2. Vampire disease
Rare disorders of heme metabolism
Characterized by defect in enzyme required
for synthesis of heme.
Can cause pathology of multiple organ
systems-neurologic (central and/or
peripheral), dermatologic and gastrointestinal
6. Most common porphyria
Sporadic(type I) or familial (type II)
Autosomal dominant
Hepatic URO-decarboxylase activity must be
20% of normal or less.
Clinical features
Blistering skin lesions, most commonly on
backs of hands
7. Rupture and crust over, leaving areas of
atrophy and scarring.
Can be on forearms, face, legs, and feet.
Skin friability and small white papules termed
milia
Hypertrichosis and hyperpigmentation
Sunexposed Skin areas becomes severely
thickened with scarring and calcification-
resembles systemic sclerosis.
Neurologic features are absent.
9. Treatment
Repeated phlebotomy- a unit of blood
removed approximately every 2 weeks.
Serum ferritin-25 ng/mL
Low-dose regimen of chloroquine or
hydroxychloroquine
◦ 125 mg chloroquine phosphate twice weekly
◦ Mobilizes excess porphyrins from liver and
promotes their excretion
10. Congenital erythropoietic porphyria (CEP)
◦ Autosomal recessive
◦ URO-synthase
◦ Non immune hydrops fetalis
◦ Severe cutaneous photosensitivity
◦ Skin friable, bullae and vesicles->rupture, infection
◦ Skin thickening, focal hypopigmentation and
hyperpigmentation
◦ Teeth-reddish brown, fluoresce on exposure to
long-wave ultraviolet light.
◦ Hemolysis, splenomegaly
11. Diagnosis
◦ Uroporphyrin and coproporphyrin (mostly type I
isomers) in bone marrow, circulating erythrocytes,
plasma, urine, feces.
◦ Demonstration of markedly deficient URO-synthase
activity or specific mutations in UROS gene
Treatment-
◦ Chronic erythrocyte transfusions
◦ Bone marrow/ cord blood transfusion
12. EPP and XLP
◦ EPP -autosomal recessive disorder, FECH gene
◦ X-linked form of EPP, XLP-gain-of-function
mutations in last exon of ALAS2 gene
◦ Skin photosensitivity-usually begins in early
childhood and consists of pain, redness, and itching
occurring within minutes of sunlight exposure
◦ Secondary lichenification
◦ Hemolysis
◦ Liver damage
15. Typically occur after puberty.
0.5–10 per 100000 people
Scandinavia, Britain, Ireland,Sweden-AIP
White South African-VP
Approximately 50% reduction in affected
enzyme for their respective disorders
W198X mutation-AIP
I12T mutation-VP
16. Characterized by relatively quiescent phases
interspersed with attacks of disease
Often precipitated by drug or toxin exposure
or hormonal changes
Not fully penetrant
Less than 10% carrying mutation become
symptomatic throughout their life
Increased risk of cancer
19. Polymorphic
5-17% of symptomatic patients-neurological
impairment
Mortality of acute attack high (~10%)
Correct diagnosis and treatment at early
phase of acute attack crucial to prevent
progression.
20. Responsible for majority of symptoms during
acute attack
Abdominal pain-hallmark of acute attack
Exact mechanism of pain-obscure
Splanchnic dysfunction-intestinal dilatation
or spasm
Alternative mechanisms such as local
vasoconstriction and intestinal ischemia
Enteric ganglionitis/ganglionopathy or
sensory neuropathy
21. Tachycardia-reflects activity of disease
Commonly associated with pain
In combination with constipation,
hypertension, bladder paresis.
Orthostatic hypotension, diastolic
hypertension and diarrhoea
Abnormal parasympathetic cardiac reflexes
22. Vagus nerve demyelination, axonal loss and
chromatolysis of sympathetic ganglion cell in
autopsies
Direct gut-spasmodic effect of ALA
Vagal insufficiency
23. Most common neurological complication-
severe acute attack
Occurs later, within a few days or so of
symptom onset.
Typically motor predominant, asymmetric
Weakness-evenly distributed in proximal and
distal muscle groups of upper extremities.
Lower extremities-weakness more in
proximal muscles
Symmetrically distributed hyporeflexia,
weakness and sensory loss
24. Preservation of ankle jerks- 50%
Respiratory failure-diaphragm paresis-10% to
64%
Uncommon if treated at early phase of acute
attack
Sensory -painful paresthesia, hyperesthesia
Sensory loss-less common
Glove-and-stocking distribution or patchy
proximal
Cranial neuropathy-III, VI, IX and X in 35-55%
25. Axonal-more common
Demyelinating seen in more severe.
Nerve biopsy- axonal as well as
demyelinating
CSF examination- usually normal
Single case-mononeuritis multiplex, focal
motor polyneuropathy, "pseudo myasthenia"
during an acute attack-published
3 cases of rhabdomyolysis published
26. Combination of headache, altered
consciousness and behaviour or seizures
Can be visualized as posterior reversible
encephalopathy syndrome (PRES) in
neuroimaging
Suggests breakage of blood-brain barrier-
which permits access of neurotoxins such as
ALA to neurons.
Theory of endothelial toxicity-main cause of
vasogenic oedema in AIP
Hypertension acts as a co-factor for PRES
27. Generalised or focal epileptic seizures-2% to
20%
Mild to moderate hyponatraemia in absence
of loss of sodium due to diarrhea, vomiting
or polyuria-SIADH-25-61 %
Transient cortical blindness, hemianospia,
cerebellar ataxia, parkinsonism, finger
tremor, dysphasia, central pontine
myelinolysis- single case
CSF during acute attack-normal
28. Mild mental symptoms-anxiety, insomnia are
usually present at beginning of acute attack
even before abdominal pain.
Mental syndrome of acute porphyria-Aberrant
behavior, pyschosis, hallucinations-19% -56%
Anxiety commoner among AIP patients than
general population
29.
30. Haem-synthesized in every human aerobic
cell, mainly in erythroid cells and liver
Activation of ALA synthase (ALAS1) in liver-
rate limiting enzyme
ALAS1-negative feedback by haem
Accumulation of porphyrins and their
precursors
Haem also synthesised locally in brain
Role of intra-neural synthesis in neurological
manifestations-unclear.
31. ALAS1-induced directly at transcriptional and
translational level by many drugs, chemicals
and alcohol or indirectly by low glucose
concentration and stress. the end-product of
the biosynthesis (25).
Glucose inhibits ALAS1 indirectly-
peroxisome-proliferator-activated receptor γ
coactivator 1α (PCG-1α)
32.
33. Peripheral nervous system
Axonal degeneration and patchy demyelination
of motor axons, particularly short motor axons.
Axons-thin and irregular, with vacuolization,
degeneration, cellular infiltration.
Neuronal loss and chromatolysis of anterior horn
cells-secondary to retrograde degeneration.
Chromatolysis of cranial nerve nuclei, commonly
dorsal vagus nucleus and autonomic nervous
system ganglia (eg, celiac ganglion)
34. CNS
Chromatolysis and vacuolization of neurons
Selective involvement of oligodendrocytes.
Focal perivascular demyelination, reactive
gliosis in supraoptic and paraventricular
nuclei of hypothalamus.
35.
36. High clinical suspicion.
Presence of a family history of similar
symptoms
History of discolored urine
Measurement of porphyrin levels in urine,
stool, and blood;
In AIP-elevated urinary excretion of
aminolevulinic acid (ALA), porphobilinogen
(PBG), uroporphyrin, and coproporphyrin;
Erythrocyte PBG deaminase may be normal or
decreased.
37. In asymptomatic phase, in between attacks-
decreased erythrocyte PBG deaminase or
value can be normal
Hereditary coproporphyria-urine
coproporphyrin, ALA, uroporphyrin, PBG
levels and fecal coproporphyrin level-
increased during attack
Coproporphyrin-increased in urine and feces
in between attacks as well.
38. Variegate porphyria-increased levels of urine
and fecal porphyrins during attack
Latent phase-increased coproporphyrin.
Falsely increased porphyrins- medication
inducing cytochrome 450
DNA testing-AIP, hereditary coproporphyria
and variegate porphyria
39. Hoesch test
Mix 1-2 drops of urine with 1 mL of 6-mol/L
hydrochloric acid (HCl) and 20 mg of para-
dimethylaminobenzaldehyde(DMAB).
Immediate development of a cherry-red color
at top of mixture-positive result.
40. Watson-Schwartz test
Mix 7.5 mL of a DMAB solution (10 mg/mL HCl)
with 5 mL water.
Mix 1 mL of solution with 1 mL urine.
Immediate formation of a red color-PBG excess.
Confirmed by adding 2 mL saturated sodium
acetate and then 3 mL chloroform to the positive
mixture.
After vigorous shaking, red upper aqueous phase
and pink lower organic solution phase-positive
result.
41. AIDP
◦ Lack of central nervous system manifestations such as
seizures or psychiatric symptoms
◦ Primary demyelinating features on nerve conduction
Multifocal motor neuropathy
CIDP
POEMS (polyneuropathy, organomegaly,
endocrinopathy, M-protein, skin changes)
Lyme disease, West Nile virus, enterovirus,
herpesvirus-mediated polyradiculo-neuropathies
Vasculitic neuropathies.
Lead neuropathy
42. Avoidance of cytochrome P 450 inducing
agents
Avoidance of alcohol
Avoid prolonged fasting
Intravenous hematin
◦ Inhibits heme synthesis in liver.
◦ Heme arginate, heme albumin
◦ Daily dose of 2–5 mg/kg given for 3–14 days
◦ Side effects-renal failure, phlebitis, and
coagulopathy
43. Intravenous glucose supplementation is
◦ 3–500 g intravenously per 24 hours
Liver transplantation
Antiepileptics
◦ Phenytoin, phenobarbital, valproic acid-
contraindicated
◦ Clonazepam- controversial
◦ Leviteracetam
◦ Vigabatrin and Gabapentin
◦ Intravenous magnesium
44. Attack of acute hepatic porphyric-good
Rapid resolution of abdominal pain,
autonomic symptoms, and central nervous
system manifestations once attack is aborted.
Neuropathy resolves much more slowly
Recovery depends on extent and magnitude
of axonal degeneration.
Usually occurs over many months, often
incomplete
Repeated attacks-cumulative deficits occur
48. Porphyria and its neurologic manifestations; Jennifer
A. Tracy And P. James B. Dyck; Neurologic Aspects of
Systemic Disease Part II; 2014 Elsevier B.V.
Neurological Manifestations Of Acute Intermittent
Porphyria;Pischik E.;Cellular And Molecular
Biology;2012
The porphyrias: advances in diagnosis and treatment;
Manisha Balwani1 and Robert J. Desnick: Blood, 29
November 2012 Volume 120, Number 23
Acute intermittent porphyria presenting with
neurological emergency: Review of six
cases:Neurology India | October-December 2007 |
Vol 55 | Issue 4
Porphyric Neuropathy;james W. Albers, John K. FINK;
Muscle Nerve 30: 410–422, 2004
