Porphyrias are caused by enzymatic defects in the heme pathway. There are several forms, each with similar neurological findings, highlighted by abdominal pains and peripheral neuropathy. Those with autosomal dominant inheritance include acute intermittent porphyria (AIP), due to porphobilinogen deaminase deficiency, hereditary coproporphyria (HCP) due to coproporphyrinogen oxidase deficiency, and variegate porphyria (VP), due to protoporphyrinogen oxidase deficiency. An autosomal recessive condition characterized by deficiency in delta-aminolevulinic acid dehydratase has been described.

In AIP, although the enzymatic defect is constant throughout life, neuropathic crises are interspersed between long periods of near-normal function. Abdominal pain usually is the initial symptom of a neuropathic attack, followed by a subacute motor neuropathy that may ascend from the feet, resembling Guillain-Barre syndrome. Facial, bulbar, and extremity weakness develops in most cases. Electromyographic studies help in distinguishing AIP from demyelinating neuropathy, since in the former, denervation and evidence of axonal neuropathy is more pronounced than slowed conduction velocities. In addition to these typical neuropathic signs, dysautonomia may be pronounced and lead to cardiac arrhythmias, blood pressure instability, and urinary retention. Neurobehavioral signs indicative of CNS involvement include psychotic behavior, delirium, and seizures, although the seizures are usually due to hyponatremia and inappropriate release of antidiuretic hormone.[75]

Although the crises of AIP may be spontaneous in onset, certain risk factors are identified, including infection, ingestion of alcohol, and use of a large variety of drugs, including anticonvulsant medications. The diagnosis of AIP depends on the clinical presentation of intermittent painful crises, behavioral alterations, and neuropathy with excessive urinary excretion rates of delta-aminolevulinic acid and porphobilinogen. Treatment involves special dietary changes at the earliest sign of an attack. Patients must immediately increase their carbohydrate intake; and if this maneuver does not abort the crisis, intravenous dextrose and hematin should be given to prevent activation of hepatic delta- aminolevulinic acid synthetase. In light of the large number of drugs associated with exacerbation of AIP crises, the control of the painful abdominal cramps is problematic, although low-dose narcotics may be used in many patients, sometimes supplemented with very low doses of benzodiazepine derivatives.^

HCP is much rarer than AIP. The neuropathic and systemic clinical manifestations of the two conditions are the same, except that a distinctive cutaneous photosensitivity occurs in one third of the HCP patients. Like AIP, HCP is punctuated with crises of neurological dysfunction that are precipitated by drugs, infections, and alcohol. HCP has a characteristic metabolic profile with elevated urinary and fecal coproporphyrins. Similar to AIP, delta-aminolevulinic acid and porphobilinogen are found in the urine but also found is coproporphyrin, a product not found in AIP. Enzyme assays for coproporphyrin oxidase will demonstrate the deficiency, but this test is not readily available. y

VP is particularly found in southern Africa. It mimics AIP and CHP clinically, and photosensitivity is common. [76] In addition, a variety of skin lesions, including hyperpigmentation, hypertrichosis, vesicles, and bullae, are seen in patients with VP. Excretion patterns are similar to those of HCP, except the excreted amount of porphobilinogen exceeds coproporphyrin in VP whereas they are approximately equal in HCP. Treatment is the same as for AIP and HCP.

Finally, delta-aminolevulinic acid dehydratase deficiency is unique in being an autosomal recessive disorder. Neurological findings, as well as systemic and dermatological signs, mimic those of the other porphyrias, and the differentiation is made exclusively on the biochemical findings of enzyme deficiency and the high urinary excretion of delta-aminolevulinic acid without porphobilinogen. bi


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Peripheral Neuropathy Natural Treatment Options

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