Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.
A Case Report: X-linked
Dominant Protoporphyria
Matthew Seager
ACS iSSC
Objectives
Introduction
Porphyrias
Classification
Erythropoetic and X-linked dominant
protoporphyrias (EPP & XLDPP)
W...
Introduction - Porphyrias
Heterogeneous group of inherited metabolic disorders of
the haem biosynthesis pathway
Due to a...
Porphyrias - Classification
Adapted from Thadani et al 2000
Neurovisceral (“Acute porphyrias”):
•Acute attacks of
Neuro – ...
EPP & XLDPP
Adapted from Puy et al 2010
EPP – Painful photosensitivity
& liver dysfunction
XLDPP – Painful photosensitivit...
Why is this topic important?
Rare (EPP 1:75,000-200,000) but great impact on life
The initial study (Whatley et al 2008)...
Case report - XLDPP
18 year old ♀
PC – “Burning” photosensitivity
HPC:
 Lifelong. Occurs “within minutes” of sun expos...
Case report - XLDPP
FH:
Case report - XLDPP
Investigation Result Reference Comment
Bloods
Erythrocyte total porphyrin
(μmol/L)
60.6 0.4-1.7  sugg...
Case report - XLDPP
Management plan:
 Advised RE: sun avoidance
 Reflectant sunscreen vs visible light
 Narrow band UV...
XLDPP (& EPP) – Future hope
Afamelanotide (α-MSH analog):
Preliminary results - RCT 100 EPP patients promising
Bone mar...
Conclusions
XLDPP and EPP are photocutaneous porphyrias
Pathophysiological similarities disorders
present/managed almost...
Learning points
Disability & disadvantage:
 Great impact of “benign” pathology
Consultation & procedural skills:
 Witn...
Thanks for listening.
References
 Thadani H, Deacon A, Peters T. Diagnosis and management of
porphyria. BMJ 2000; 320(7250):1647-51.
 Puy H, G...
Upcoming SlideShare
Loading in …5
×

A Case Report: X-linked Dominant Protoporphyria

437 views

Published on

  • Be the first to comment

A Case Report: X-linked Dominant Protoporphyria

  1. 1. A Case Report: X-linked Dominant Protoporphyria Matthew Seager ACS iSSC
  2. 2. Objectives Introduction Porphyrias Classification Erythropoetic and X-linked dominant protoporphyrias (EPP & XLDPP) Why is this topic important? Case report – XLDPP Conclusions and learning points
  3. 3. Introduction - Porphyrias Heterogeneous group of inherited metabolic disorders of the haem biosynthesis pathway Due to abnormalities of the haem synthesis enzymes and accumulation of haem precursors & porphyrins Majority of haem synthesis occurs in haematopoietic marrow cells (also liver parenchymal cells) Toxic effects of porphyrins/precursors symptoms
  4. 4. Porphyrias - Classification Adapted from Thadani et al 2000 Neurovisceral (“Acute porphyrias”): •Acute attacks of Neuro – neuropathy, seizures, psychiatric Visceral – colic, abdominal pain, vomitingPhotocutaneous: •Painful bullous eruptions and/or scarring – PCT/CEP •Acute, painful photosensitivity without external signs – EPPMixed: Neurological & photocutaneous features
  5. 5. EPP & XLDPP Adapted from Puy et al 2010 EPP – Painful photosensitivity & liver dysfunction XLDPP – Painful photosensitivity & liver dysfunction
  6. 6. Why is this topic important? Rare (EPP 1:75,000-200,000) but great impact on life The initial study (Whatley et al 2008) found:  17% clinically overt liver disease c.f. 2% EPP  Close to 100% penetrance c.f EPP and other porphyrias  X-linked Revise X-linked disease & importance of biochem tests!! Implications for genetic counselling
  7. 7. Case report - XLDPP 18 year old ♀ PC – “Burning” photosensitivity HPC:  Lifelong. Occurs “within minutes” of sun exposure  No rash, erythema or swelling  Skin feels and appears normal in between episodes  Worse during summer months  Sunscreen – partial protection. Windows – none! PMH & DH - NAD EPP??
  8. 8. Case report - XLDPP FH:
  9. 9. Case report - XLDPP Investigation Result Reference Comment Bloods Erythrocyte total porphyrin (μmol/L) 60.6 0.4-1.7  suggests XLDPP/EPP Erythrocyte porphyrin screen Increased zinc & free PP IX N/A Suggests XLDPP Fluorescence emission spectroscopy (nm) Peak 633 630-634 in XLDPP/EPP Suggests XLDPP/EPP LFT Within normal ranges Suggests lack of liver pathology Faecal Total porphyrin (nmol/g dry weight) 459 10-200  suggests XLDPP Urine Porphyrin:creatinine ratio (nmol/mmol) 16 <40 Normal in XLDPP/EPP Genetic ALAS2 sequencing c.1706_1709 delAGTG N/A Recognised GoF XLDPP deletion
  10. 10. Case report - XLDPP Management plan:  Advised RE: sun avoidance  Reflectant sunscreen vs visible light  Narrow band UVB 3-4/week for summer 2012  Hepatology referral to establish monitoring Adapted from Timonen 2009
  11. 11. XLDPP (& EPP) – Future hope Afamelanotide (α-MSH analog): Preliminary results - RCT 100 EPP patients promising Bone marrow transplantation Harms et al 2009
  12. 12. Conclusions XLDPP and EPP are photocutaneous porphyrias Pathophysiological similarities disorders present/managed almost identically Lack of evidence for definitive management and current regimens fairly unsatisfactory Further research: treatment and prognosis
  13. 13. Learning points Disability & disadvantage:  Great impact of “benign” pathology Consultation & procedural skills:  Witnessed genetic counselling of family Evidence based medicine: Looked at evidence first hand
  14. 14. Thanks for listening.
  15. 15. References  Thadani H, Deacon A, Peters T. Diagnosis and management of porphyria. BMJ 2000; 320(7250):1647-51.  Puy H, Gouya L, Deybach JC. Porphyrias. Lancet 2010; 375(9718):924-37.  Whatley SD, Ducamp S, Gouya L, et al C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload. Am J Hum Genet 2008; 83(3):408-14.  Timonen K. Cutaneous porphyrias. Clinical and histopathological study. Academic Dissertation 2009. Department of Medicine Division of Dermatology and Allergology University of Helsinki, Finland  Harms J, Lautenschlager S, Minder CE, Minder EI. An alpha- melanocyte-stimulating hormone analogue in erythropoietic protoporphyria. N Engl J Med 2009; 360(3):306-7.

×