PEDBASE.org - The Pediatric Database - Detailed information of ACUTE INTERMITTENT PORPHYRIA

ACUTE INTERMITTENT PORPHYRIA

DEFINITION:

An autosomal dominant disorder of heme synthesis characterized primarily by gastrointestinal and neurological complaints.

EPIDEMIOLOGY:

incidence: 5-10/100,000
age of onset:
- after puberty
risk factors:
- familial - autosomal dominant
  - chrom. #: 11q24.1-q24.2
  - gene: porphobilinogen (PBG) deaminase
- higher incidence in psychiatric populations
- F > M

PATHOGENESIS:

1. Background

majority (90%) latent with clinical expression when exposed to triggering factors:

1. Nutritional Status

decreased caloric (carbohydrate) intake

2. Drugs

barbiturates, sulfonamides, ergots, griseofulvin, diphenylhydantoin, chlordiazepoxide

3. Hormones

sex steroid metabolites (progesterone, synthetic estrogens)

4. Stress

alcohol excess, infections, surgery

full clinical expression occurs with exposure to triggers which activate the disease primarily by inducing ALA synthetase in the liver resulting in excess production of ALA and PBG (a trigger may be any factor which increases heme synthesis)

2. Genetic Defect

at least 27 mutations have been isolated so far in the PBG deaminase gene (Gu, X., et al. Human Genetics 93:47-52 [1994])

CLINICAL FEATURES:

1. Gastrointestinal Manifestations

abdominal pain (91%)
vomiting (63%)
constipation (60%)
diarrhea (9%)
others - distension, ileus

2. Neurologic Manifestations

1. Motor

muscle weakness (57%)
acute ataxia
bulbar paralysis
cranial nerve palsies (7th, 10th)
decreased deep tendon reflexes

2. Sensory

loss (24%)
pain (51%) - head, neck, chest, limbs
others- paresthesia, numbness, dysesthesia, ocular blindness

3. Autonomic

increased sympathetic outflow
- tachycardia (57%)
- hypertension (43%)
- fever (20%)
- others - hypotension, urinary retention, sweating, nausea/vomiting, constipation, diarrhea, restlessness, tremor

4. Seizures (15%)

3. Psychiatric Manifestations (51%)

anxiety
depression
hallucinations
hysteria
insomnia, paranoia
paranoia
restlessness
violence

4. Respiratory (11%)

respiratory paralysis

5. Renal

SIADH, chronic renal failure

INVESTIGATIONS:

1. Urinalysis

"port-wine" urine (PBG -> porphobilin)
brown pigments
porphyrin and porphobilinogen screens and if positive then quantitative ALA, PBG, and porphyrins (which should be increased)

2. Serum

increased ALA, PBG
hypercholesterolemia

3. Diagnosis

deficiency of PBG deaminase (50% of normal) activity in erythrocytes

MANAGEMENT:

1. Prophylaxis

avoid triggering factors

2. Acute Episodes

1. Nutritional

increase carbohydrate (CHO) intake:
- supplemental Polycose
- D10W (minimum of 300 g CHO/day)

2. ATI/Neuropathies

intravenous hematin
- side effects: phlebitis, thrombophlebitis, coagulopathy, hemolysis, hypotension, acute renal failure
others: haem-arginate Sn-protoporphyrin hemoperfusion

3. SIADH

fluid restriction
hypertonic saline

4. Pain

frequent doses of narcotic analgesia

5. Psychiatric Problems

phenothiazines, chloral hydrate

6. Increased Sympathetic Output

propranolol

Pediatric Database - ACUTE INTERMITTENT PORPHYRIA

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