Heme synthesis disorders

Question 1

Microcytic hypochromic anemia

Answer 1

• any decrease in the amount of heme/Hb
• causes in heme synthetic pathway include:
• Lead poisoning:
  
  • ALA Dehydrase
  • Ferrochelatase
• Vit B6 def.; Isozoniazide Rx for TB causes B6 def
• Iron def

Question 2

Acute Intermittent Porphyria

Answer 2

• hepatic porphyria
• Hydroxymethylbilane synthase (Porphobilinogen Deaminase) def
• Generally present in adult life
• Clinical Sx:
  
  • accumulation of ALA & PBG
  • GI Sx: cramping ab pain, nausea & vomiting.
  • Neuropsych sx
  • Peripheral neuropathy; motor neurons so check DTR
  • Pt not photo sensitive
• Dx.
  
  • increased urinary excretion of PBG & ALA
  • Urine nl in colour on voiding but turns dark on exposure to light as PBG gets converted to porphobin by light
• Rx:
  
  • symptomatic Rx: Hemin given IV helps by inhibiting ALA synthase; thereby decreasing production of PBG
  • Barbiturates should not be given to calm these Pt as they are inducers of CYP & activate ALA synthase

Question 3

Porphyria Cutanea Tarda

Answer 3

• Uroporphyrinogen Decarboxylase
• commonest porphyria
• can be inherited or acquired
• accumulation of Uroporphyrinogen III
• may be due to an inhibitor of enzyme synthesized in liver. Synthesis of inhibitor is greatly dependent on the amount of iron present in hepatocytes
• Clinical Sx:
  
  • chronic
  • blistering skin lesions commonest presentation
  • Werewolf: Hypertrichosis & hyperpigmentation
  • Photosensitivity
  • Urine dark red in colour voiding w/o exposure due to increased Uroporphyrin
  • Urinary PBG levels are generally nl
  • Aggravated by increased hepatic iron load
• Rx
  
  • symptomatic Rx
  • Phlebotomies/blood letting to decrease hepatic iron content

Question 4

Congenital Erythropoietic Porphyria

Answer 4

• Uroporphyrinogen III Synthase def. in erythrocyte precursor cells
• Autosome RECESSIVE (exception) & rare
• Clinical Sx;
  
  • early in childhood
  • reddish discolouration of skin
  • blistering skin lesions on exposure to sunlight
  • pink staining of diapers in neonates
  • Photosensitivity
  • Reddish discolouration of teeth
  • Hemolytic anemia as accumulation of uroporphyrins in RBC increases their fragility
• Dx:
  
  • urine dark red in colour due presence of Uroporphyrin
  • Increased urinary conc. of Uroporphyrin I
  • nl ALA & PBG levels
  • Increased conc. of Uroporphyrins in erythrocytes (highly indicative of the disease)
• Rx:
  
  • Avoidance of sun & use of protective sunscreens
  • Vit. E & C for protection against damage by free radicals
  • attempts to reduce Erythropoiesis by repeated transfusions have resulted in some improvement but have their own set of complications
  • Bone marrow transplant