Porfyrie
Inhoudsopgave
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1 verplicht aanvullend onderzoek
1.1 algemeen
- eerst indeling in drie grote groepen
- eerst meting totaal urine-porfirine, daarna subtyperen
1.2 PCT / HEP
- passende kliniek?
- generally presents in adulthood
- dermatose: chronic blistering photosensitivity, especially on the backs of the hands and other sun-exposed areas, which can lead to infection, scarring, hyper- and hypopigmentation
- neurovisceral attacks: no
- lab: elevations in serum transaminases, plasma and urine total porphyrins elevated
- characteristic pattern in urine, plasma, feces, zie tabel beneden, notabel:
- plasma peak fluorescence at 620 nm distinguishes PCT from variegate porphyria (VP)
- total fecal porphyrins in PCT may be normal
- erytrocytporfyrine anders
- moleculaire analyse UROD
- bij vermoeden familiaire vorm
- wens voor genetische counseling
- doel: verkorten patient/doctor delay waardoor minder kans op HCC, en verminderen onzekerheid
1.2.1 HEP
- HEP: more severe, usually in childhood, erytrocytporfyrine anders, mutation of both UROD alleles
1.2.2 specifiek PCT
- HCV, HIV
- ferritine en ijzerparameters
- moleculaire analyse UROD, HFE
- alcohol use, smoking, estrogen use, and hepatitis C virus (HCV) or human immunodeficiency virus (HIV), hemochromatosis (HFE) mutations
2 therapie
2.1 therapie PCT / HEP
- acquired susceptibility factors: alcohol use, smoking, estrogen use, and hepatitis C virus (HCV) or human immunodeficiency virus (HIV), hemochromatosis (HFE) mutations
2.1.1 PCT
- zon vermijden tot daling porfyrine
- medicatie die acute porfyrie uitlokken vermijden
- PCT 20% inherited (heterozygous) and 80% sporadic (not heterozygous)
- reduction of susceptibility factors (ook bij asymptomatisch dragerschap)
- indicatie therapie: active skin lesions
- ferritine >650 of twee aangedane HFE genen: phlebotomy als bij HH
- anders: low-dose hydroxychloroquine of flebotomie
- based on: other susceptibility factors, contraindications to either treatment, and other factors: cost, convenience, side effect profile
- contraindications to hydroxychloroquine: pregnancy, advanced liver disease, regular alcohol use, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and retinal disease
- hydroxychloroquine 100 mg twice weekly after ophthalmological clearance with measurement of porphyrin levels
- recurrences can be re-treated with hydroxychloroquine; however, long-term administration during remission is not advisable
- bij HCV: na remissie PCT pas therapie; snelle start momenteel experimenteel
2.1.2 HEP
- vermijden zonlicht
3 prognose
- bij PCT normaal behoudens effect van risico-factoren
4 tabellen
4.1 kenmerken per klinische groep
| Type of porphyria | Specific porphyria | Urine | Stool | Erythrocytes | Plasma |
|---|---|---|---|---|---|
| Acute neurovisceral | ADP | ALA, coproporphyrin III | * | Zinc protoporphyrin, Markedly decreased ALAD activity | ALA* |
| Acute neurovisceral | AIP | ALA, PBG, uroporphyrin, coproporphyrin | * | Decreased PBGD activity by approximately 50% (most cases)* | ALA, PBG* [approximately 620 nm]¶ |
| Acute neurovisceral, rarely cutaneous | HCP | ALA, PBG, coproporphyrin III | Coproporphyrin III | * | Δ [approximately 620 nm]¶ |
| Acute neurovisceral, commonly cutaneous | VP | ALA, PBG, coproporphyrin III | Coproporphyrin III, protoporphyrin | * | Porphyrin-peptide conjugate [approximately 626 to 628 nm]¶ |
| Cutaneous, blistering | PCT and HEP | Uroporphyrin, heptacarboxyl porphyrin | Heptacarboxyl porphyrin, isocoproporphyrins | Zinc protoporphyrin (markedly elevated in HEP, normal or mildly elevated in PCT) | Uroporphyrin, heptacarboxyl porphyrin [approximately 620 nm]¶ |
| Cutaneous, blistering | CEP | Uroporphyrin I; coproporphyrin I | Coproporphyrin I | Uroporphyrin I; coproporphyrin I | Uroporphyrin I, coproporphyrin I [approximately 620 nm]¶ |
| Cutaneous, nonblistering | EPP and XLP | ◊ | Protoporphyrin* | Metal-free protoporphyrin§ | Protoporphyrin |
*Porphyrin levels normal or slightly increased.- ¶ Fluorescence emission peak of diluted plasma at neutral pH.
- Δ Plasma porphyrins usually normal, but increased when blistering skin lesions develop.
- ◊ Urine porphyrins (especially coproporphyrin) increase only with hepatopathy.
- § Zinc protoporphyrin ≤5 percent of total in classic EPP, but 15 to 50% in variant form (XLP).
4.2 kenmerken per diagnose
| Disease | Tissue site | Clinical features | Enzyme affected | Inheritance | Urine | Plasma | Erythrocytes | Feces |
|---|---|---|---|---|---|---|---|---|
| ADP | Hepatic¶ | Acute | ALAD | Autosomal recessive | ALA, coproporphyrin III | Zinc protoporphyrin and low ALAD activity | ||
| AIP | Hepatic | Acute | PBGD | Autosomal dominant | ALA, PBG, uroporphyrin, coproporphyrin | Low PBGD activity | ||
| HCP | Hepatic | Acute and cutaneous | CPOX | Autosomal dominant | ALA, PBG, uroporphyrin, coproporphyrin III | Coproporphyrin III | ||
| VP | Hepatic | Acute and cutaneous | PPOX | Autosomal dominant | ALA, PBG, uroporphyrin, coproporphyrin III | Fluorescence peak at approximately 626 nm | Coproporphyrin III and protoporphyrin | |
| PCT | Hepatic | Cutaneous | UROD | Autosomal dominantΔ | Uroporphyrin and hepta-carboxyl-porphyrin | Uroporphyrin and hepta-carboxyl-porphyrin | Isocoproporphyrin | |
| HEP | Hepatic¶ | Cutaneous | UROD | Autosomal recessive | Uroporphyrin and hepta-carboxyl-porphyrin | Uroporphyrin and hepta-carboxyl-porphyrin | Zinc protoporphyrin and low UROD activity | Isocoproporphyrin |
| CEP | Erythropoietic | Cutaneous | UROS | Autosomal recessive | Uroporphyrin I and coproporphyrin I | Uroporphyrin I and coproporphyrin I | Uroporphyrin I and coproporphyrin I | Coproporphyrin I |
| EPP | Erythropoietic | Cutaneous | FECH | Autosomal recessive | Protoporphyrin, fluorescence peak at approximately 634 nm | Metal-free protoporphyrin | Protoporphyrin | |
| XLP | Erythropoietic | Cutaneous | ALAS2 | X-linked | Protoporphyrin | Metal-free and zinc protoporphyrin | Protoporphyrin |
-The table shows the classification based on tissue site (ie, hepatic or erythropoietic) and on clinical features (ie, acute or cutaneous). The affected enzymes, inheritance patterns, and biochemical findings are listed. Refer to UpToDate for details of initial testing for suspected porphyria and diagnostic evaluations for each specific porphyria.