin A. Causes - Trisomy 21. Certain miRNA’s are expressed at higher rates resulting in abnormal gene expression. Trisomy 21 is lethal in 75% of fetuses. Large increase with maternal (and paternal) age. 1/15 in women over 45 and an 8 FOLD INCREASE RISK OF RECURRENCE!!! Treatment - parental counseling. Large percentage of couples or women choose abortion.
Symptoms - developmental mental retardation Causes - AS is silenced on paternal gene, so if mutation occurs on maternal gene disease is expressed due to lack of active AS gene. If paternal imprinting problems AS gene overactivity causes disease as well. NEED ONE ACTIVE GENE.
Angelman Syndrome
Symptoms - hearth arrhthmia with a long QT segment Causes - likely potassium issues, but many possible causes
Long QT
Alzheimer’s Disease
Symptoms - progressive dementia Causes - KNOW THIS AS AN EXAMPLE OF MUTATION LEADING TO NEURODEGENERATIVE DEFECT.
Pernicious anemia
Symptoms - Megaloblastic anemia plus neuropathy, blood and urine positive for methylmalonic acid (MMA) Causes: Neuropathy is due to S-adenosyl methionine’s (needs cobalamin to make from homocysteine) importance in neurotransmitter production cobalamin (vitamin B12) defeciency this can be due to: dietary, loss of function of intrinsic factor, transcobalamin II, or cubillin. Often seen in vegans!
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
Gout
Symptoms - confusion and and mental status changes, abnormal eye movements, and ataxia 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.
Wernicke encephalopathy
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
Sandhoff disease
Symptoms - edema, irritability Causes - Negative nitrogen balance –> due to anorexia, famine, severe trauma
Kwarshiorkor
Symptoms- high LDL and subsequent CVD Causes - mutation in LDL receptor leading to increase in blood LDL and artherosclerosis. KNOW THIS AS AN EXAMPLE OF DEFECT IN RECEPTOR DISEASE.
Hypercholeserolemia
Ehlers/Danlos
Collagen metabolism disturbance leading to hyper-flexibility and reoccurrent joint dislocation
Symptoms - progressive muscle weakness and delath of myocytes. Test female for elevated levels of creatine kinase to check for carrier. Cause - x linked mutation in dystrophin protein which leads to losing of structural integrity of cell membrane.
Duchenne’s Muscular Dystrophy
Benzopyrene carcinogencity
When benzopyrene is oxidized in cells it become carcinogenic due to it’s causing of G to A transition mutations which often silence p53.
Jamaican Vomiting Sickness
Ackee fruit ingestion causes MCAD like symptoms due to hypoglycin toxin, acute
HHH (Hyperammonaemia, Hyperorintaemia, and Homocitrulinaemia ) syndrome
Symptoms - HHH Caused - orinthine/citruline antiporter is defective
Alcaptonuria
Symptoms - homogentisate in urine, dark urine, asymptomatic until middle age, arthritis, back pain, renal calculi Causes - rare autosomal recessive deficiency in homogentisate oxidase Treatment - manage pain, manage kidney stones
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
Phenylketonuria (PKU)
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
Sickle Cell Anemia
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
Scurvy
Symptoms - High rates of colorectal and endometrial cancer that runs in family Cause - Defect in DNA mismatch repair
Lynch syndrome
adenoma
benign epithelial neoplasms showing glandular differentiation
Urea cycle disorders
Higher up the disorder the higher orotic acid Treatments are Arginine (regenerate orinthine and pee out arginosuccinate), benzoid acid, or phenylbutyrate (make amino acids excretable in urine) , liver transplant, low protein diet, N-carbamoyl acid (treats NAG synthase defeciency)
Megaloblastic Anemia
Results from dietary folate defeciency. Blood cells rapidly divide –> requires deoxynucleotieds (which the cells can’t make enough of due to defeciency)–> cells grow large because they can’t divide until they replicate their genomes. Most apparent in bone marrow, also blood.
Combined immunodeficiency (CID)
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
Medium Chain Acyl CoA Dehydrogenase (MCAD) deficiency
Symptoms - Accumulation of medium chain acyl coa’s, nonketotic hypoglycemia Causes - inborn error in acyl CoA DH
Symptoms - HHH Caused - orinthine/citruline antiporter is defective
HHH (Hyperammonaemia, Hyperorintaemia, and Homocitrulinaemia ) syndrome
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
Maple Syrup Urine Disease
Symptoms - accumulation of glucocerebroside in brain, liver, bone marrow, and spleen Causes - autosomal recessive defect in Beta glucosidase –> lysosomal storage disease Treatment - Infusion of recombinant Beta glucosidase (imiglucerase)
Gaucher disease
Fructose 1,6 bisphosphatase deficiency
Symptoms - episodic hypoglycemia (when liver glycogen is depleted) Cause - no gluconeogensis treatment- eating often
Hypercholeserolemia
Symptoms- high LDL and subsequent CVD Causes - mutation in LDL receptor leading to increase in blood LDL and artherosclerosis. KNOW THIS AS AN EXAMPLE OF DEFECT IN RECEPTOR DISEASE.
Ataxia-telangiectasia
Symptoms - neurodegeneration, susceptibility to cancer, and genome instability Causes - defects in ATM protein which is important for signaling DNA damage.
Tangier’s disease
No ApoCA1 protein thus large increases in VLDL and LDL due to inability to bind LPL. Early cardiovascular problems
Symptoms - characterized by amnesia and confabulation. present in 80% patients with wernicke encephalopathy 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.
Karsokoff psychosis
Biotin deficiency
Symptoms - scaly dermatitis, thining hair, alopecia Causes - Biotin deficiency due to avidin from egg whites which sequesters biotin rendering it inactive
Orinthine transcarbamoylase
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
H pylori
Implicated in gastric adenocarcinoma and gastric lymphomas
Multiple myeloma
Tumor of the plasma cells
Karsokoff psychosis
Symptoms - characterized by amnesia and confabulation. present in 80% patients with wernicke encephalopathy 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.
Epimerase deficiency
Symptoms - jaundice, hepatomegaly, hypoglycemia, lethargy , FTT (same as classic galactosemia) Cause - epimerase deficiency treatment - galactose RESTRICTED diet (need some for glycosylation etc)
Symptoms - galactose accumulates, cataracts Causes - deficiency in galactokinase not allowing metabolism Treatment- eliminate lactose –> good prognosis
Galactokinase deficiency
Symptoms - neurodegeneration, susceptibility to cancer, and genome instability Causes - defects in ATM protein which is important for signaling DNA damage.
Ataxia-telangiectasia
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
Cholera
Bullous pemphigoid
Autoimmune attack of the Hemidesmosome leading to blistering in lamina lucida between epidermis and dermis
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
GSD V (McArdle disease)
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 GENE.
Prader-Willi Syndrome (PWS)
Congenital Adrenal Hyperplasia
Symptoms - salt wasting, hypovolemia, fuel homeostasis problems, male sex hormones in females Causes - mutation in steroid hormone biosynthesis genses i.e. cyp21
Too many plasma cells
Hyperglobinemia
Myoadenylate Deaminase Defficiency
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
GSD IV
Symptoms - FTT, hepatomegaly, liver failure, FATAL Causes - 4,6 transferase deficiency (branching enzyme)
Brittle bone disease due to diseased collagen metabolism
Osteogenesis imperfecta
Symptoms - mild to moderate mental retardation, Test values - first trimester increase in BHCG and low PAPP-A. Second trimester = low AFP and high HCG and inhibin A. Causes - Trisomy 21. Certain miRNA’s are expressed at higher rates resulting in abnormal gene expression. Trisomy 21 is lethal in 75% of fetuses. Large increase with maternal (and paternal) age. 1/15 in women over 45 and an 8 FOLD INCREASE RISK OF RECURRENCE!!! Treatment - parental counseling. Large percentage of couples or women choose abortion.
Downs Syndrome
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)
Neurofibromatosis (NF1)
Tyrosinemia I
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
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
Pellegra
Medulloblastoma
Advanced cancers result in multiple copies of chromosomes often with chromosome fusions. (crazy looking FISH)
Tumor of the plasma cells
Multiple myeloma
Symptoms - homogentisate in urine, dark urine, asymptomatic until middle age, arthritis, back pain, renal calculi Causes - rare autosomal recessive deficiency in homogentisate oxidase Treatment - manage pain, manage kidney stones
Alcaptonuria
alpha - AT
symptoms - higher incidence in emphysema and lung cancer Causes - Know as a defect in co-factor metabolism. mutation in protein involved in the breakdown of various proteases that can damage lung tissue.
Aldolase B deficiency
Symptoms - recurrent hypoglycemic episodes, FTT, hepatic failure Causes - traps fructose as fructose one phosphate –> phosphate/energy sink due Treatments - avoid fructose like the plague
Symptoms - jaundice, hepatomegaly, hypoglycemia, lethargy , FTT (same as classic galactosemia) Cause - epimerase deficiency treatment - galactose RESTRICTED diet (need some for glycosylation etc)
Epimerase deficiency
No cilia –> sterility, upper respiratory problems, and situs inversus
Kartagener’s syndrome
Associated with folate deficiency during/before pregnancy. Test high AFP in second trimester of pregnancy. Neural tube defect
Spina Bifida
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
Severe combined immunodeficiency (SCID)
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
Achrondroplasia
Kwarshiorkor
Symptoms - edema, irritability Causes - Negative nitrogen balance –> due to anorexia, famine, severe trauma
Duchenne’s Muscular Dystrophy
Symptoms - progressive muscle weakness and delath of myocytes. Test female for elevated levels of creatine kinase to check for carrier. Cause - x linked mutation in dystrophin protein which leads to losing of structural integrity of cell membrane.
Kartagener’s syndrome
No cilia –> sterility, upper respiratory problems, and situs inversus
Higher up the disorder the higher orotic acid Treatments are Arginine (regenerate orinthine and pee out arginosuccinate), benzoid acid, or phenylbutyrate (make amino acids excretable in urine) , liver transplant, low protein diet, N-carbamoyl acid (treats NAG synthase defeciency)
Urea cycle disorders
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
GSD III (cori disease)
Symptoms - Hyperammonaemia , Hyperglutaminia, normal orotic Acid
CPS I deficiency
symptoms - higher incidence in emphysema and lung cancer Causes - Know as a defect in co-factor metabolism. mutation in protein involved in the breakdown of various proteases that can damage lung tissue.
alpha - AT
Symptoms - Accumulation of medium chain acyl coa’s, nonketotic hypoglycemia Causes - inborn error in acyl CoA DH
Medium Chain Acyl CoA Dehydrogenase (MCAD) deficiency
Symptoms - Megaloblastic anemia plus neuropathy, blood and urine positive for methylmalonic acid (MMA) Causes: Neuropathy is due to S-adenosyl methionine’s (needs cobalamin to make from homocysteine) importance in neurotransmitter production cobalamin (vitamin B12) defeciency this can be due to: dietary, loss of function of intrinsic factor, transcobalamin II, or cubillin. Often seen in vegans!
Pernicious anemia
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.
Beriberi
Angelman Syndrome
Symptoms - developmental mental retardation Causes - AS is silenced on paternal gene, so if mutation occurs on maternal gene disease is expressed due to lack of active AS gene. If paternal imprinting problems AS gene overactivity causes disease as well. NEED ONE ACTIVE UBE3A GENE.
Glu-6-p DH deficiency
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)
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
Lactose intolerance
Advanced cancers result in multiple copies of chromosomes often with chromosome fusions. (crazy looking FISH)
Medulloblastoma
Symptoms - plaques, cardiovascular problems, neurological problems Causes - B12 deficiency, methinione synthase mutation/deficiency, or vitamin B6 (pyridoxal phosphate) defeciency (needed for many transaminations)
hyperhomocysteinemia
Symptoms - susceptible to skin cancers, susceptible to other cancers Causes - autosomal recessive disorder that results in defective DNA repair especially nucleotide excision repair
Xeroderma Pigmentosum
Human papillomavirus
Symptoms- Can lead to cervical cancer.
Cause - inhibits host apoptosis, inactivates tumor suppressors, and combats senescence.
Symptoms - premature aging, cancer at several sites, genome instability Cause - Enzyme defects in 3’ exonuclease function and DNA helicase
Werner’s Syndrome
Results from dietary folate defeciency. Blood cells rapidly divide –> requires deoxynucleotieds (which the cells can’t make enough of due to defeciency)–> cells grow large because they can’t divide until they replicate their genomes. Most apparent in bone marrow, also blood.
Megaloblastic Anemia
Rous Sarcoma Virus
Symptoms - mutated form or our gene is an oncogene that leads to continuous signaling and cancer and errors in DNA replication, Cell proliferation, Differentiation Causes - Mutated viral SRC gene
Spina Bifida
Associated with folate deficiency during/before pregnancy. Test high AFP in second trimester of pregnancy. Neural tube defect
Galactose 1 phosphate uridyl transferase deficiency (classic galactosemia)
Symptoms - jaundice, hepatomegaly, hypoglycemia, lethargy, FTT Cause - deficient enzyme treatmetn - eliminate gal from the diet –> poor prognosis
CPS I deficiency
Symptoms - Hyperammonaemia , Hyperglutaminia, normal orotic Acid
Fabry disease
Symptoms - progressive renal, cv, and cerebrovascular failure from glucose, galactose globosides Causes - x linked lysomal disorder of alpha- galactocerebrocidase Treatment - enzyme replacement therapy (agalsidase)
GSD0
Symptoms - SIDS, normal glucose tolerance, variable exercise intolerance, cardiac and muscle hypertrophy Causes - rare autosomal recessive defeciency in glycogen synthase
Familial Adenomatous Polyposis (FAP)
Symptoms - people who inherit the mutation develop thousands of adenomas by the second decade
Cause - inherited form of Colorectal cancer where families carry a mutant copy of APC. Apc controls levels of catenin which in turn inhibits the activation of myc and others. Loss of this function leads to uncontrolled proliferation.
Treatment - requiring colonic resection, but many die later of GI cancers.
Gaucher disease
Symptoms - accumulation of glucocerebroside in brain, liver, bone marrow, and spleen Causes - autosomal recessive defect in Beta glucosidase –> lysosomal storage disease Treatment - Infusion of recombinant Beta glucosidase (imiglucerase)
Symptoms - mutated form or our gene is an oncogene that leads to continuous signaling and cancer and errors in DNA replication, Cell proliferation, Differentiation Causes - Mutated viral SRC gene
Rous Sarcoma Virus
When benzopyrene is oxidized in cells it become carcinogenic due to it’s causing of G to A transition mutations which often silence p53.
Benzopyrene carcinogencity
Symptoms - jaundice, hepatomegaly, hypoglycemia, lethargy, FTT Cause - deficient enzyme treatmetn - eliminate gal from the diet –> poor prognosis
Galactose 1 phosphate uridyl transferase deficiency (classic galactosemia)
Symptoms - recurrent hypoglycemic episodes, FTT, hepatic failure Causes - traps fructose as fructose one phosphate –> phosphate/energy sink due Treatments - avoid fructose like the plague
Aldolase B deficiency
Melanoma
Common skin cancer usually caused by thiamine-thiamine dimer formation. This can be fixed by NER.
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
Tay Sachs 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
GSD I (von Gierke disease)
Chronic myelogenous leukemia
Symptoms - Chronic form of blood cancer in which bone marrow makes too many WBCs
Causes- BCR-ABL translocation between chromosome 9 and 22. results in an overactive tyrosine kinase.
Treatment - Gleebec which blocks BCR-ABL binding that leads to CML.
Wernicke encephalopathy
Symptoms - confusion and and mental status changes, abnormal eye movements, and ataxia 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.
Lynch syndrome
Symptoms - High rates of colorectal and endometrial cancer that runs in family Cause - Defect in DNA mismatch repair
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,
Cystinuria
Mitochondrial disorders
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.
Familial Hypercholestemia
Symptoms - hyperlipidemia, premature CVD, xanthomas causes - mutations in LDL receptor Treatment - statins, diet, and anything that lowers cholesterol
Riboflavin deficiency
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
Xeroderma Pigmentosum
Symptoms - susceptible to skin cancers, susceptible to other cancers Causes - autosomal recessive disorder that results in defective DNA repair especially nucleotide excision repair
Marfan’s syndrome
Firbrillin gene defect causing misfuncitonal elastic fibers which can lead to catastrophic rupture of aorta.
