124: The Porphyrias Flashcards
1
Q
What are the two main classifications of porphyrias based on the accumulation of heme precursors?
A
Porphyrias are classified as either hepatic or erythropoietic based on whether heme precursors first accumulate in the liver or bone marrow.
2
Q
What distinguishes cutaneous porphyrias from acute porphyrias?
A
Cutaneous porphyrias are characterized by overproduction and accumulation of photosensitizing porphyrins, leading to chronic blistering and scarring on sun-exposed skin. In contrast, acute porphyrias are marked by neurologic symptoms and elevated levels of porphyrin precursors, such as d-aminolevulinic acid (ALA) and porphobilinogen (PBG).
3
Q
What is the role of the enzyme ALAS in the heme synthesis pathway?
A
ALAS (Aminolevulinic Acid Synthase) is the first enzyme in the heme synthesis pathway. It combines glycine and succinyl-coenzyme A to produce the amino acid d-aminolevulinic acid (ALA), which is a precursor in the synthesis of heme.
4
Q
How does the synthesis of heme occur in the body, and where does the majority take place?
A
Heme synthesis occurs in 8 steps, each catalyzed by a different enzyme. The majority (85%) of heme synthesis occurs in the bone marrow to support hemoglobin formation, with the remainder primarily in the liver for cytochrome P450 enzymes.
5
Q
What is the significance of the enzyme ferrochelatase (FECH) in heme synthesis?
A
Ferrochelatase (FECH) is the final enzyme in the heme synthesis pathway. It is responsible for inserting iron into protoporphyrin IX to form heme, which is essential for the function of many hemoproteins, including hemoglobin.
6
Q
What are porphyrias caused by?
A
Abnormalities of the 8 enzymes in the heme biosynthetic pathway.
7
Q
How are porphyrias classified?
A
As hepatic or erythropoietic based on whether heme precursors accumulate in the liver or bone marrow.
8
Q
What characterizes cutaneous porphyrias?
A
Overproduction and accumulation of photosensitizing porphyrins, causing chronic blistering and scarring on sun-exposed areas of skin.
9
Q
What are acute porphyrias characterized by?
A
Neurologic symptoms and elevated levels of porphyrin precursors, d-aminolevulinic acid (ALA) and porphobilinogen (PBG).
10
Q
What is the first enzyme in the heme synthesis pathway?
A
ALAS, which combines glycine and succinyl-coenzyme A to produce d-aminolevulinic acid (ALA).
11
Q
What is the role of heme in the body?
A
Heme is the prosthetic group for many essential hemoproteins, including hemoglobin.
12
Q
What is the final enzyme in heme synthesis?
A
Ferrochelatase (FECH).
13
Q
What percentage of heme synthesis occurs in the bone marrow?
A
85%.
14
Q
What regulates heme synthesis in the liver?
A
Primarily by the activity of d-aminolevulinic acid synthase 1 (ALAS1).
15
Q
What is the most common type of porphyria and what are its key characteristics?
A
Porphyria cutanea tarda (PCT) is the most common porphyria, characterized by skin friability and chronic blistering lesions on sun-exposed areas, particularly the hands. It typically develops in mid- to late life and is associated with deficient uroporphyrinogen deaminase (UROD) activity in hepatocytes, leading to the accumulation of porphyrins. In active cases, hepatic UROD activity is reduced to less than 20% of normal.
16
Q
What are the clinical features associated with porphyria cutanea tarda (PCT)?
A
Clinical features of PCT include:
1. Development in the fourth or fifth decade of life, most commonly in males.
2. Fluid-filled blisters and bullae on sun-exposed areas, especially the dorsal hands.
3. Eroded areas prone to bacterial infection, with residual scarring and pigmentation changes.
4. Facial hypertrichosis and hyperpigmentation may occur.
5. Severe thickening of skin resembling systemic sclerosis, termed pseudoscleroderma.
6. Neurologic symptoms characteristic of acute porphyrias are absent in PCT.
17
Q
What susceptibility factors are associated with the development of porphyria cutanea tarda (PCT)?
A
Susceptibility factors for PCT include:
- Genetic factors
- Viral infections
- Chemical exposures
- Alcohol use (87% of patients)
- Smoking (81% of patients)
- Chronic hepatitis C (69% of patients)
- HFE (hematochromatosis) mutations (53% of patients)
These factors do not cause PCT by themselves but are often present in patients with the condition.
18
Q
What is the significance of UROD mutations in porphyria cutanea tarda (PCT)?
A
UROD mutations are significant in PCT as follows:
- Most PCT patients have sporadic (type 1) disease.
- Approximately 20% have a heterozygous predisposing UROD mutation, classified as familial (type 2) PCT.
- Type 2 PCT is autosomal dominant with low penetrance and requires other susceptibility factors to develop.
- HEP (homozygous form of type 2 PCT) resembles congenital erythropoietic porphyria (CEP) clinically.
19
Q
How does iron and hemochromatosis gene (HFE) mutations relate to porphyria cutanea tarda (PCT)?
A
Iron and HFE mutations relate to PCT as follows:
- Iron stores are usually normal or increased in PCT, while iron deficiency is protective.
- Iron creates an oxidative environment in hepatocytes, facilitating the generation of a UROD inhibitor.
- The C282Y mutation of the HFE gene is prevalent in PCT patients, with up to 20% being homozygotes, potentially leading to earlier onset of disease.
- HFE mutations impair sensing of serum iron, reducing hepatic hepcidin production, which affects iron absorption.
20
Q
What role does alcohol play in the onset of porphyria cutanea tarda (PCT)?
A
Alcohol and its metabolites may predispose individuals to the onset of PCT by inducing hepatic ALAS1 and cytochrome P450 enzymes (CYPs), which generate reactive oxygen species (ROS). This oxidative stress can contribute to the development of PCT in susceptible individuals.
21
Q
What is the most common type of porphyria?
A
Porphyria cutanea tarda (PCT).
22
Q
What are the characteristic skin features of PCT?
A
Development of skin friability and chronic, blistering lesions on sun-exposed areas of the skin.
23
Q
What enzyme deficiency is associated with PCT?
A
Deficient uroporphyrinogen deaminase (UROD) activity in hepatocytes.
24
Q
What is the typical age of onset for PCT?
A
In the fourth or fifth decade of life, most commonly in males.
25
What are common susceptibility factors for developing PCT?
Genetic factors, viral infections, and chemical exposures, with ethanol use being the most common.
26
What is the response of PCT to treatment?
PCT responds well to either phlebotomy or low-dose hydroxychloroquine.
27
What are the common clinical features of PCT?
Fluid-filled blisters, erosion of skin, scarring, hyperpigmentation, and facial hypertrichosis.
28
What is the relationship between iron levels and PCT?
Iron stores are always normal or increased in PCT, whereas iron deficiency is protective.
29
What is the significance of UROD mutations in PCT?
Approximately 20% of patients have a heterozygous UROD mutation, but these do not cause PCT without other susceptibility factors.
30
How does alcohol consumption relate to PCT?
Alcohol and its metabolites may predispose to the onset of PCT by inducing hepatic ALAS1 and CYPs, generating ROS.
31
A patient presents with chronic blistering lesions on sun-exposed skin. What is the most common porphyria associated with these symptoms, and what is the first-line screening test?
The most common porphyria associated with chronic blistering lesions on sun-exposed skin is Porphyria Cutanea Tarda (PCT). The first-line screening test is total plasma or urine porphyrins.
32
What role does smoking play in the development of porphyria cutanea tarda (PCT)?
Smoking is regarded as an independent risk factor for PCT. It may increase oxidative stress in hepatocytes and induces hepatic CYPs, particularly CYP1A2, which is important for the development of uroporphyria in rodent models. Hepatic CYPs are often increased in human PCT, and a more inducible CYP1A2 variant is found to be more common in PCT than in normal subjects.
33
How does estrogen influence the risk of developing porphyria cutanea tarda (PCT)?
Estrogen use is common in women with PCT, and the disease has also occurred in some men treated with estrogen for prostate cancer. Female rats or males receiving estrogens are more susceptible to chemically-induced uroporphyria than untreated males, possibly due to the generation of reactive oxygen species (ROS).
34
What is the relationship between hepatitis C and porphyria cutanea tarda (PCT)?
Hepatitis C promotes hepatocyte steatosis, iron accumulation, mitochondrial dysfunction, oxidative stress, and dysregulation of hepcidin expression. The prevalence of chronic hepatitis C in PCT ranges from 21% to 92%, exceeding the prevalence of this viral infection in the general population. However, only 0.05% of individuals with chronic hepatitis C develop PCT.
35
What are the biochemical features associated with chemical exposure and drugs in the context of porphyria cutanea tarda (PCT)?
Outbreaks of PCT have been linked to exposure to chemicals such as hexachlorobenzene and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These chemicals cause biochemical features of PCT in laboratory animals and cultured hepatocytes, indicating a significant relationship between chemical exposure and the development of PCT.
36
What is the significance of UROD activity in the pathogenesis of porphyria cutanea tarda (PCT)?
PCT develops when hepatic UROD activity is reduced to approximately 20% of normal. With enzyme inhibition, the amount of UROD protein remains at its genetically determined level in the liver. About 20% of patients are heterozygous for UROD mutations, making them more susceptible to developing PCT due to reduced UROD activity in the liver.
37
What are the first-line tests for diagnosing porphyria cutanea tarda (PCT)?
The first-line testing for diagnosing PCT involves measuring total plasma or urine porphyrins. It is essential to establish a laboratory diagnosis of PCT before initiating treatment, especially since PCT can present with similar skin lesions as other types of porphyrias.
38
What is the role of total erythrocyte porphyrins in the diagnosis of PCT?
Total erythrocyte porphyrins are usually normal or modestly elevated in PCT. Markedly elevated levels may indicate rare cases of CEP, HEP, or homozygous HCP or VP, which typically present in infancy but can manifest in adults.
39
What factors should be assessed in patients with PCT regarding susceptibility?
Patients with PCT should be assessed for susceptibility factors such as:
- Alcohol and estrogen use
- Smoking
- Hepatitis C and HIV infection
- HFE and UROD mutations
These factors can influence the disease and its management.
40
What is the preferred treatment for PCT and how is it monitored?
The preferred treatment for PCT is phlebotomy to reduce hepatic iron. It is monitored by measuring serum ferritin levels, aiming for a target of 15 to 20 ng/mL. Phlebotomies are typically performed every two weeks, and the number of sessions required for remission is usually between 6 to 8.
41
What are the clinical implications of using hydroxychloroquine in PCT treatment?
A low-dose regimen of hydroxychloroquine is an effective alternative to phlebotomies in treating PCT. It mobilizes porphyrins accumulated in lysosomes and other intracellular organelles in hepatocytes without depleting hepatic iron, but full therapeutic doses can rapidly mobilize porphyrins and induce acute hepatitis.
42
How often are phlebotomies performed for PCT?
Phlebotomies are typically performed every two weeks.
43
How many phlebotomy sessions are usually required for remission in PCT?
The number of sessions required for remission is usually between 6 to 8.
44
What is the clinical implication of using hydroxychloroquine in PCT treatment?
A low-dose regimen of hydroxychloroquine is an effective alternative to phlebotomies in treating PCT.
45
What does hydroxychloroquine do in PCT treatment?
It mobilizes porphyrins accumulated in lysosomes and other intracellular organelles in hepatocytes without depleting hepatic iron.
46
What can full therapeutic doses of hydroxychloroquine induce?
Full therapeutic doses can rapidly mobilize porphyrins and induce acute hepatitis.
47
What is the significance of fluorescence scanning of diluted plasma in diagnosing porphyrias?
It helps to identify the porphyria most commonly misdiagnosed as PCT, which is VP, by detecting an emission peak at approximately 626 nm.
48
What urine test results are indicative of PCT?
A predominance of uroporphyrin, hepta-, hexa-, and pentacarboxyl porphyrins in urine.
49
What is the role of total erythrocyte porphyrins in diagnosing PCT?
They are normally or modestly elevated in PCT, but markedly elevated in rare cases of CEP, HEP, or homozygous HCP or VP.
50
Why is measuring serum ferritin important in PCT patients?
Serum ferritin should be measured as it may influence the choice of treatment and helps in monitoring the condition.
51
What treatment options are effective for PCT?
Phlebotomy or low-dose hydroxychloroquine is highly effective in both sporadic and familial forms of PCT.
52
What factors should be identified in PCT patients?
Patients should be questioned or examined for susceptibility factors such as alcohol and estrogen use, smoking, hepatitis C, HIV infection, and HFE and UROD mutations.
53
What is the recommended approach for managing elevated porphyrin levels in PCT?
Repeated phlebotomy to reduce hepatic iron is the preferred treatment, guided by serum ferritin levels.
54
What is the expected outcome after phlebotomy treatment in PCT patients?
Most patients require 6 to 8 phlebotomies for biochemical and clinical remission.
55
What should be monitored during phlebotomy sessions for PCT?
Measurement of hematocrit and ferritin at each session allows monitoring to prevent symptomatic anemia and assess progress toward the target ferritin level.
56
What is the potential consequence of resuming alcohol use in PCT patients?
Relapse of PCT may occur, often related to resumption of alcohol use, but usually responds to retreatment.
57
What is the recommended low-dose regimen for treating PCT?
A low-dose regimen of hydroxychloroquine 100 mg or chloroquine 125 mg (one half of a standard tablet) twice weekly is recommended.
58
What are the clinical features associated with hepatocutaneous porphyria (HEP)?
The clinical features of HEP include blistering skin lesions, hypertrichosis, scarring, hemolytic anemia, red urine, and sclerodermoid skin changes.
59
What is the significance of erythrocyte UROD activity in hepatocutaneous porphyria (HEP)?
In HEP, erythrocyte UROD activity is markedly diminished, typically ranging from 5% to 30% of normal.
60
What are the recommended therapies for patients with hepatocutaneous porphyria (HEP)?
Recommended therapies include avoiding sunlight, phlebotomy, hydroxychloroquine, oral charcoal in severe cases, and potential gene replacement therapy.
61
What are the clinical features of Hepatoerythropoietic Porphyria (HEP)?
Onset of blistering skin lesions, hypertrichosis, scarring, hemolytic anemia, and red urine typically in early childhood.
62
What is the relationship between PCT and hepatitis C treatment?
PCT should be treated first, which is usually more symptomatic, before treating coexisting hepatitis C.
63
What is the significance of UROD mutations in Hepatoerythropoietic Porphyria?
Inherited UROD mutations from each parent lead to decreased UROD activity, which is 5% to 30% of normal in HEP.
64
What are the biochemical findings in HEP?
Predominant accumulation and excretion of uroporphyrin, heptacarboxyl porphyrin, and isocoproporphyrins, with increased erythrocyte zinc protoporphyrin.
65
What therapy is suggested for patients with Hepatoerythropoietic Porphyria?
Patients should avoid sunlight, and phlebotomy and hydroxychloroquine have shown little or no benefit.
66
What is the role of oral charcoal in treating HEP?
Oral charcoal was helpful in a severe case associated with dyserythropoiesis.
67
What screening should be included for patients with PCT associated with end-stage renal disease?
Periodic screening for hepatocellular carcinoma should include liver imaging by abdominal ultrasound or CT.
68
What is the underlying cause of Günther disease (CEP)?
Günther disease is caused by a substantial deficiency of the enzyme UROS.
69
What are the clinical features of Congenital Erythropoietic Porphyria (CEP)?
Clinical features include subepidermal bullous lesions, scarring, hyper- and hypopigmentation, and erythrodontia.
70
How is Congenital Erythropoietic Porphyria (CEP) diagnosed?
Diagnosis can be made through detection of large amounts of porphyrins in amniotic fluid or fetal blood.
71
What are the treatment options for Congenital Erythropoietic Porphyria (CEP)?
Treatment options include avoidance of sunlight, erythrocyte transfusions, hydroxyurea, splenectomy, and hematopoietic stem cell transplantation.
72
What is Gunther disease also known as?
Gunther disease is also known as CEP (Congenital Erythropoietic Porphyria).
73
What causes the symptoms of Gunther disease?
A substantial deficiency of the enzyme UROS leads to the accumulation of porphyrins.
74
What are the clinical features of Gunther disease?
Subepidermal bullous lesions affecting light-exposed areas, often leading to scarring.
75
How can Gunther disease be diagnosed?
It can be recognized in utero by large amounts of porphyrins measured in amniotic fluid.
76
What is a common treatment option for severe cases of Gunther disease?
Hematopoietic stem cell transplantation is curative for young patients with severe disease.
77
What role does sunlight play in Gunther disease?
Patients are advised to avoid sunlight to prevent severe scarring and loss of facial features.
78
What are some laboratory findings in patients with Gunther disease?
Increased urinary, erythrocyte, and plasma porphyrins, with a predominance of uroporphyrin I and coproporphyrin I.
79
What complications can arise from untreated anemia in Gunther disease?
Uncorrected anemia can stimulate erythropoiesis and contribute to increased porphyrin production.
80
What is the significance of porphyrin accumulation in Gunther disease?
Porphyrin accumulation leads to cell damage due to exposure to light.
81
What is erythropoietic protoporphyria (EPP) and what causes it?
EPP is the most common type of porphyria in children, resulting from a loss-of-function mutation of FECH.
82
What are the clinical features of acute cutaneous photosensitivity in EPP?
Acute cutaneous photosensitivity is characterized by stinging pain, erythema, and edema.
83
What is the significance of FECH mutations in the pathogenesis of EPP?
FECH mutations lead to the accumulation of protoporphyrin in marrow reticulocytes.
84
What complications can arise from protoporphyric hepatopathy in EPP patients?
Protoporphyric hepatopathy can lead to chronic liver function abnormalities and may require urgent liver transplantation.
85
How does the inheritance pattern of X-linked protoporphyria (XLP) differ from EPP?
XLP results from a gain-of-function mutation of ALAS2, while EPP is primarily caused by loss-of-function mutations in FECH.
86
What is the inheritance pattern of EPP?
EPP is primarily autosomal recessive, requiring mutations in both FECH alleles.
87
What is the role of FECH in the heme biosynthetic pathway?
FECH is the last enzyme in the heme biosynthetic pathway, and its deficiency leads to protoporphyrin accumulation.
88
What are the effects of sunlight exposure on patients with EPP?
Patients experience acute cutaneous photosensitivity, with symptoms worsening during spring and summer.
89
What is the significance of the ALAS2 mutation in protoporphyria?
Mutations in ALAS2 lead to increased enzymatic activity and accumulation of protoporphyrin IX.
90
What are the histopathological findings in skin affected by EPP?
Thickened capillary walls in the papillary dermis with deposition of amorphous hyaline-like and PAS-positive mucopolysaccharides.
91
What are the common skin changes associated with erythropoietic protoporphyria (EPP)?
Common skin changes may include leathery hyperkeratotic skin, mild scarring, and separation of the nail plate.
92
How does pregnancy affect erythrocyte protoporphyrin levels in patients with EPP?
Pregnancy is reported to lower erythrocyte protoporphyrin levels somewhat and increase tolerance to sunlight.
93
What is the primary therapeutic intervention for erythropoietic protoporphyria (EPP)?
The primary therapeutic intervention for EPP is photoprotection.
94
What laboratory measurements are important for diagnosing erythropoietic protoporphyria (EPP)?
Key laboratory measurements include total erythrocyte protoporphyrin levels and proportions of metal-free and zinc protoporphyrin.
95
What are key laboratory measurements for diagnosing erythropoietic protoporphyria (EPP)?
Key laboratory measurements for diagnosing EPP include total erythrocyte protoporphyrin levels, proportions of metal-free and zinc protoporphyrin, and a plasma fluorescence peak of diluted plasma at neutral pH near 634 nm.
96
What dietary recommendations are suggested for patients with erythropoietic protoporphyria (EPP)?
Daily intake of 800 IU of vitamin D and 1000 mg of calcium is recommended because EPP patients must avoid sunlight exposure.
97
What is the average erythrocyte protoporphyrin level in male patients with XLP compared to those with EPP?
Male patients with XLP have higher erythrocyte protoporphyrin levels (3574 μg/dL) than patients with EPP (1669 μg/dL).
98
What skin changes are commonly seen in patients with protoporphyria due to sunlight exposure?
Chronic skin changes are uncommon but may include leathery hyperkeratotic skin, mild scarring, labial grooving, and separation of the nail plate.
99
How does pregnancy affect erythrocyte protoporphyrin levels in patients?
Pregnancy is reported to lower erythrocyte protoporphyrin levels somewhat and increase tolerance to sunlight.
100
What is the primary therapeutic intervention for EPP?
Photoprotection, especially avoidance of sunlight exposure, is the primary therapeutic intervention in EPP.
101
What is the role of beta-carotene in the treatment of EPP?
Orally administered beta-carotene is thought to quench activated oxygen radicals and can increase sunlight tolerance.
102
What should be monitored yearly in patients with EPP?
Erythrocyte and plasma porphyrin levels, liver function tests, serum ferritin, and serum vitamin D levels should be monitored yearly.
103
What is a unique finding in erythrocyte protoporphyrin levels in protoporphyrias?
An increase in erythrocyte protoporphyrin comprised predominantly of metal-free protoporphyrin is a finding unique to protoporphyrias.
104
What is the effect of prolonged surgery on patients with hepatopathy?
Operating room lights during prolonged surgery can cause marked photosensitivity with extensive burns of the skin and peritoneum.
105
What is the significance of measuring total erythrocyte protoporphyrin?
Measurement of total erythrocyte protoporphyrin helps establish or exclude the diagnosis of protoporphyria.
106
What are the four acute porphyrias and their associated enzyme deficiencies?
The four acute porphyrias are: 1. D-aminolevulinate dehydratase deficiency porphyria (ADP) - deficiency in the second enzyme. 2. Acute intermittent porphyria (AIP) - deficiency in the third enzyme. 3. Hereditary coproporphyria (HCP) - deficiency in the sixth enzyme. 4. Variegate porphyria (VP) - deficiency in the seventh enzyme.
107
What are the clinical features associated with acute hepatic porphyrias?
Typical neurovisceral manifestations of acute hepatic porphyrias include abdominal pain, vomiting, extremity pain, seizures, and muscle weakness due to motor neuropathy.
108
What factors can precipitate acute attacks in acute hepatic porphyrias?
Known endogenous and exogenous factors that can precipitate acute attacks include induction of hepatic ALAS1, drugs that induce hepatic CYPs and ALAS1, smoking, and ethanol.
109
What is the inheritance pattern of acute porphyrias and their prevalence?
ADP: Autosomal recessive, extremely rare. AIP: Autosomal dominant with low penetrance, prevalence of 1 to 2 per 100,000 in Europe. HCP: Autosomal dominant, prevalence of 0.2 per 100,000 in Denmark. VP: Autosomal dominant, prevalence of 1.3 per 100,000 in Finland.
110
What is the role of PBGD and other enzymes in the heme biosynthetic pathway?
PBGD catalyzes the assembly of HMBS from 4 molecules of PBG. CPOX catalyzes the oxidative decarboxylation of coproporphyrinogen III. PPOX catalyzes the dehydrogenation of protoporphyrinogen IX.
111
What is the most common acute hepatic porphyria worldwide?
Acute intermittent porphyria (AIP).
112
What is the most effective treatment for acute attacks in acute hepatic porphyrias?
Hemin is the most effective treatment for acute attacks in acute hepatic porphyrias.
113
What is the target serum ferritin level for patients on repeated phlebotomy?
The target serum ferritin level for patients on repeated phlebotomy is typically around 50-100 ng/mL.
114
What is the first line screening test for PCT?
The first line screening test for PCT is urinary porphyrins or plasma porphyrins.
115
What susceptibility factor is common in female patients with PCT?
The common susceptibility factor in female patients with PCT is estrogen exposure.
116
What is the homozygous form of Type 2 familial PCT?
The homozygous form of Type 2 familial PCT is X-linked porphyria (XLP).
117
What is the recommended daily intake of vitamin D and calcium for EPP patients?
Daily intake of 800 IU of vitamin D and 1000 mg of calcium is recommended for EPP patients to avoid sunlight exposure.
118
What is the treatment of choice for young patients with severe disease in porphyria?
Hemin therapy is curative and is the treatment of choice for young patients with severe disease.
119
Which type of porphyria is characterized by skin friability and chronic, blistering lesions on sun-exposed skin?
The most common porphyria characterized by skin friability and chronic, blistering lesions on sun-exposed skin is porphyria cutanea tarda (PCT).
120
What is the most common porphyria characterized by skin friability and blistering lesions on sun-exposed skin?
Porphyria cutanea tarda (PCT).
121
What treatments are highly effective in both sporadic and familial forms of PCT?
Phlebotomy or hydroxychloroquine.
122
What is the significance of the fecal coproporphyrin III/I ratio in diagnosing HCP?
The fecal coproporphyrin III/I ratio is sensitive for the diagnosis of HCP, even in asymptomatic stages of the disease.
123
What are the common symptoms managed in outpatient settings for milder recurring attacks of porphyria?
Milder recurring attacks that respond rapidly to treatment are sometimes managed as outpatients, often involving the removal of precipitating factors and symptomatic treatment.
124
What is the relationship between estrogen and porphyria susceptibility?
Estrogen use is a common susceptibility factor in women with porphyria cutanea tarda (PCT).
125
How can starvation affect porphyria?
Starvation may induce hepatic heme oxygenase, which may deplete hepatic heme and contribute to ALAS1 induction.
126
What is the significance of urinary PBG levels during acute attacks of AIP, HCP, and VP?
Urinary PBG is elevated during acute attacks of AIP, HCP, and VP, but often less so and more transiently in HCP and VP than in AIP.
127
What is a common treatment for acute attacks of porphyria?
Hospitalization is usually advisable for treatment of severe symptoms during acute attacks of porphyria.
128
What is the role of sunlight avoidance in the management of porphyria?
Avoidance of sunlight and use of protective clothing is most important in managing cutaneous manifestations of porphyria.
129
What potentially fatal complication occurs in less than 5% of patients with EPP?
Severe liver disease.
130
True or false: Treatment of this type of porphyria includes phlebotomy or low dose hydroxychloroquine.
True.
131
What is the most common type of porphyria in children?
Erythropoietic protoporphyria (EPP).
132
True or false: In EPP, bullae and skin fragility are rare.
True.
133
What is the recommended daily intake of vitamin D and calcium for EPP patients?
1000 IU of vitamin D and 1000 mg of calcium.
134
Among the acute hepatic porphyrias, which commonly present with chronic blistering skin lesions?
Porphyria cutanea tarda (PCT).
135
What method distinguishes a specific feature of VP and differentiates it from PCT?
Urinary porphyrin profiling.
136
What is the daily intake of vitamin D and calcium for EPP patients?
1000 IU of vitamin D and 1000 mg of calcium
137
Among the acute hepatic porphyrias, which commonly present with chronic blistering skin lesions?
Porphyria cutanea tarda (PCT)
138
What method distinguishes a specific feature of VP and differentiates it from PCT?
Urinary porphyrin profiling
139
What is the most common acute hepatic porphyria worldwide?
Acute intermittent porphyria (AIP)
140
What is the most effective treatment for acute attacks in acute hepatic porphyrias?
Hemin
141
What is another treatment option for acute hepatic porphyrias given for mild attacks, but is less effective than hemin?
Carbohydrate loading
142
What are the principal clinical features of X-linked protoporphyria (XLP)?
**Nonblistering photosensitivity** is the principal clinical feature of X-linked protoporphyria (XLP).
143
What is the inheritance pattern of Acute Intermittent Porphyria (AIP)?
Acute Intermittent Porphyria (AIP) follows an **autosomal dominant** inheritance pattern.
144
What differentiates the clinical features of Porphyria Cutanea Tarda (PCT) from other porphyrias?
Porphyria Cutanea Tarda (PCT) is characterized by **blistering photosensitivity** and is associated with **121 known mutations** including those related to Hepatoerythropoietic Porphyria (HEP).
145
What is the urine test result for patients with Hereditary Coproporphyria (HCP)?
In patients with Hereditary Coproporphyria (HCP), the urine test typically shows **coproporphyrin** levels that are **increased** or **slightly increased**.
146
What is the classification of Erythropoietic Protoporphyria (EPP)?
Erythropoietic Protoporphyria (EPP) is classified as **autosomal recessive** and is characterized by **nonblistering photosensitivity**.
147
What type of inheritance is associated with Acute intermittent porphyria (AIP)?
Autosomal dominant.
148
Which porphyria is classified as autosomal recessive and involves Uroporphyrinogen III synthase (UROS)?
Congenital erythropoietic porphyria (CEP).
149
What is the classification of Porphyria cutanea tarda (PCT)?
Autosomal dominant.
150
What is the known mutation associated with Hereditary coproporphyria (HCP)?
Coproporphyrinogen oxidase (CPOX).
151
What is the inheritance pattern of Erythropoietic protoporphyria (EPP)?
Autosomal recessive.
152
What is the principal clinical feature of Hereditary erythropoietic porphyria (HEP)?
Blistering photosensitivity.
153
What is the known mutation for 5-Aminolevulinic acid dehydratase porphyria (ALAD)?
ALAD enzyme deficiency.
154
What is the urine finding for patients with Variegate porphyria (VP)?
Uroporphyrin, coproporphyrin I.
