2 - Clinical Correlation

• Aminoacidopathies are a class of inherited errors of metabolism where there is an absence of enzyme inhibiting the body's ability to metabolize certain amino acids
• Abnormalities can exist in the activity of a specific enzyme in the metabolic pathway or in the membrane transport system for amino acids
• These conditions cause severe medical complications due to the buildup of toxic amino acids and/or by-products of amino acid metabolism in the blood
• Phenylketonuria (PKU):

  • Caused by the absence of phenylalanine hydroxylase (PAH) enzyme
  • Leads to the accumulation of phenylalanine, inhibiting tyrosinase and impairing melanin formation
  • Symptoms include musty/earthy odor, mental retardation, failure to walk or talk, hypopigmentation, seizures, and tremors
• Maple-syrup urine disease (MSUD):

  • Caused by the absence of branched-chain alpha-ketoacid dehydrogenase
  • Blocks the normal metabolism of leucine, isoleucine, and valine
  • Symptoms include a maple syrup/burnt sugar odor of urine, breath, and skin
• Alkaptonuria:

  • Caused by the absence of homogentisate oxidase in tyrosine metabolism
  • Leads to homogentisate accumulation, giving urine a black color
  • Symptoms include alkapton deposition in connective tissues, bones, and organs, leading to ochronosis
• Collagenopathies involve defects in collagen fiber synthesis, resulting in the inability of collagen to form fibers properly and provide tissues with the needed tensile strength
• Scurvy:

  • Caused by vitamin C deficiency, critical in synthesizing collagen
  • Symptoms include bleeding gums, loose teeth, anemia, rough skin, and increased susceptibility to infections
• Marfan syndrome:

  • Connective tissue disorder affecting the skeleton, eyes, and cardiovascular system
  • Mutations in fibrillin-1 protein contribute to abnormal elastic tissue formation
  • Symptoms include malformed elastic fibers, blurred vision, weakening of the aorta, and disproportionately long limbs
• Ehlers-Danlos syndrome (EDS):

  • Characterized by hyperelasticity and hypermobility of joints
  • Inheritable defects in collagen metabolism lead to fragile skin and loose joints
  • Symptoms include lethal vascular problems, hematoma, and joint issues
• Osteogenesis imperfecta (brittle bone syndrome):

  • Causes bones that easily bend and fracture
  • Two types: tarda and congenital, with symptoms like retarded wound healing, spine deformities, and humped-back appearance
• Emphysema:

  • Lung disorder where alveolar walls disintegrate, leading to large air spaces and loss of elasticity
  • Typically caused by exposure to cigarette smoke and affects breathing
• Hemoglobinopathies are genetic disorders caused by abnormal hemoglobin molecules or insufficient quantities of normal hemoglobin
• Sickle-cell anemia:

  • Genetic disorder caused by a single nucleotide alteration in the beta-globin gene
  • Symptoms include anemia, joint pain, breathlessness, rapid heart rate, and abdominal pain
• Thalassemias:

  • Hereditary hemolytic disorders affecting the synthesis of globin chains of hemoglobin
  • Symptoms include fatigue, weakness, pale skin, slow growth, and abdominal swelling
• Carboxyhemoglobinemia (COHb):

  • Caused by exposure to carbon monoxide, leading to the formation of carboxyhemoglobin
  • Symptoms include headache, nausea, breathlessness, vomiting, and irritability
• Protein misfolding:

  • Alzheimer's disease is associated with amyloid deposits affecting cognitive function
  • Prion diseases involve misfolded proteins in the brain, leading to neurodegenerative disorders like Creutzfeldt-Jakob disease