Porphyrias

Question 1

Porphyria cutanea tarda usually presents during the first and second decades of life

Answer 1

False third to fourth , usually not before puberty

Question 2

Acquired type 1 PCT represents 75% of cases, presenting in middle age

Answer 2

True

Question 3

Type II is familial UROD gene mutation accounting for 25%

Answer 3

True

Question 4

Risk factors for PCT

Answer 4

Alcohol
UROD deficiency
Hepatocellular ca
Dialysis in renal failure 
Iron overload H63D/C282Y
Hep B, Hep C
Male
Age >50
Hereditary haemochromatosis
OCP and exogenous oestrogens in females
Exogenous agents such as halogenated hydrocarbons

Question 5

Biochemical findings of PCT

Answer 5

Urine - uroporphyrin III
Faeces- Isocoporphyrin
Peak plasma fluorimetry 615-620nm

Question 6

Natural course of PCT

Answer 6

Blisters first remit 2-3 mo
Fragility takes 6-9 mo
Porphyrins take 12 mo to normalise
Hypertrichosis, sclerodermoid changes take years

Question 7

Aims of PCT treatment and targets

Answer 7

Induce mild Fe deficiency to reduce triggering haem synthesis
Aim of Hb 110-120
Fe <25
These can take 13 mo to achieve

Question 8

Features of congenital ERYTHROPOETIC porphyria

Answer 8

Presents with hydrops details, through to severe disease starting in infancy, but mild forms can present later in life

• first sign might be noting brown discolouration of amniotic fluid at onset of labour or pink/brown/violet porphyrins staining (red orange under Wood lamp)
• severe photosensitivity begins in infancy
• = blisters develop on minimal sun exposure
• exposed skin is fragile
• erythrodontia may be evident

Question 9

CEP biochemical findings

Answer 9

Urine - uroporphyrin I
Faeces - coproporphyrin I
Red cell - zinc and free protoporphyrin , uroporphyrin I, coproporphyrin I

Question 10

Extracutaneous features of CEP

Answer 10

Eyes- keratoconjunctivitis, cataracts, scarring alopecia eyelashes and eyebrows, corneal ulcers
Bones and teeth - teeth almost always stained brain , decr bone density are seen with pathological fractures
Haemolytic anaemia - due to marrow hyperplasia

Question 11

Erythropoetic porphyria inheritance

Answer 11

Newly classified AR - previously AD with incomplete penetrance

Question 12

EPP develop significant blisters in the first few years of life

Answer 12

False - oedema and pain

Question 13

Late onset of EPP is common

Answer 13

False - rare

Question 14

EPP 5% liver failure

Answer 14

True

Question 15

Hereditary coprophyria develop acute attacks without blisters

Answer 15

False, do get blisters

Question 16

HC Is autosomal dominant

Answer 16

True

Question 17

Deficiency in HC is ferrochelotase

Answer 17

False, coproporphyrinogen oxidase . Ferrochelotase is deficient in EPP

Question 18

HC has incr uro and coproporphyrin concentrations in urine and incr coproporphyrin in faces

Answer 18

True

Question 19

Variegate porphyria is autosomal recessive

Answer 19

False, dominant

Question 20

Risk of offspring developing VP is 50%

Answer 20

True as it is autosomal dominant

Question 21

Protophyrinogen oxidase is the deficiency in VP

Answer 21

True

Question 22

VP usually presents in infancy or childhood

Answer 22

False - adolescence or young adulthood

Question 23

VP indistinguishable from PCT

Answer 23

True

Question 24

VP biochemical findings

Answer 24

Urine coprophyrinoge, faecal coprophyrinogen , plasma fluorimetry is diagnostic with peak at 626nm

Question 25

Symptoms of an acute porphyria attack

Answer 25

GI - colicky abdo pain, nausea , vomiting, hyponatraemia Neurologic - seizures, psychosis, coma, paraesthesias, motor neuropathy, anxiety, muscle and back pain Cardiopulmonary - tachycardia, HTN, respiratory paralysis

Question 26

Management of acute attack

Answer 26

Key is early diagnosis Avoid attack inducing drugs Supportive Tx —> analgesia, usual tx safe ie. aspirin, morphine, ondansetron, 300mg CHO, B blockers for tachycardia and HTN, fluid balance and rehydration, correct hyponatraemia

Question 27

What can trigger an acute porphyria attack

Answer 27

``` P450 drugs (SHOEBAGS) Hormones Stress Fasting - need to advise carry sweets Surgery Infection ``` ``` DRUGS: Sulfur Hormones OCP Epileptics Barbiturates Antimalarials and amphetamines Griseofulvin Sedatives ```

Question 28

Pseudoporphyria drugs

Answer 28

``` NAT CL NSAIDs Tetracyclines Lasix Amiodarone Ciprofloxacin ```