400
CASE FILES: BIOCHEMISTRY
A N SW E R S TO C A SE 44: P O R P H Y R IA (A C U T E
IN T E R M IT T E N T P O R P H Y R IA )
Summary:
A 21-year-old healthy male patient with sudden onset abdominal
pain, nausea and vomiting, hypertension, tachycardia, and peripheral neuropa-
thy after consumption of first alcoholic beverage. Further testing revealed ele-
vated levels of both serum and urine ALA and PBG.
Diagnosis: Porphyria (likely acute intermittent porphyria, i.e., variegate)
Biochemical problem: Enzymatic deficiency in heme biosynthetic
pathway
C L IN IC A L C O R R E L A T IO N
Porphyrias are inherited disorders in the heme biosynthetic pathway. Porphyrias
are classified as either hepatic or erythropoetic depending on primary site of
accumulation. Inheritance is usually autosomal dominate. Patients often are
asymptomatic unless exposed to factors that increase production of porphyrias
(drugs, alcohol, sunlight). Erythropoetic etiologies primarily present with pho-
tosensitivity. Hepatic porphyrias present with primarily neurovisceral symptoms
such as: abdominal pain, nausea and vomiting, tachycardia and hypertension,
peripheral neuropathy, and mental symptoms (hallucinations, anxiety, seizures).
Diagnosis is confirmed with elevated levels of ALA and PBG in the urine and
serum. Specific tests can be performed to detect which enzyme is deficient (i.e.,
variegate porphyria is caused by deficiency in the PPO enzyme). Treatment is
supportive with avoidance of triggers in the future.
O bjectives
1.
Describe the biosynthesis of heme.
2.
Explain why certain triggers (such as EtOH) cause an increase in ALA
and PBG.
3.
Explain why treatment with intravenous heme or hematin is effective.
D efinitions
Aminolevulinic acid synthase (ALAS): Mitochondrial matrix enzyme that
catalyzes the rate-limiting synthesis of ALA via condensation of
succinyl-CoA and glycine.
ALA dehydratase (ALAD): Cytosolic enzyme that catalyzes the asym-
metric condensation of two molecules of ALA to form PBG.
Autonomic neuropathy: Autonomic nervous disruption or deregulation
affecting the cardiovascular, urogenital, gastrointestinal systems; symp-
toms include abdominal pain, nausea and vomiting, tachycardia and
hypertension; (aka visceral neuropathy).
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