Patient is a fourteen year old boy who is a known case of porphyria. He presented with weakness of the right upper extremity, seizures and abdominal cramps.
There are hyperintense areas on the Proton, T2W and FLAIR images along the cortex and subcortical white matter in the left fronto-parieto-temporal lobes and in the right centrum semiovale. These are hypointense on the T1W images. Similar signal changes are seen in the lentiform and caudate nuclei, bilaterally, in a symmetric fashion. These changes would be most likely ischemic in etiology.
Porphyria is a group of at least eight disorders that differ considerably from each other. A common feature in all is the accumulation in the body of "porphyrins" or "porphyrin precursors". Though normal body chemicals, they normally do not accumulate. Which of these chemicals builds up depends upon the type of porphyria. The symptoms arise mostly from effects on the nervous system or the skin. Effects on the nervous system occur in the acute porphyrias. Skin manifestations can include burning, blistering and scarring of sun-exposed areas. The terms "porphyrin" and "porphyria" are derived from the Greek word "porphyrus" meaning purple. Urine from some porphyria patients may be reddish in color due to the presence of excess porphyrins and related substances, and the urine may darken after standing in light.
In each type of porphyria there is a deficiency of a specific "enzyme". These enzymes are involved in the synthesis of heme (found in largest amounts in the bone marrow, red blood cells and the liver). Heme exists as hemoglobin in the bone marrow and red blood cells but has other functions in other tissues such as the liver. The type of porphyria present is determined by which enzyme is deficient. These enzyme deficiencies are usually inherited. The different type of porphyrias are as follows:
Sometimes, other classifications are useful. For example, the porphyrias are often divided into two groups, the "hepatic" and "erythropoietic" types. Porphyrias with skin manifestations are sometimes called "cutaneous porphyrias". The "acute porphyrias" are those characterized by attacks of pain and other neurological manifestations. These "acute" symptoms can be both rapidly-appearing and severe. An individual may be considered "latent" if he or she has the required enzyme deficiency but has never developed symptoms.
Acute Intermittent Porphyria (AIP)
This is one of the hereditary hepatic porphyrias. Its inheritance is autosomal dominant. The deficient enzyme is porphobilinogen deaminase
(PBGD). A deficiency of PBGD is not sufficient by itself to produce AIP, and other activating factors must also be present. These include hormones, drugs and dietary changes.
Symptoms:
AIP manifests after puberty, especially in women due to hormonal influences. Symptoms usually occur as attacks that develop over several hours or days. Abdominal pain, which can be severe, is the most common symptom. Others may include nausea, vomiting, constipation, pain in the back, arms and legs, muscle weakness (due to effects on nerves supplying the muscles), urinary retention, palpitation (due to a rapid heart rate and often accompanied by increased blood pressure), confusion, hallucinations and seizures. Patients with AIP
may present with neurological syndromes such as autonomic neuropathy, peripheral axonal
neuropathy or central nervous system dysfunction. Sometimes the level of salt (sodium and chloride) in the blood decreases markedly and contributes to some of these symptoms.
Diagnosis:
The finding of increased levels of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) in urine establishes that one of the acute porphyrias is present. If PBGD is deficient in normal red blood cells then the diagnosis of AIP is established. However, measuring PBGD in red blood cells should not be relied upon by itself to exclude AIP in a sick patient, because the enzyme is not deficient in red blood cells of all AIP patients.
On MRI: |
Magnetic resonance imaging in patients who have neurological symptoms may show cerebral abnormalities consistent with ischemic brain lesions. Multifocal ischemia and cerebral microinfarctions, possibly resulting from porphyria-induced vasospasms, may be important causes of cerebral dysfunction during acute attacks of acute intermittent porphyria. MRI may show central pontine and extrapontine myelinolysis and/or cortical laminar necrosis. These are not common in AIP, but may be due to rapid correction of hyponatraemia and by vasospasm, which could be induced by AIP. Some of these lesions may resolve and have a picture similar to that seen with posterior leukoencephalopathy syndromes.
However, the pathogenesis of the suspected cerebral vasoconstriction in acute intermittent porphyria is unknown. Possibly the activity of the enzyme nitric oxide synthase may be reduced in situations of decreased heme production such as acute intermittent porphyria. Nitric oxide is an important vasodilator in the central nervous system and decreased cerebral nitric oxide production in patients with acute intermittent porphyria may lead to unopposed cerebral vasoconstriction, potentially leading to lesions in areas of the brain that are particularly vulnerable to hypoxia.
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