Disorders of heme biosynthesis

Disorders of heme biosynthesis

Q. 1 A girl on sulphonamides developed abdominal pain and presented to emergency with seizure. What is the probable diagnosis?

 A

Acute intermittent porphyria

 B

Congenital erythropoietic porphyria

 C

Infectious mononucleosis

 D

Kawasaki disease

Q. 1

A girl on sulphonamides developed abdominal pain and presented to emergency with seizure. What is the probable diagnosis?

 A

Acute intermittent porphyria

 B

Congenital erythropoietic porphyria

 C

Infectious mononucleosis

 D

Kawasaki disease

Ans. A

Explanation:

Abdominal pain is the most common symptom in Acute intermittent porphyria and is usually steady and poorly localized but may be cramping. Seizures can be due to neurologic effects or to hyponatremia.
Treatment of seizures is difficult because most anti seizure drugs can exacerbate AIP (clonazepam may be safer than phenytoin or barbiturates).
 
The drugs which precipitate attacks of acute intermittent porphyria are microsomal enzyme inducers.
They are metabolized by p450 enzyme. In response to these drugs the synthesis of cytochrome p450 proteins increases, leading to an enhanced consumption of heme, a component of p450 proteins.
This in turn causes a decrease in the concentration of heme in the liver.
Since the patient is deficient in enzymes synthesizing porphyrins it cannot makeup for the increase in demand of porphyrins.
This leads to increased accumulation of porphyrin precursors precipitating attacks of porphyria.
 
Some important drugs causing acute intermittent porphyria :-
  • Barbiturate
  • Chloramphenicol
  • Sulfonamides
  • Thiopental Na
  • Oral contraceptives
  • Phenylbutazone
  • Rifampicin
 
Ref: Desnick R.J., Balwani M. (2012). Chapter 358. The Porphyrias. In D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds), Harrison’s Principles of Internal Medicine, 18e.

Q. 2

A 27-year-old woman goes to an emergency room with severe abdominal pain. She had previously experienced similar episodes of pain that lasted several hours to a few days, but this episode is the most severe. She has also been experiencing nausea, vomiting, and constipation. The physician is left with the impression that she is agitated and somewhat confused, and an accurate history is difficult to elucidate. The patient is sent for emergency laparotomy, but no pathology is noted at surgery. Following the unrevealing surgery, an older surgeon comments that he had once seen a similar case that was actually due to porphyria.The porphyrias are biochemical abnormalities in which of the following pathways?

 A

Glycogen degradation

 B

Heme synthesis

 C

Lipoprotein degradation

 D

Nucleotide degradation

Q. 2

A 27-year-old woman goes to an emergency room with severe abdominal pain. She had previously experienced similar episodes of pain that lasted several hours to a few days, but this episode is the most severe. She has also been experiencing nausea, vomiting, and constipation. The physician is left with the impression that she is agitated and somewhat confused, and an accurate history is difficult to elucidate. The patient is sent for emergency laparotomy, but no pathology is noted at surgery. Following the unrevealing surgery, an older surgeon comments that he had once seen a similar case that was actually due to porphyria.The porphyrias are biochemical abnormalities in which of the following pathways?

 A

Glycogen degradation

 B

Heme synthesis

 C

Lipoprotein degradation

 D

Nucleotide degradation

Ans. B

Explanation:

The porphyrias are a group of rare, related diseases that have in common a block in the heme synthesis pathway. The block is usually partial rather than complete, and thus many of these patients have only intermittent symptoms. Most cases of porphyria present with either a neurovisceral pattern (including both psychiatric symptoms and abdominal pain) or with photosensitive skin lesions. These two patterns are associated with different forms of porphyria.
Must know:

  • Associate abnormalities of glycogen degradation (with the glycogen storage diseases, such as Von Gierke disease, Pompe disease, and Forbes disease.
  • Associate abnormalities of lipoprotein degradation with some forms of hyperlipoproteinemia (notably Type I).
  • Associate abnormalities of nucleotide degradation with Gout and Lesch-Nyhan syndrome.
Ref: Murray R.K. (2011). Chapter 31. Porphyrins & Bile Pigments. In D.A. Bender, K.M. Botham, P.A. Weil, P.J. Kennelly, R.K. Murray, V.W. Rodwell (Eds), Harper’s Illustrated Biochemistry, 29e.

Q. 3 The enzyme deficient in erythropoietic porphyria is:

 A

PBG deaminase

 B

Uroporphyrin II cosynthetase

 C

Coprophyrin

 D

Ferrochelatase

Q. 3

The enzyme deficient in erythropoietic porphyria is:

 A

PBG deaminase

 B

Uroporphyrin II cosynthetase

 C

Coprophyrin

 D

Ferrochelatase

Ans. D

Explanation:

 

–  Erythropoietic protoporphyria is due to deficiency of enzyme ferrochelataseQ.

–  All porphyrias are autosomal dominant (AD) except congenital erythropoietic porphyria (autosomal recessive, AR), ALA dehydratase (porphobilinogen) deficiency (AR) and X-linked protoporphyria (X-linked).

Quiz In Between


Q. 4 Which of the following porphyrias is not inherited as an Autosomal Dominant disorder-

 A

Acute Intermittent Porphyria

 B

Congenital Erythropoietic Porphyria

 C

Porphyria Cutanea Tarda

 D

Hereditary Coproporphyria

Q. 4

Which of the following porphyrias is not inherited as an Autosomal Dominant disorder-

 A

Acute Intermittent Porphyria

 B

Congenital Erythropoietic Porphyria

 C

Porphyria Cutanea Tarda

 D

Hereditary Coproporphyria

Ans. B

Explanation:

Ans. is ‘b’ i.e., Congenital erythropoietic porphyria

Inheritance of Porphyrias

Autosomal dominant                                       Autosomal Recessive                                   X-linked

o Acute intermittent porphyria (AIP)            o ALA dehydratase deficiency                   o X-linked protoporphyria

o Porphyria cutanea Tarda (PCT)                 o Congenital erythropoietic porphyria

o Hereditary coproporphyria (HCP)             o Erythropoietic protoporphyria o Variegate porphyria (VP)


Q. 5 In porphyrias, which of the following enzyme defects does not lead to photosensitivity

 A

Uroporphyrinogen synthase

 B

Uroporphyrinogen decarboxylase

 C

Protoporphyrinogen oxidase

 D

Coproporphyrinogen oxidase

Q. 5

In porphyrias, which of the following enzyme defects does not lead to photosensitivity

 A

Uroporphyrinogen synthase

 B

Uroporphyrinogen decarboxylase

 C

Protoporphyrinogen oxidase

 D

Coproporphyrinogen oxidase

Ans. A

Explanation:

Ans.a. Uroporphyrinogen synthase
(Ref Harper 29/e p3l2-314, 27/e p277)
In porphyrias, uroporphyrinogen synthase enqlme defects lead to Acute Intemittent Porphyria, which shows purely
ne urological manifestation witho ut photosensitivity.


Q. 6

Skin is not involved in ‑

 A

Erythropoietic porphyria

 B

Porphyria cutanea torda

 C

Acute intermittent porphyria

 D

Hereditary coproporphyria

Q. 6

Skin is not involved in ‑

 A

Erythropoietic porphyria

 B

Porphyria cutanea torda

 C

Acute intermittent porphyria

 D

Hereditary coproporphyria

Ans. C

Explanation:

Ans. is ‘c’ i.e., Acute intermittent porphyria

Type of Porphyria  Neuropsychiatric symptoms Skin symptoms/Phototoxicity 

Hepatic porphyrias

Acute intermittent porphyri a

5-ALA dehydratase deficiency

Hereditary coproporphyria

Variegate porphyria

Porphyria cutanea tarda

 
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 Erythropoietic porphyrias

Erythropoietic protoporphyria

Congenital erythropoietic porphyria

X-linked sideroblastic anemia

 
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Quiz In Between



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