Clinical Correlation

• Aminoacidopathies:

  • Class of inherited errors of metabolism with enzyme defects inhibiting the body's ability to metabolize certain amino acids
  • Abnormalities in enzyme activity or membrane transport system for amino acids
  • Buildup of toxic amino acids and by-products in the blood
• Phenylketonuria (PKU):

  • Absence of phenylalanine hydroxylase enzyme
  • Characteristic musty odor, mental retardation, failure to walk or talk, seizures
  • Insufficient synthesis of serotonin due to competition with phenylalanine
  • Accumulation of phenylalanine inhibits tyrosinase and impairs melanin formation
• Maple-Syrup Urine Disease (MSUD):

  • Absence or reduced activity of branched-chain α-ketoacid dehydrogenase enzyme
  • Maple syrup or burnt sugar odor in urine, breath, and skin
  • Accumulation of branched-chain amino acids and ketoacids in blood, urine, and cerebrospinal fluid
• Alkaptonuria (Black Urine Disease):

  • Deficient homogentisate oxidase in tyrosine metabolism
  • Urine resembles coke in color
  • Alkapton deposition in connective tissue, bones, and organs causing ochronosis
  • Arthritis due to pigment alkapton deposition in joints
• Collagenopathies:

  • Defects in collagen fiber synthesis leading to genetic diseases
  • Scurvy:
  • Deficiency of ascorbic acid resulting in sore gums, loose teeth, anemia
  • Impaired collagen hydroxylation due to lack of prolyl and lysyl hydroxylase enzymes
• Marfan syndrome:

  • Connective tissue disorder with mutations in fibrillin-1 protein
  • Malformed or weakened elastic fibers in bones, eyes, and arteries
  • Disproportionately long arms, legs, fingers, and toes
• Ehlers-Danlos syndrome (EDS):

  • Generalized connective tissue disorders from collagen defects
  • Fragile, stretchy skin and loose joints due to collagen type III mutations
• Osteogenesis imperfecta:

  • Inherited disorders with easily bending and fracturing bones
  • Type I and Type II OI with different clinical presentations
• Elastinopathies:

  • Diseases from mutations in elastin gene affecting elastic fibers
  • Emphysema:
  • Alveolar wall disintegration due to neutrophil elastase activity
  • Shortness of breath, coughing, wheezing, chest tightness
• Hemoglobinopathies:

  • Genetic disorders from abnormal hemoglobin molecule production
  • Sickle-Cell Anemia:
  • Genetic blood disorder causing anemia, jaundice, joint pain
  • Substitution of valine for glutamic acid in hemoglobin A
• Thalassemias:

  • Hereditary hemolytic disorders from globin chain synthesis impairment
  • Alpha-Thalassemia and Beta-Thalassemia with different clinical features
• Carboxyhemoglobin (COHb):

  • Complex formed when hemoglobin exposed to carbon monoxide
  • Symptoms of headache, nausea, breathlessness, vomiting from CO toxicity
• Protein Misfolding:

  • Misfolded proteins tagged and degraded within the cell
  • Accumulation of misfolded proteins can lead to diseases
• Alzheimer's Disease:

  • Amyloid aggregation leading to memory loss and cognitive impairment
  • Abnormal fibrous deposits in organs and tissues
• Prion Disease:

  • Neurodegenerative disorders from misfolded prion proteins in the brain
  • Alteration in prion protein structure leading to insoluble aggregates
• Creutzfeldt-Jakob Disease:

  • Prion disease causing irreversible damage to nerve cells
  • Symptoms of dementia, muscle jerking, severe mental deterioration