FA Flashcards
Absent HGPRT –> increased de novo purine synthesis -> Increased uric acid production
Lesch-Nyhan syndrome
Mutation at splice site or promoter sequences –>retained intron in mRNA
β-thalassemia
Failure of mismatch repair during the S phase –> microsatellite instability
Lynch Syndrome
In N-acetylglucosaminyl-1-phosphotransferase defect, the Golgi doesn’t attach mannose-6-phosphate to proteins, so cellular debris isn’t sent to lysosomes for breakdown, causing the accumulation of debris there.
I-cell Disease
Type 1 collagen defect due to inability to form triple helices; mutation in
COL1A1 and COL1A2 genes
Osteogenesis imperfecta
Defective ATP7A protein can impair copper absorption and transport. This can reduce lysyl oxidase activity, which can reduce collagen cross-linking.
Menkes disease
FBN1 mutation, which occurs on chromosome 15, results in defective fibrillin. Normally, fibrillin creates a sheath around elastin.
Marfan syndrome
Uniparental disomy or imprinting leading to silencing of maternal gene.
Disease expressed when paternal allele deleted or mutated. Signs and symptoms includes: Hyperphagia, obesity, intellectual disability, hypogonadism, hypotonia
Prada-Willi Syndrome
Silenced paternal gene leading to mutation, lack of expression, or deletion of
UBE3A on maternal chromosome 15. Signs and Symptoms: Hand-flapping, Ataxia, severe Intellectual disability, inappropriate Laughter, Seisures -HAILS of Angel
Angelman Syndrome
The gene ΔF508 has a deletion mutation in the autosomal recessive CFTR gene on chromosome 7. This mutation leads to an impaired ATP-gated chloride channel that affects secretion of Cl− in the lungs and GI tract and reabsorption in sweat glands.
Cystic Fibrosis
Dystrophin gene frameshift mutations cause a loss of the anchoring protein to the ECM. The loss of anchoring protein (dystrophin) results in myonecrosis.
*X-linked recessive disorder
* Frameshift deletion or Nonsense Mutation
* Deleted Dystrophin
*weakness begins in pelvic girdle
* PSeudohypertrophy of CALF Muscles due to Fibrofatty replacement of Muscles
DILATED cardiomyopathy is common cause of Death
*Increased CK and Aldokase; Genetic Testing confirms diagnosis
Duchenne muscular dystrophy
The CTG trinucleotide repeat expansion in the DMPK gene leads to abnormal expression of myotonin protein kinase, which causes myotonia. Onset is 20-30 years.
*Autosomal Dominant
*Difficulty releasing Handshake
*muscle wasting
*cataracts
*Testicular atropy
*Toupee (early balding in males)
*Arrythmias
Myotonic Dystrophy
CGG trinucleotide repeat in the FMR1 gene leads to hypermethylation and, consequently, decreased expression.
*Full Mutation
* Macroorchididism (enlarged testes)
*Long faces with large jaw, large everted ears, MVP, hypermobile joints, Self mutilation is common and it is the most common inherited cause of intellectual disability - Down syndrome is the most common genetic cause of intellectual disability
Fragile X syndrome
Decreased differentiation of epithelial cells into specialized tissue this can lead to squamous metaplasia
- Night blindness
-Dry scaly skin (xerosis cutis)
-dry eyes (xerophthalmia)
-Bitot spot (conjunctival squammous metaplasia - Keratin debris, foamy appearance conjunctivia)
*ISOTRETINOIN is teratogenic
Vitamin A deficiency
Thiamine deficiency impairs glucose breakdown, which leads to ATP depletion, which is worsened by glucose infusion
Symptoms:
-Confusion
-Opthalmoplegia
-Nystagmus
-Ataxia
Dx: Made by increased RBC tranketolase activity following B1 administration
Wernicke Encephalopathy
Functions and disorders of Vitamin B1 (Thiamine Deficiency) Be APT
In thiamine Pyrophosphate (TPP), a co factor for several dehydrogenase enzyme reaction
- Branched -Chain Ketoacide dehydrogenase
-Alpha Ketodehydrogenase (TCA cycle)
-Pyruvate Dehydrogenase (Links glycolysis to TCA cycle)
-Transketolase (HMP shunt)
Disorders
-Wernicke Encephalopathy
-Korsaoff Syndrome (Amnestic disorder due to chronic alcohol overuse; presents with confabulation, personality changes, memory loss (permanent
- Wernicke-Korsakoff syndrome (Damage to media dorsal nucleus of thalamus, mammilary bodies. Presentation is a combo of wernicke encephalopathy and Korskoff syndrome
-Dry Beri-Beri (Polyneuropathy, symmetric muscle wasting
-Wet Beri Beri (High-output cardiac failure due to systemic vasodilation)
Tryptophan is diverted towards serotonin synthesis by tumor leading to B3
deficiency
(B3 aka Naicin is derived from tryptophan)
Pellegra in Malignant Carcinoid Syndrome
Protein malnutrition may lead to decreased oncotic pressure, which can lead to edema. Protein malnutrition can also result in decreased apolipoprotein synthesis, which can cause fatty liver disease.
Kwashiorkor
NADH/NAD+ Ratio can be increased in the liver due Ethanol metabolism which can lead to?
-Lactic acidosis ( Increase in pyruvate conversion to lactate)
- fasting hypoglycemia (Decreased gluconeogenesis due to increased conversion of OAA to Malate)
-hepatic steatosis in alcoholism ( Increase the conversion of DHAP to gycerol-3-P to synthesize triglycerides
-Ketoacidosis ( Diversion of acetyl-COA into ketogenesis rather than TCA cycle)
A competitive inhibitor of alcohol dehydrogenase; a preferred antidote for overdoses of Methanol or Ethylene glycol
FOMEPIZOLE
FOME - for overdose of Methanol or ethylene glycol
ETHANOL can also be used as a competitive inhibitor of alcohol dehydrogenase to treat Methanol or Ethylene glycol poisoning
Blocks acetaladehyde dehydrogenase causing increase in Acetaldehyde which increases hangover symptoms and discouraging drinking
DISULFIRAM
Increases permeability of mitochondrial membrane leads to a decreased proton [H+] gradient and an increase in O2 consumption, which causes uncoupling.
Aspirin-induced Hyperthermia
What is the pathophysiology of aldolase B deficiency?
Aldolase B deficiency, also known as Hereditary Fructose Intolerance, results in the accumulation of fructose-1-phosphate, which causes reduced availability of phosphate, and eventually the inhibition of glycogenolysis and gluconeogenesis.
