[Porphyrias and haem related disorders]

Area of Science:

• Biochemistry
• Genetics
• Metabolic Disorders

Background:

• Hereditary porphyrias are a group of eight distinct metabolic disorders affecting the haem biosynthesis pathway.
• These conditions result from specific enzymatic defects, leading to the accumulation of haem precursors.
• Porphyrias manifest with diverse clinical presentations, including acute neurovisceral crises and cutaneous lesions.

Purpose of the Study:

• To provide an overview of the hereditary porphyrias, encompassing their genetic basis, clinical manifestations, and diagnostic approaches.
• To highlight the importance of early diagnosis and family screening for effective management and prevention of complications.

Main Methods:

• Review of the pathophysiology of eight distinct hereditary porphyrias.
• Description of clinical presentations, ranging from acute neurovisceral symptoms to cutaneous manifestations.
• Emphasis on diagnostic strategies, including front-line testing for symptomatic individuals and presymptomatic carrier screening.

Main Results:

• Seven porphyrias result from partial enzyme deficiencies, while one novel porphyria involves a gain-of-function mechanism.
• Acute porphyrias present with life-threatening neurovisceral symptoms; cutaneous porphyrias exhibit photosensitivity or blistering.
• Rare recessive forms manifest in childhood with severe neurological or hematological issues and skin fragility.

Conclusions:

• Porphyrias remain underdiagnosed, necessitating increased awareness and prompt diagnostic evaluation.
• Accurate diagnosis enables timely initiation of specific treatments to manage symptoms and prevent disease progression.
• Family screening is vital for identifying presymptomatic carriers, allowing for counseling on precipitating factors and preventing chronic complications.