PORPHYRIA

Heme, composed of ferrous iron and protoporphyrins, is an essential constituent of hemoglobin, myoglobin and many other enzymes. The porphyrias are inherited disorders of heme biosynthesis due to various enzyme defects (Fig.

Porphyrias are classified according to the order of defective enzyme in heme biosynthesis (Table 11.18) or the site of expression, i.e. acute hepatic porphyrias (ADP, AIP, HCP, VP) or erythrocytic porphyrias (CEP, PCT, HEP, EPP). Of these, most common are acute intermittent porphyria, porphyria cutaneous tarda and erythrocytic porphyria, discussed here in greater details.

Acute intermittent porphyria (AIP), is the commonest genetic porphyria, which usually presents beyond puberty.

Clinically, it present with acute episodes of: (a) severe abdominal pain with/without vomiting, mimicking surgical abdomen, (b) neuropathy with proximal muscle weakness and cranial nerve involvements, and (c) cardiovascular signs, e.g. tachycardia with hypertension,

Fig. 11.11: Important steps in heme synthesis and enzymatic origin of various porphyrias.

which may persist even after the episode. Attacks are precipitated by fasting, infections, surgery, drugs/ chemical ingestion or hormonal factors, e.g. menses in females. Skin manifestations are absent.

Diagnosis rests on decreased porphobilinogen deami­nase activity in erythrocytes, though elevated levels of porphobilinogen in urine on Watson-Schwartz screening test or chromatographic studies are highly suggestive.

Treatment is largely supportive during the attack, which may be prevented by adequate caloric intake, avoidance of precipitant drugs and prompt management of infections. IV hematin (4 mg / kg / BD) may curtail severe attacks.

Porphyria cutanea tarda (PCT), the commonest por­phyria, which may be inherited (autosomal dominant) or acquired. Acquired PCT is mainly seen in adults after exposure to factors, e.g. alcohol, estrogens or drugs.

Clinically, cutaneous photosensitivity with formation of vesicles over exposed parts of body is pathognomonic of PCT, which may heal with crusting, scarring and residual pigmentation. Neurological or visceral mani­festation are absent.

Diagnosis rests on elevated excretion of urinary and fecal porphyrins, specially isocoproporphyrin levels in stools. Daily porphyrin excretion in stools exceeds that in urine.

(EPP)

AP: Abdominal pain, HA: Hemolytic anemia, MOI: Modes of inheritance

Treatment is symptomatic, though avoidance of sunlight and precipitating factors in acquired disease is necessary.

Erythrocytic protoporphyria (EPP), an autosomal dominant ferrochelatase deficiency, typically manifests in childhood, with extreme cutaneous photosensitivity. Clinically, EPP present with stingy or burning sen­sations within 1-2 hours of sun exposure followed by erythema and edema. Vesicles are less common but repeated attacks lead to hyperkeratosis of exposed skin and onycholysis. Chronic hepatic disease and gallstones are common. Neuro-visceral involvement is absent.

Diagnosis rests on elevated free protoporphyrin levels in erythrocytes, plasma and stools, with normal urinary porphyrins.

Treatment includes avoidance of sun-exposure and use of topical sunscreen agents to prevent skin burning. Oral administration of #946;-carotene increases photo-tolerance to some extent.

BIBLIOGRAPHY

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