Disorders of heme biosynthesis

Disorders of heme biosynthesis


Disorders  of heme  biosynthesis

  • porphyrias are a group of inborn errors  (or occasionally acquired) defects of heme biosynthesis.
  • This results in in the accumulation and increased excre-tion of porphyrins or porphyrin precursors.
  • The mutations that cause the porphyrias are heterogenous.
  • Each porphyria results in the accumulation of a unique pattern of intermediates caused by the deficiency of an enzyme in the heme synthetic pathway.
  • “Porphyria” refers to the purple color caused by pigment-like porphyrins in the urine of some patients with defects in heme synthesis.

Clinical manifestations:

  • The porphyrias are classified as erythropoietic or hepatic, depending on the enzyme deficiency in bone marrow or in the liver.
  • Most of the porphyrias are inherited autosomal dominant `EXCEPT
  1. ALAD enzyme Deficiency ADP
  2. Gongenital Erythropoeitic Porphyria CEp
  3. Erythropoetic Protoporphyria EPP
  4. X Linked Protoporphyria XLp
  • Accumulation of ALA and PBG causes Neuropsychiatric  and accumulation of porphyrin causes Photosensitivity.

Erythropoietic porphyrias

  • usually present with cutaneous photosensitivity. Most common Porphyria in children is Erythropoietic protoporphyria (Epp).
  • This disease is caused by to a deficiency in ferrochelatase. Protoporphyrin accumulates in erythrocytes, bone marrow, and plasma.•Patients are photosensitive. 

PORPHYRIA CUTANEA TARDA:

  • This disease is caused by a deficiency in uroporphyrinogen decarboxylase. Uroporphyrin accumulates in the urine.
  • It is the most common porphyria. Patients are photosensitive.
  • Uroporphyrinogen-I synthase (also called PBG dearninase or HMB synthase) causes Acute intermittent Porphyria
  • Uroporphyrtnogen  III  Synthase causes Congenital  erythropoietic.
  • Ferrochelatase (Heme synthase) causes Protoporphyria.

VARIEGATE PORPHYRIA

  • An acute disease caused by a deficiency in protoporphyrinogen oxidase.
  • Protoporphyrinogen IX and other intermediates prior to the block accumulate in the urine.
  • Patients are photosensitive.

HEREDITARY COPROPORPHYRIA:

  • An acute disease caused by a deficiency in coproporphyrinogen oxidase.Coproporphyrinogen III and other intermediates prior to the block accumulate in the urine.
  • Patients are photosensitive.

ACUTE INTERMITTENT PORPHYRIA:

  • An acute disease caused by a deficiency in hydroxymethylbilane synthase1.Porphobilinogen and δ-amino-levulinic acid accumulate in the urine. 
  • Urine darkens on exposure to light and air. Patients are NOT photosensitive.
  • Porphyrias leading to accumulation of ALA and porphobilinogen, such as acute intermittent por phyria, cause abdominal pain and neuro psychiatric disturbances.
  • In the liver, heme normally functions as a repressor of the gene for ALAS1. Therefore, the absence of this end product results in an increase in the synthesis of ALA synthase1(derepression).

Exam Important

Erythropoietic porphyrias

  • usually present with cutaneous photosensitivity. Most common Porphyria in children is Erythropoietic protoporphyria (Epp).
  • This disease is caused by to a deficiency in ferrochelatase. Protoporphyrin accumulates in erythrocytes, bone marrow, and plasma.•Patients are photosensitive. 

PORPHYRIA CUTANEA TARDA:

  • This disease is caused by a deficiency in uroporphyrinogen decarboxylase. Uroporphyrin accumulates in the urine.common porphyria. Patients are photosensitive.
  • Uroporphyrinogen-I synthase (also called PBG dearninase or HMB synthase) causes Acute intermittent Porphyria
  • Uroporphyrtnogen  III  Synthase causes Congenital  erythropoietic.
  • Ferrochelatase (Heme synthase) causes Protoporphyria.

VARIEGATE PORPHYRIA:

  • An acute disease caused by a deficiency in protoporphyrinogen oxidase.Protoporphyrinogen IX and other intermediates prior to the block accumulate in the urine.Patients are photosensitive.

ACUTE INTERMITTENT PORPHYRIA:

  • An acute disease caused by a deficiency in hydroxymethylbilane synthase1.Porphobilinogen and δ-amino-levulinic acid accumulate in the urine. Urine darkens on exposure to light and air. Patients are NOT photosensitive.                                        
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