Porphyria by Dr. Basil Tumaini

Acute Intermittent Porphyria,
and Cutaneous, Hepatic and
Erythropoietic Porphyrias
Dr. Tumaini, Basil B
MD, MMED Resident
Muhimbili University of Health and Allied Sciences
10 August 2017 Porphyrias 1

Presentation outline
• Porphyrias Overview
– Definition
– Heme biosynthesis pathway
– Classification
– Etiology
– Pathophysiology
– Clinical features
• Acute intermittent porphyria
• Porphyria Cutanea Tarda
• Hepatoerythropoietic porphyria

Background
• Chemistry of porphyrins
• Photochemistry of porphyrins
• Phototoxicity of porphyrins

The heme
molecule

• Around 80% of heme is synthesized in
erythroid cell precursors in the bone marrow
(for Hg production).
• Decarboxylation of uroporphyrinogen to
coproporphyrinogen and thence to
protoporphyrinogen decreases water
solubility
– uroporphyrinogen is only excreted via the kidneys
– hydrophobic protoporphyrinogen and
protoporphyrin are exclusively excreted into the
bile
– Coproporphyrinogen is excreted by both routes

• Physiological concentrations of porphyrins
stay low because of the high efficiency of
haem synthesis.

The classification of the porphyrias
1. Cutaneous disease only:
 Porphyria cutanea tarda (PCT)
 Congenital erythropoietic porphyria (CEP)
 Erythropoietic protoporphyria (EPP)
2. Cutaneous disease and acute attacks:
 Hereditary coproporphyria (HC)
 Variegate porphyria (VP)
3 Acute attacks only:
 Acute intermittent porphyria (AIP)

Porphyrias
• Porphyria is named from the ancient Greek word
porphura, meaning purple
• Porphyrias are metabolic disorders resulting from
genetic or acquired deficiencies of enzymes of the
heme biosynthetic pathway
• Porphyrias are defined by the specific enzyme
deficiency
• Two major clinical manifestations occur:
– Neurovisceral abnormalities (the acute porphyrias) and
– Cutaneous photosensitivity (the cutaneous porphyrias)

Heme biosynthesis
• Heme is an essential cofactor of numerous
hemoproteins.
• Virtually all cells of the human body require and
synthesize heme.
– Mostly in the bone marrow (by erythroblasts and
reticulocytes) and is incorporated into Hb (85 – 90%).
– And in the liver in which it is incorporated into
cytochrome P-450 enzymes (10 – 15%).
• Heme synthesis requires 8 enzymes

PORPHYRIAS
GLYCINE + SuccinylCoA
d-aminolevulinic acid(ALA)
Porphobilinogen(PBG)
hydroxymethylbilane
uroporphyrinogen III
coprophyrinogene III
Protoporphyrinogene IX
protoporphyrin IX
Heme
ALA synthase
ALA dehydratase
PBG deaminase
Uroporphyrinogen III
cosynthase
Uroporphyrinogen
decarboxylase
Coproporphyrinogen
oxidase
Protoporphyrinogen
oxidase
Ferrochelatase
ALA-dehydratase
Deficiency porphyria
Acute intermittent
porphyria
Congenital erythropoietic
porphyria
Prophyria
cutanea tarda
Herediatary
coproporphyria
Variegate
porphyria
Erythropoietic
protoporphyria
Mitochondria

Etiology
• The porphyrias are inherited diseases
– Exception: the sporadic type of porphyria cutanea tarda (PCT)
– Pattern of inheritance: Autosomal dominant is the most common
• The 2 most common porphyrias:
– PCT (20% of PCT is autosomal dominant)
– Acute intermittent porphyria (AIP)
• The prevalence
– PCT 1/10,000
– AIP 1/10,000
– AIP genetic mutation 1/1500
• The 3rd most common porphyria – erythropoietic
protoporphyria
– Autosomal recessive

Pathophysiology
• Porphyrias result from a deficiency of any of the last 7
enzymes of the heme biosynthetic pathway or from
increased activity of the first enzyme in the pathway, ALA
synthase-2 (ALAS 2).
– Deficiency of ALAS 2 causes sideroblastic anemia rather than
porphyria.
• Single genes encode each enzyme
• When an enzyme of heme synthesis is deficient or defective,
heme precursors may accumulate in bone marrow, liver,
skin, or other tissues and have toxic effects.
• These precursors may appear in excess in the blood and be
excreted in urine, bile, or stool.

PORPHYRIAS
hydroxymethylbilane
protoporphyrin IX
Heme
ALA synthase
ALA dehydratase
PBG deaminase
cosynthase
Uroporphyrinogen
decarboxylase
Coproporphyrinogen
oxidase
Protoporphyrinogen
oxidase
Ferrochelatase
ALA-dehydratase
Acute intermittent
porphyria
porphyria
Prophyria
cutanea tarda
Herediatary
coproporphyria
Variegate
porphyria
Erythropoietic
protoporphyria
Mitochondria

Clinical features
• Porphyrias are classified by major clinical features
(phenotype) into 2 classes:
– Acute
– Cutaneous
• Acute porphyrias
– Manifest as intermittent attacks of abdominal, mental, and
neurologic symptoms
– Triggered by drugs, cyclic hormonal activity in young women,
and other exogenous factors
• Cutaneous porphyrias
– Cause continuous or intermittent symptoms involving cutaneous
photosensitivity
– Some acute porphyrias (hereditary coproporphyria, variegate
porphyria) may also have cutaneous manifestations

• Urine discoloration (red or reddish brown) may
occur in the symptomatic phase of all porphyrias
except erythropoietic protoporphyria (EPP) and
ALAD-deficiency porphyria.
– Discoloration results from oxidation of the
porphyrinogens, the porphobilinogen (PBG), or
both.
– Sometimes the color develops after the urine has stood
in light for about 30 min, allowing time for non-
enzymatic oxidation.

Acute intermittent porphyria

Acute intermittent porphyria
• An autosomal dominant disorder resulting from a
partial deficiency of porphobilinogen
deaminase, the third enzyme in the heme
biosynthetic pathway
– For conversion of porphobilinogen to
hydroxymethylbilane.
• In AIP, there accumulation of the porphyrin
precursors:
– Porphobilinogen and amino-levulinic acid (ALA)

PORPHYRIAS
hydroxymethylbilane
protoporphyrin IX
Heme
ALA synthase
ALA dehydratase
PBG deaminase
cosynthase
Uroporphyrinogen
decarboxylase
Coproporphyrinogen
oxidase
Protoporphyrinogen
oxidase
Ferrochelatase
ALA-dehydratase
Acute intermittent
porphyria
porphyria
Prophyria
cutanea tarda
Herediatary
coproporphyria
Variegate
porphyria
Erythropoietic
protoporphyria
Mitochondria

• The predominant problem appears to be
neurologic damage that leads to peripheral
and autonomic neuropathies and psychiatric
manifestations
• How the elevations of porphobilinogen and
ALA leads to the symptomatic disease is still
unclear
– Most patients with the genetic defect have
excessive porphyrin secretion but no symptoms

Epidemiology
• Prevalence not known in our setting
– US: 1-5/ 100,000
– Northern Sweden: 60-100/ 100,000
• Most patients become symptomatic at age 18-
40 years.
– Attacks occurring before puberty or after age 40
years are unusual
• Women to men ratio 1.5–2: 1

Genetics
• Autosomal dominant
• Variable penetrance
– The genetic defect is more common than symptomatic
AIP
– Out of 100 patients with the genetic defect, ≈10-20
secrete excess porphyrin precursors and only 1-2 have
symptoms
• In patients with AIP, the function of
porphobilinogen-deaminase is only 40-60% of
normal

Clinical features
• The sequence of events in attacks of AIP usually is as
follows:
– Abdominal pain
– Psychiatric symptoms (e.g., hysteria)
– Peripheral neuropathies, mainly motor neuropathies
• Most patients are completely free of symptoms
between attacks.
• Attacks in AIP develop over hours or days and persist
for days or weeks, depending upon precipitating
factors and treatment
• There are no cutaneous manifestations

• Neurovisceral signs and symptoms: autonomic
neuropathies
– Constipation, abdominal pain, vomiting, or hypertension
and tachycardia
• The abdominal pain often is epigastric and colicky
in nature
• Central nervous system signs may include the
following:
– Seizures, delirium, cortical blindness, coma
• Peripheral neuropathies that are predominantly
motor mimicking Guillain-Barré syndrome
– The weakness usually ascending starting in the lower
limbs

• Electrolyte and metabolic abnormalities
– Hyponatremia due to
• Hypothalamic involvement
• SIADH
• Gastrointestinal or renal sodium loss
– Hypomagnesemia
– Hypercalcemia

Precipitating factors
• Chemicals or situations that boost heme synthesis.
• Drugs that lead to increased activity of the hepatic
P450 system are a/w porphyria:
– Phenobarbital, sulfonamides, estrogens, and alcohol
• Fasting
• Infections
• Organic solvents
• Stress

Diagnosis
• Because the presenting symptoms and signs are
nonspecific, a high index of suspicion is required
for the initial diagnosis of acute porphyria
• 1st line screening test, urinary porphobilinogen
(PBG) is cost effective

Urinary porphobilinogen (PBG)
• The diagnosis of AIP, hereditary coproporphyria
(HCP), or variegate porphyria (VP) can be ruled
in or out by assessing urinary PBG
• Low levels (0 to 4 mg/L) during acute symptoms
exclude porphyria
• During an acute attack of AIP, urinary PBG
excretion is generally 20 to 200 mg/day
– Normal 0 to 4 mg/day or per gram of creatinine
• PBG may not be elevated when the patient with
AIP is asymptomatic

Other tests
• If a screening test for increased urinary PBG is
negative on a spot urine specimen but the
index of suspicion is high for an acute
porphyria,
– 24-hour urine collection for quantitative
assessment of delta-aminolevulinic acid (ALA),
PBG, and total porphyrins.
• DNA testing

Management
Management includes
• Treatment of acute attacks
• Prevention of acute attacks
• Long-term monitoring
• Genetic counseling

Treatment of Acute Attack
• Treatment of symptoms
• Carbohydrate loading
• IV hemin
• Liver transplantation
• Other therapies

Treatment of symptoms
• Drugs known to be harmful in patients with AIP
should be avoided whenever possible
• Narcotic analgesics, chlorpromazine, or another
phenothiazine or ondansetron
– For severe pain, nausea, and vomiting
• Short-acting benzodiazepines in low doses
– For anxiety and insomnia
• Beta-adrenergic blocking agents
– To control tachycardia and hypertension
– But avoid in hypovolemia or incipient cardiac failure

• Anticonvulsant drugs and correcting
hyponatremia
– For seizure control
– Almost all anticonvulsants have at least some
potential for exacerbating acute porphyrias
– Clonazepam may be less harmful than phenytoin,
barbiturates or valproic acid
– Bromides, gabapentin, and vigabatrin are safe

Carbohydrate loading
• Glucose and other carbohydrates reduce
porphyrin precursor excretion
– IV glucose 300 to 500 grams administered as a 10%
solution
• Indicated for only attacks with mild pain and
without severe manifestations (eg, no paresis or
hyponatremia present)

IV hemin
• Hemin is also a generic term for heme preparations
used as IV therapies for acute porphyrias
– Heme (ferrous protoporphyrin IX) is readily oxidized in
vitro to hemin
• When infused hemin becomes bound to albumin as
heme albumin, and some is bound to hemopexin.
• These are taken up primarily by hepatocytes, where
the heme component reconstitutes the regulatory heme
pool.
• This leads to repression of the synthesis of hepatic
ALAS, followed by dramatic reductions in ALA and
PBG in plasma and urine

• The standard regimen for the acute attack is 3
to 4 mg/kg of hemin daily for four days.
• Adverse effects:
– Infusion-site phlebitis
– Coagulopathy
– Other SEs: fever, aching, malaise, hemolysis,
anaphylaxis, and circulatory collapse
– Rare SEs: reversible acute renal tubular damage,
iron overload
Stabilization with 25% human albumin can prevent
these adverse effects

Liver transplantation
• This may be an option for severely affected
patients without advanced motor weakness.

Other therapies
• Cimetidine is a cost-effective alternative to hemin
for treating acute attacks
– Cimetidine inhibits hepatic CYPs, and can prevent
experimental forms of porphyria induced by
chemicals that are activated by CYPs
• However, it cannot be recommended as an
alternative to hemin
– Since human porphyrias are not chemically induced

Prevention of acute attacks
• Avoid exposure to harmful drugs in treating intercurrent
illnesses or symptoms
• Prompt treatment of intercurrent diseases or infections
• Smoking cessation should be recommended
• A well-balanced diet somewhat high in carbohydrate (60 to
70% of total calories)
– Additional dietary carbohydrate unlikely to be helpful
• Correct iron deficiency
– It might further impair heme synthesis
• Hemin prophylaxis once or twice weekly
– Prevent frequent, non-cyclic attacks of porphyria in some
patients

Long-term monitoring
• Patients with AIP are at risk for developing CKD
and hepatocellular carcinoma
• Current recommendations are that patients > 50
years of age with acute porphyrias should be
screened by hepatic imaging at least annually for
early detection of hepatocellular carcinoma

Porphyria cutanea tarda and
hepatoerythropoietic porphyria

Introduction
• Porphyria cutanea tarda (PCT) and hepatoerythropoietic
porphyria (HEP) are porphyric conditions due to deficient
activity of uroporphyrinogen decarboxylase (UROD), the
fifth enzyme in the heme biosynthetic pathway
• Both are a/w chronic blistering photosensitivity, but are
otherwise different clinically
– PCT is sporadic, relatively more common and has adult onset
– HEP is a rare autosomal recessive form of familial PCT, presents
in childhood, and is a/w more severe UROD deficiency

PORPHYRIAS
hydroxymethylbilane
protoporphyrin IX
Heme
ALA synthase
ALA dehydratase
PBG deaminase
cosynthase
Uroporphyrinogen
decarboxylase
Coproporphyrinogen
oxidase
Protoporphyrinogen
oxidase
Ferrochelatase
ALA-dehydratase
Acute intermittent
porphyria
porphyria
Prophyria
cutanea tarda
Herediatary
coproporphyria
Variegate
porphyria
Erythropoietic
protoporphyria
Mitochondria

Porphyria cutanea tarda

Definition
• Acquired deficiency of hepatic uroporphyrinogen
decarboxylase (UROD)
– An inherited deficiency of UROD contributes in some
cases
• Defined both by clinical features and biochemical
findings
– The chronic blistering skin manifestations are
characteristic, but not specific.
– Highly carboxylated porphyrins (mostly uroporphyrin and
heptacarboxyl porphyrins) accumulate in large amounts in
the liver and then appear in plasma and urine

PORPHYRIAS
hydroxymethylbilane
protoporphyrin IX
Heme
ALA synthase
ALA dehydratase
PBG deaminase
cosynthase
Uroporphyrinogen
decarboxylase
Coproporphyrinogen
oxidase
Protoporphyrinogen
oxidase
Ferrochelatase
ALA-dehydratase
Acute intermittent
porphyria
porphyria
Prophyria
cutanea tarda
Herediatary
coproporphyria
Variegate
porphyria
Erythropoietic
protoporphyria
Mitochondria

History
• In 1911, Gunther classified adults with painful skin
lesions on sun-exposed areas of skin and increased
porphyrin levels as chronic hematoporphyria
• In 1937, Waldenstrom renamed the condition
“porphyria cutanea tarda”
• In the 1950s, exposure to hexachlorobenzene, a
fungicide, caused an outbreak of PCT in thousands of
adults and children in eastern Turkey.
– Hexachlorobenzene and other chlorinated polyaromatic
hydrocarbons can cause a deficiency of hepatic UROD
activity

Epidemiology
• PCT is reported worldwide
• Is the most common human porphyria
• Presents in mid or late life
– Onset is usually after age of 30, and is rare in children
– Earlier onset is noted in some patients with UROD
mutations or HFE mutations
• The human disease has been a/w
– Excess alcohol consumption, estrogen use, hepatic
siderosis, hepatitis C, HIV, and smoking

Pathogenesis I
2 types exist
• Type 1 (sporadic) PCT
– No UROD mutations
• Type 2 (familial) PCT
– Account for ≈ 20% of PCT cases
– Heterozygous for inherited UROD mutations
– Autosomal dominant condition with low
penetrance

Pathogenesis II
• Decreased hepatic UROD activity
– In both type 1 and 2 PCT, the disease becomes
manifest when hepatic UROD is inhibited (with its
activity < 20% of normal), likely due to the presence of
a uroporphomethene
– Generation of this inhibitor requires a normal or
increased amount of iron in the liver
oIt is not understood how iron contributes to generation of the
uroporphomethene

Pathogenesis III
• Porphyrin accumulation
– Markedly decreased activity of hepatic UROD
leads to accumulation of large amounts of
uroporphyrinogen and hepta-, hexa-, and penta-
carboxyl porphyrinogen in the liver
oAppear in plasma and urine

Clinical features
• PCT is primarily characterized by manifestations
due to skin and liver involvement.

Skin findings
• Cutaneous manifestations of PCT include vesicles,
bullae, increased fragility, scarring and hyper- and
hypopigmentation affecting sun-exposed areas of the
body, such as the backs of the hands, forearms, face,
ears, neck, and feet
– Bullae contain porphyrin-rich serous or serosanguinous
fluid, and may be painful and become infected
• Hirsutism is also common, especially on the cheeks
and forearms
• Scarring may progress to “pseudoscleroderma” and
with contraction and calcification resembling the
cutaneous findings in systemic scleroderma

“Pseudoscleroderma”
“Vempire Disease”

Photosensitivity
• Porphyrins accumulating in the skin in PCT are
photosensitizing.
• On exposure to 400 nm light
 porphyrins enter an excited state and release photons
 reactive oxygen species
 which damages proteins, lipids, and basement membranes
 complement activation, mast cell degranulation, and
release of transforming growth factor (TGF)-beta
 subepidermal blister formation and deposition of
amorphous hyaline material containing Ig around the vessel
walls

Hepatic findings
• Almost always a/w mild elevations in serum ALT and AST
• Advanced liver disease
– Uncommon at initial presentation
– May be seen in older patients with recurrent disease
• Hepatic injury in PCT can result from both
– Porphyrin accumulation (uroporphyrin and heptacarboxyl
porphyrin)
– Some of the important susceptibility factors (eg, alcohol,
hepatitis C virus)
• Histopathological findings non specific
– Siderosis, steatosis, portal triaditis, focal lobular necrosis, and
periportal fibrosis
• PCT patients have an  long-term risk for cirrhosis and
HCC

Susceptibility factors
• Genetic susceptibility
– 20% of PCT cases have inherited a mutation in the UROD
enzyme
– Mutations in the HFE gene and CYP1A2 variants
• Iron
– Enhences the generation of UROD inhibitor
• Alcohol
– Down-regulation of hepcidin increasing oxidative stress
– Induction of cytochrome P450 enzymes (CYPs)

• Smoking and cytochrome P450 enzymes
– Exposure to polycyclic aromatic hydrocarbons in
cigarette smoke cause CYP1A2 induction
CYP1A2 is involved in generation of the
hepatic UROD inhibitor (uroporphomethene)
• Hepatitis C
– Reduces glutathione concentration in hepatic cells
 increasing oxidative stress in hepatocytes
– Increasing iron absorption by dysregulation of
hepcidin production by the liver
– Mutation in the HFE gene  increased intestinal
iron absorption

• HIV infection
– Mechanism not established
• Estrogens (OC, HRT)
– Mechanism unclear; estrogen undergo redox cycling and
cause oxidative damage in the kidney
• Chemical exposure
– Hexachlorobenzene, tetrachlorodibenzo-p-dioxin (TCDD)
• ESRD
– In pts on hemodialysis or peritoneal dialysis with iron
overload
• Other associations (weak)
– SLE, DM, hepatic steatosis

Diagnosis
• Blistering skin lesions on the backs of the hands
and other sun exposed areas of skin should suggest
the diagnosis of PCT
• It is essential to confirm the diagnosis of PCT
biochemically, because identical skin lesions can
be seen in a number of other porphyrias
– Variegate porphyria (VP)
– Hereditary coproporphyria (HCP)
– Pseudoporphyria

PCT is supported by demonstrating
• A marked increase in porphyrins in plasma and/or
urine
– Predominance of uroporphyrin and heptacarboxyl
porphyrins
– Urinary delta-ALA may be modestly increased, but
porphobilinogen excretion is normal
• Erythrocyte porphyrins are normal or modestly
increased in PCT
– In contrast, marked elevations in congenital
erythropoietic porphyria (CEP), hepatoerythropoietic
porphyria (HEP), and erythropoietic protoporphyria
(EPP)
• Total fecal porphyrins may be normal or
moderately increased with a complex pattern
including the presence of isocoproporphyrins

Other tests:
• Molecular studies are most accurate in
detecting UROD mutations in familial disease
• Patients should be evaluated for the presence
of susceptibility factors
• Liver findings (see some previous slide)

DDx
• CEP and HEP
– More severe blistering and scarring in CEP and HEP than in PCT
• EPP is nonblistering and cause immediate photosensitivity
• Other medical conditions (liver and bone marrow diseases)
– Elevations in urine porphyrins occur with coproporphyrin predomince
• Hereditary coproporphyria (HCP)
– Fecal porphyrins measurement needed to document as a cause of
coproporphyrinuria
• Variegate porphyria (VP)
– Show characteristic elevations in plasma and fecal porphyrins
• Cholestasis and renal failure
– Elevated plasma porphyrins
• Pseudoporphyria
– Skin lesions resembling PCT but without significant porphyrin
elevations
• Rare cases of primary hepatic tumors with cutaneous lesions10 August 2017 Porphyrias 65

Treatment
• Repeated phlebotomy
• Low-dose hydroxychloroquine is a suitable alternative
• Avoid exposure to sunlight by wearing protective clothing
• Oral analgesics for painful skin lesions
• Affected areas should be kept clean and skin infections
treated with antibiotics
• Patients are advised to avoid modifiable susceptibility
factors such as use of alcohol, smoking, estrogen therapy
(should be discontinued at least until remission is achieved)
• Drugs known to exacerbate acute porphyrias are seldom
reported to precipitate PCT

Repeated phlebotomy
• Remove one unit of whole blood (450 mL) at
intervals of approximately two weeks until the
serum ferritin is reduced to below approximately
20 ng/mL (near LLN)

Hydroxychloroquine or chloroquine
• A suitable alternative when phlebotomies are difficult or
poorly tolerated
• A low-dose regimen of hydroxychloroquine or chloroquine
is an effective treatment of PCT
• Mobilize porphyrins from the liver by a poorly defined
mechanism
• Dose: Hydroxychloroquine 100 mg orally twice weekly
– Retinopathy a potential dose-related risk
• Contraindications:
– Pregnancy, lactation, advanced liver disease, recent and
continued use of alcohol or hepatotoxic drugs (acetaminophen,
isoniazid or valproic acid), G6PD deficiency, psoriasis, and
retinal disease

Iron chelation
• Considered in rare instances when both
phlebotomy and low-dose hydroxychloroquine are
contraindicated
• Oral or subcutaneous iron chelators are much less
efficient in removing iron than phlebotomies

Other Rx options
• Thalidomide
• Plasmapheresis
• Vitamin E
• N-acetylcysteine
• Anastrazole
• Urinary alkalization
These should not be considered as alternatives to
phlebotomy or low-dose hydroxychloroquine

• Treatment of hepatitis C and HIV
• Genetic counseling

Hepatoerythropoietic porphyria

Introduction
• A rare autosomal recessive disorder
• Markedly reduced activity of hepatic
uroporphyrinogen decarboxylase (UROD)
• Homozygous or compound heterozygous form of
familial porphyria cutanea tarda
• Cutaneous photosensitivity usually begins in childhood
and is usually more severe than in PCT
• Disease onset is usually prior to two years of age,
although onset in adulthood has been reported
• The disease occurs worldwide and in both males and
females

PORPHYRIAS
hydroxymethylbilane
protoporphyrin IX
Heme
ALA synthase
ALA dehydratase
PBG deaminase
cosynthase
Uroporphyrinogen
decarboxylase
Coproporphyrinogen
oxidase
Protoporphyrinogen
oxidase
Ferrochelatase
ALA-dehydratase
Acute intermittent
porphyria
porphyria
Prophyria
cutanea tarda
Herediatary
coproporphyria
Variegate
porphyria
Erythropoietic
protoporphyria
Mitochondria

Pathogenesis
• HEP is due to markedly reduced activity of hepatic
uroporphyrinogen decarboxylase (UROD) to
usually < 20% of normal as measured in
erythrocytes
• Patients are either homozygous for one UROD
mutation or compound heterozygous for a different
UROD mutation inherited from each parent

• At least one of the inherited mutations must
express some UROD enzymatic activity, since a
null mutation would be lethal in the homozygous
state
• HEP is primarily hepatic
– Heme biosynthetic pathway in the bone marrow is also
affected  marked erythrocyte zinc protoporphyrin

Clinical features
• Skin photosensitivity is manifested early in life as
blistering, scarring, hypertrichosis and pigment
changes, resembling congenital erythropoietic
porphyria
• Clinical features in milder and later onset cases
may be indistinguishable from PCT
• Bacterial infections and scarring may be
disfiguring
• Mild hemolytic anemia may be accompanied by
hepatosplenomegaly

Diagnosis
• The possible presence of HEP should be considered in
children with chronic, blistering photosensitivity
• Porphyrin patterns in HEP closely resemble those seen
in PCT. However,
– A marked elevation in erythrocyte protoporphyrin
(mostly zinc protoporphyrin) is characteristic of HEP
– Porphyrin precursors are normal (ie, delta-ALA and
porphobilinogen)
• Hematological abnormalities
– Mild, normocytic normochromic anemia due hemolysis
• Abnormalities in liver function and histology but
without siderosis

Treatment
• Protection from sunlight is especially
important in patients with HEP and is the only
recognized treatment for this disorder.
– With such management, the overall prognosis is
good, but fingers and facial features may be
disfigured in severe cases
• Genetic counseling and prenatal diagnosis

References
• UpToDate Medicine 2013 Edition
• Medscape Online Edition
• Merck Manual Online Professional Edition
• Harrison Textbook of Internal Medicine 19th
Edition, 2015
• Rook’s Textbook of Dermatology

Porphyria by Dr. Basil Tumaini

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