Chemical Pathology - Porphyrias Flashcards
What are porphyrias?
7 disorders caused by deficiency in enzymes, involved in haem biosynthesis, leading to build-up of toxic haem precursors
What are the three factors used to differentiate between the acute porphyrias?
- Skin lesions: Present in HCP + VP only
- Urine + faeces for porphyrins: Raised in HCP + VP only
- Urine PBG: raised in all three
How is acute intermittent porphyria diagnosed?
- Increased urinary porphobilinogen (PBG)
- Increased aminolevulinic acid
What are some precipitating factors of acute intermittent porphyria?
- ALA synthase inducers: steroids, ethanol, barbiturates
- Stress: infection, surgery
- Reduced calory intake + endocrine factors: premenstrual
What is the management of acute intermittent porphyria?
- Avoid precipitating factors
- Adequate nutrition + analgesia
- Mx of underlying infection/illness
- IV carbohydrate
- IC haem arginate
What is the mode of inheritance of acute intermittent porphyria?
Autosomal dominant
What is the cause of acute intermittent porphyria?
HMB (hydroxymethylbilane) synthase deficiency
If a patient is hyponatraemic with acute intermittent porphyria, what condition is this indicative of?
SIADH
If a patient has a change in their urine colour + abdominal pain what condition is this indicative of?
Acute intermittent porphyria
Why are there no cutaneous manifestations of Acute intermittent porphyria?
There is an absence of porphyrinogens
What are some symptoms of acute intermittent porphyria?
Neurovisceral only (P’s):
- Painful abdomen
- Peripheral neuropathy
- Psychosis
- Port urine
- Seizures
- Muscle weakness
- Constipation
- Urinary incontinence
What is the mode of inheritance of hereditary coproporphyria (HCP)?
Autosomal dominant
What is the mode of inheritance of variegate porphyria (VP)?
Autosomal dominant
How does hereditary coproporphyria (HCP) manifest?
Neurovisceral:
- 4P’s (painful abdo, peripheral neuropathy, psychosis + port urine)
Skin Sx:
- Skin lesion fragility (skin lesions on back of hands, blister under the sun)
How does variegate porphyria (VP) manifest?
Neurovisceral:
- 4P’s (painful abdo, peripheral neuropathy, psychosis + port urine)
Skin Sx:
- Skin lesion fragility (skin lesions on back of hands, blister under the sun)
What is the investigation of choice for hereditary coproporphyria (HCP)?
Stool sample for coproporphyrinogen III
What is the investigation of choice for variegate porphyria (VP)?
Stool sample for coproporphyrinogen III
Which porphyrias manifest with skin lesions only (e.g. blistering skin lesion + pigmentation)?
Cutaneous Non-acute Porphyrias
- Porphyria Cutanea Tarda (PCT)
- Erythropoeitic Protoporphyria (EPP)
- Congenital erythropoeitic porphyria (CEP)
What are the commonest + second commonest porphyrias?
Commonest: Porphyria Cutanea Tarda
2nd Commonest: Acute Intermittent Porphyria
What is the cause of porphyria cutanea tarda?
Uroporphyrinogen decarboxylase deficiency
How does porphyria cutanea tarda present?
- Photosensitivity
- Facial hyperpigmentation
- Hypertrichosis
- Blistering
- Milia
- Scarring
- Exacerbated by alcohol
What investigations/results are seen in porphyria cutanea tarda?
- Increased urinary uroporphyrins
- Increased urinary coproporphyrins (pink red fluorescence with Wood’s lamp)
- Increased ferritin
- Abnormal LFTs
What is the management of porphyria cutanea tarda?
- Avoid sun + precipitants (alcohol, hepatitis C, HIV)
- Chloroquine
What is the clinical manifestation of erythropoeitic protoporphyria and which population is it most commonly seen in?
- Found in children
- Cutaenous erythema without blisters/bullae
Why can’t you test urine in erythropoeitic protoporphyria?
protoporphyrin is lipophilic
What investigations are used to diagnose erythropoeitic protoporphyria?
RBC protoporphyrin levels
What is the clinical manifestation of congenital erythropoeitic porphyria?
cutaenous erythema with blistering
