Diseases Flashcards
Disorders of Amino Acid Metabolism: Phenylketonuria
-Most prevalent disorder caused by inborn errors of amino acid metabolism
Cause of Phenylketonuria
Mutations in the Phenylalanine Hydroxylase (PAH) gene
-Loss of PAH activity: increase in phenylalanine in blood and brain: leads to brain damage
Phenylketonuria presentation
Developmental delay low IQ level Autism Hypopigmentation Musty odor urine
Urine Odors Attributed to IEMs
Phenylketonuria: Musty, Mousy
Tyrosinemia: Musty, Cabbage like
Maple Syrup Urine Disease: Sweet, maple syrup
Isovaleric Acidemia: Sweaty feet
Multiple Carboxylase Deficiency: Cat Urine
Disorders of Fatty Acid Oxidation
F.A oxidation: process of mobilizing stored fat to meet increased energy demands
-interruption of any portion of this process will result in significant reductions in energy production
Medium Chain Acyl CoA dehydrogenase deficiency (MCAD)
- Episodic illness usually occurs first between 3 months to 2 years
- Usually follows fasting for >12 hours or with intercurrent infectious disease
Manifestations of MCAD
- Hyperketotic Hyperglycemia, Reyes like illness
- Acute Episode: vomiting, lethargy, or (potentially) seizures, leads to coma
Purpose of the Urea cycle?
Dispose of Nitrogen waste and biosynthesis of arginine
Omithine Transcarbamylase (OTC) deficiency
- X linked
- due to an error in the second reaction of ammonia detoxification
OTC: effects
- Affected males, early severe neonatal encephalopathy (rapid intervention needed to prevent morbidity and mortality)
- Increase NH3, Normal plasma glucose, Alkalosis, Normal plasma lactate, normal urine acids
Lysosomal Storage Disorders
- Defective lysosomal acid hydrolysis of endogenous macromolecules
- Accumulation of glycoproteins, glycolipids or glycosoamioglycans within lysosomes in various tissues (degenerative course)
Tay Sachs Disease
- AR disorder; overall prevalence 1:300,000
- Prevalent in Ashkenazi Jew and French Canadians
- Decrease in Hex A enzyme activity leads to increase in GM2 gangliosides, results in mental and motor retardation
Tay Sachs Features and Result
- Loss of Hearing, “Startled” response, Cherry Red macula
- Age 2: vegetative state, leads to death
Von Gierke Disease (GSD type 1)
- Cause: defective liver glucose 6 phosphatase activity
- Mutation: gene coding for the liver glucose 6 phosphatase; transport proteins of the glucose 6 phosphatase system
Von Gierke Disease Presentation
Initial symptoms from hypoglycemia: tremor, irritability, hyperventilation, apnea, convulsions, paleness, sweating, cerebral edema, coma, death
Von Gierke Disease key clinical symptoms
-Hyperlipidemia, hyperuricemia, osteoporosism lactic acidosis, ketosis
-With aging: Poor growth, short stature
(recurrent infections, neutropenia, inflammatory bowel disease, fever, diarrhea, perioral and anal ulcers
Disorders of Carbohydrate Metabolism
- A heterogenous group of disorders caused by inability to metabolize specific sugars, abherrent glycogen/glucose synthesis
- manifests with hypoglycemia, hepatosplenomegaly, lactic acidosis or ketosis
Glycogen Storage Disease
- Characterized by abnormal inherited glycogen metabolism in the liver, muscle, and brain
- leads to build up of glycogen in tissues
Klinefelter Syndrome
- A disorder in males, 47 XXY karyotype
- increased frequency of extragonadal germ cell tumors, DVT, PE, mitral valve prolapse, varicose veins, venous ulcers
Klinefelter Syndrome manifestations
Thin build Disproportionately long arms and legs Lower IQ than sibs Tall stature Poor Muscle tone Gyanaecomastia Small testicles/infertility Reduced 2nd sexual characteristics Predisposed to female like diseases due to extra X chromosome
Down Syndrome (trisomy 21) mutation
Whole chromosome aneuploidy (trisomy 21)
Down Syndrome MOA
- Long Duration in meiosis 1 in older moms
- Meiosis 1 begins at 3rd month of fetal (mom’s) life
- Meiosis 1 is paused in females and completed in puberty in meiosis to complete increase frozen stage of chromosomes
- increased chance of anaphase lag (aneuploid)
Down Syndrome Clinical Features
Flat face, small nose, epicanthal folds, Brushfield spots, Shirt 5th finger, Wide gap between 1st and 2nd toe, small mouth, bigger tongue, atrial septal defect, increased chance of getting leukemia, sudden spots on iris, lower IQ
Down Syndrome risks
Congenital Heart malformations
Alzheimer’s disease
Low muscle tone
vision and hearing problems
