MCM Diseases Flashcards
Niemann-Pick Disease
Cause: deficiency in activity of A-SMase.
A-SMase breaks down sphingomyelin.
Leads to hepatomegaly, splenomegaly, and hallmark cherry spot in the eye.
Erythroblastosis fetalis
Mother is Rh- and fetus is Rh+. Mom makes ABs against fetus’ RBCs.
Spur Cell Anemia
Elevated cholesterol in RBCs, causing rigidity. RBCs lyse as they pass through splenic capillaries, causing hemolytic anemia.
Cystic Fibrosis
Mutation in CFTR gene. Cl- cannot leave epithelium, causing an increase in NaCl. Water follows, causing thic secretions and increase RTIs.
Cystinuria
Defect in transport of Cysteine (and Arg, Lys, Orn). Results in cysteine stones in the kidney.
Hartnup Disease
Defect in transport of for nonpolar and uncharged AAs (think Trp and its derivatives). Leads to lack of muscle control, photodermatitis, photosensitivity.
Cardiotonic drugs and HF
Cardiotonics inhibit the Na/K pump and lead to an increase of Ca2+ inside the cell (think about why this would happen). Increases contraction.
Components of TEE (4)
BMR =/= RMR
Thermic affect of food (digestion)
Physical activity
Non-exercise induced thermogenesis
Vit B1
Thiamine
Coenzyme in many metabolic pathways (glcolysis, TCA, PPP non-ox phase)
Wernicke’s (ataxia), Korsakoff’s (psychosis), dry beriberi (muscle wasting), wet beriberi (HF).
Vit B2
Riboflavin
FAD/FMN
Corneal neovasularization, cheilosis, magenta colored tongue.
Vit B3
Niacin
NADH/NADPH (synthesized from W)
Hartnup disease can cause deficiency.
Manifests as Pellagra.
Vit B5
Pantothenic acid
CoA
Dermatitis, numbness, parasthesia, cramps, hypoglycemia.
Vit B6 (no manifestations)
Pyridoxine
ALT, AST
Vit B7
Biotin
Cofactor for carboxylation enzymes. (in GNG, FA synthesis)
Alopecia, rashes, bowel inflammation, muscle pain.
Vit B9
Folic acid
de novo pyrimidine synthesis.
Anemia, homocysteinemia.
Vit B12
Cobalamin
Coenzyme for homocysteine metyltransferase and methylmalonyl- CoA mutase.
Manifests as anemia, neuropathy, homocysteinemia.
Vit C
Ascorbate
Cofactor for colagen synthesis, norepi synthesis, Fe absorption.
Manifests as Scurvy
Vit A and deficiency origin
Retinol, retinoic acid, retinal.
Deficient from malabsorption, fat malabsorption and cirrhosis.
Maintains vision and epithelium.
Vit D (function, disease, symptoms)
Calcitriol.
GI (synthesize Ca2+), kidneys (reabsorption of Ca 2+), bone (bone resorption). All about Ca 2+!
Rickets.
Delayed growth, muscle pain/weakness, bowed legs.
Diabetes (I and II)
Type I: insulin deficiency due to loss of beta cells.
Type II: insulin resistance due to loss of beta cell function.
Tarui Disease
PFK-1 deficiency.
Mild but can cause muscle cramps and h. anemia.
F 1,6 BP deficiency
Similar to Tarui, but in GNG.
Can cause hypoglycemia, lactic acidosis.
Von Gierke Disease
Glucose 6-phosphatase deficiency.
Hypoglycemia, lactic acidosis, hepatomegaly (due to build up of glycogen).
Fanconi-Bickel syndrome
Mutation in GLUT 2. Unable to take in glu, gal, fru.
Failure to thrive, hepatomegaly, rickets.
Treat with Vit D.
GALT deficiency
Leads to accumulation of galactitol.
Can cause failure to thrive, liver failure, sepsis, bleeding.
Galactokinase deficiency
Leads to accumulation of gal and galactitol in blood and urine.
Can cause early cataracts.
GSD 0
Defective enzyme: glycogen synthase
Pathway affected: chain elongation
GSD II
Pompe Disease
Defective enzyme: acid maltase
Pathway affected: lysosomal glycogenolysis - cannot release glc.
GSD III
Cori Disease
Defective enzyme: debranching enzyme
Pathway affected: glc cleavage and release from branch point.
GSD IV
Andersen Disease
Defective enzyme: glucosyl 4:6 transferase
Pathway affected: chain branching
GSD V
McArdle Disease
Defective enzyme: muscle glycogen phosphorylase
Pathway affected: glc 1-P release
GSD VI
Hers Disease
Defective enzyme: liver glycogen phosphorylase
Pathway affected: glc 1-P release
2-oxoglutaric aciduria
d/o of TCA.
Causes developmental delay and severe neurological problems in infants (metabolic acidosis, microcephalopathy, mental retardation).
Fumarase deficiency
d/o of TCA
Causes severe neurological impairment. Fatal within 2 years. Also causes encephalopathy, dystonis, increased urinary output of fumarate, succinate, citrate and a-KG.
Succinyl-CoA synthetase (SCS) deficiency
Mutations in 2 of 3 subunits (SUCLA2 and SUCLG1). Predictable pattern of dytonia and deafness. Genetic testing can help diagnose.
Mitochondrial depletion syndrome
Severe hypotonia, progressive dystonia, muscular atrophy, and severe sensory impairment.
Luft’s Disease
Increased metabolic function with normal thyroid activity. Caused by uncoupled ox-phosp, high levels of cytochrome c and low levels of Q
Primary causes of mitochondrial diseases (2)
Defect in nuclear DNA encoding mitochondrial proteins.
Defect in mitochondrial DNA
Secondary causes of mitochondrial diseases
Ischemia, repefusion, CVD, renal failure, drugs, alcohol, smoking.
Clinical features of mitochondrial diseases
Nervous system, eyes, skeletal muscle, heart
Metabolic features of mitochondrial diseases (3)
Low energy production.
Increased free radical production.
Lactic acidosis.
MCAD deficiency
Impairs breakdown of MCFAs, leading to secnodary carnitine deficiency.
FA accumulates in liver, interferes with urea cycle and increases levels of ammonia.
Patients must depend on Glu for energy.
Homocystinuria
Caused by defective cystathione b-synthase or Vit B6 deficiency. Increases levels of homocysteine, but can be helped by Vit B6 supplementation.
Mostly affects eyes, skeleton, CNS and vascular system.
MSUD
Deficienct BCKD cannot breakdown L,I,V. Blood accumulates in brain and can cause problems with brain function and eventually mental retardation. Thiamine (VB1) supplements can elp in some mild cases.
PKU
Defect in PAH. Phe converted to phenyllactate and phenylacetone instead of Tyr.
Can disrupt NT transmission and brain function.
Albanism
Defect in tyrosinase.Cannot form melanin from Tyr.
Gout
Increase in uric acid which crystalizes in distal parts of the body. Treated with diet change, then allopurinol to block xanthine oxidase.
Lesch-Nyhan syndrome
Defect in HGPRT enzyme in purine salvage pathway.
Overproduction or uric acid, leading to gout. Commonly causes kidney stones, gout, ataxia, mental retardation and self mutilation.
Kwashiokor
Severe protein deficiency.
Edema, light skin, hair thinning, distended abdomen, anemia, fatty liver.
Marasmus
Protein and calorie deficiency.
Emaciated, chronic diarrhea, RTIs, stunted growth, intellectual disabilities, no energy. Weight is less than 62% expected.
Metabolic syndrome
One of: DM, impaired glc tolerance, impaired fasting glc, insulin resistance.
Two of: HTN, dyslipidemia, obesity, or microalbuminuria.
