Acute hepatic porphyrias for the neurologist: current concepts and perspectives.

Paulo Victor Sgobbi De Souza,Wladimir Bocca Vieira De Rezende Pinto,Eduardo Augusto Gonçalves,Acary Souza Bulle Oliveira,Bruno De Mattos Lombardi Badia,Igor Braga Farias

doi:10.1590/0004-282x20200096

Paulo Victor Sgobbi De Souza, Wladimir Bocca Vieira De Rezende Pinto + Show 4 more

Open Access

https://doi.org/10.1590/0004-282x20200096

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Abstract

Acute hepatic porphyrias represent an expanding group of complex inherited metabolic disorders due to inborn errors of metabolism involving heme biosynthesis. We aimed to review the main clinical and therapeutic aspects associated with acute hepatic porphyrias. The authors provided a wide non-systematic review of current concepts and recently acquired knowledge about acute hepatic porphyrias. Acute neurovisceral attacks are the most common and life-threatening presentation of this group and are often considered the main clinical manifestation by clinicians during differential diagnosis and the start of proper diagnostic work-up for acute porphyrias. However, atypical presentations with central nervous system involvement, neuropsychiatric disturbances, and some subtypes with photosensitivity usually make the definite diagnosis difficult and late. Early therapeutic interventions are essential during emergency treatment and intercritical periods to avoid recurrent severe presentations. The availability of new disease-modifying therapeutic proposals based on small interfering RNA (siRNA)-based therapies, complementary to the classic intravenous glucose infusion and hemin-based treatments, emphasizes the importance of early diagnosis and genetic counseling of patients. This review article highlights the main biochemical, pathophysiological, clinical, and therapeutic aspects of acute hepatic porphyrias in clinical practice.

Highlights

Porphyrias are rare inherited metabolic disorders of the heme biosynthesis pathway, leading to the pathogenic accumulation of heme precursors and porphyrins
Porphyrias are divided according to two main categories: (i) the site of main overproduction of porphyrin precursors, including hepatic and erythropoietic porphyrias; and (ii) type of clinical presentation, including acute and chronic porphyrias[1,2,3]
We present data from the Drug Database for Acute Porphyria, which is annually updated by the UK Porphyria Medicines Information Service (UKPMIS), the Cardiff Porphyria Service, and the National Acute Porphyria Service (NAPS) (Table 4)[6,22]

Summary

INTRODUCTION

Porphyrias ( from the Greek Porphyrus, purple) are rare inherited metabolic disorders of the heme biosynthesis pathway, leading to the pathogenic accumulation of heme precursors (i.e., porphobilinogen and delta-aminolevulinic acid) and porphyrins. 1. Acute or subacute-onset flaccid paralysis (proximal and upper limb-dominant weakness) in the ED/ICU, especially in case of: (i) prior chronic or subacute history of behavioral or neuropsychiatric changes (i.e., mood or psychotic changes); (ii) moderate to severe hyponatremia; (iii) severe dysautonomic changes (i.e., usually pandysautonomia in the ICU); (iv) severe abdominal pain with/without dark urine; (v) blistering skin changes involving hands or face; (vi) positive family history of AHP cases or possible diagnosis; (vii) normal CSF analysis; (viii) positive history of exposure to potentially porphyrinogenic precipitants (i.e., drugs, chronic lead poisoning, premenstrual period). Differential diagnosis of AHPs during acute neurovisceral attacks and chronic presentation

Dark-reddish urine

Skin lesions

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CONCLUSIONS