Porphyria metabolic abnormalities

Several behavioral disturbances Including psychoses frequently accompany Hartnup s disease, Wilson s disease, porphyria and pellagra, diseases in which Indoleamine abnormalities have been identified.100 These behavioral aberrations generally recede during clinical remission of the primary metabolic abnormality. 

Inborn metabolic diseases that interfere with heme biosynthesis are called porphyrias. Porphyrias have a variety of symptoms. A deficiency in the enzyme responsible for the condensation of porphobilinogen to the 4-membered ring system leads to a condition called acute intermittent porphyria, which is characterized by occasional episodes of abdominal pain and psychiatric symptoms. Defects in the later enzymes of the pathway lead to an excess accumulation of the uroporphobilinogens in the tissues, where they cause a variety of symptoms, including hairy skin, skeletal abnormalities, light sensitivity, and red urine. Individuals with this disease are still anemic—a condition that can be alleviated somewhat by the heme acquired from drinking blood. This combination of traits sounds like the werewolf and vampire legends of Europe, which may have their base in this rare biochemical disease. 

Pseudoporphyria is a photodistributed bullous disorder with clinical and histological features similar to those of porphyria cutanea tarda, but without accompanying abnormalities of porphyrin metabolism. Drugs, in particular NSAIDs and sulfur-containing diuretics, often cause pseudoporphyria (193). Pseudoporphyria associated with naproxen (15 mg/kg/day) has been reported in a child (194). 

Abnormalities of porphyrin metabolism are caused by inherited defects in the genes of the biosynthetic pathway enzymes, diseases called the porphyrias, or by conditions (e.g., lead toxicity) that affect the enzymatic activity in subjects with normal heme synthesis genes. 

Abnormalities of porphyrin metabolism, excretion, or both may occur in the absence of porphyria caused by a number of other diseases that need to be considered when interpreting data from patients in whom porphyria is suspected. ... 

McCoU KEL, Godberg A. Abnormal porphyrin metabolism in diseases other than porphyria. Clinics in Haematology 1980 9 427-45. 

The basic concept upon which ALA-PDT is based was conceived as we studied the biochemical basis for the group of metabolic diseases known as the porphyrias [43]. Some of the porphyrias are associated with a generalized photosensitization which is caused by the accumulation of specific types of porphyrin in the blood and/or tissues, where each type of porphyrin accumulates as the result of a specific abnormality in the biosynthetic pathway for heme. Although at that time it was generally believed that the expression of such abnormalities was restricted to the liver and the hemopoietic system (those tissues which synthesize large amounts of heme), it was obvious that all nucleated cells must have at least some capacity to synthesize heme because they all use heme-containing enzymes for the tricarboxylic acid cycle. 

The porphyrias are a group of diseases in which disturbances of porphyrin metabolism occur either as inherited or acquired abnormalities. They are classified into the so-called erythropoietic and hepatic forms according to the chemical evidence of the primary site of the metabolic defect [63], and it is the second, hepatic group which mainly concerns us here in this discussion on neuropathies. 

With the recognition that there is abnormal excretion of certain porphyrins in the hereditary porphyrias it was assumed that as in other metabolic errors, the abnormalities resulted from an enzyme block either in an associated pathway diverting more substrate to porphyrin synthesis or in porphyrin utilization leading to an accumulation of metabolic precursors. However, further observations showed that neither of these hypotheses was tenable. 

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