Porphyrias
Porphyrias are disorders of haem synthesis resulting in rapid quadriparesis, autonomic dysfunction, psychiatric manifestations and abdominal pains, forming a close differential diagnosis to Guillain–Barré syndrome. Rapid therapy with glucose and intraveno
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43.1 Introduction Porphyrias are a group of inherited metabolic disorders of haem synthesis (Lancet 2010). Enzyme defects in the haem biosynthesis pathway result in the accumulation of haem precursors, e.g. aminolevulinic acid (ALA), porphobilinogen (PBG) and porphyrins. These disorders can present as acute neuro-visceral syndromes, skin lesions or both. Porphyrias are largely transmitted as autosomal dominant disease but, uncommonly, can be recessive. Based on clinical presentation, porphyrias can be classified into acute porphyrias and cutaneous porphyrias. Acute porphyrias present with life-threatening crisis and are most frequently encountered by neurologists. Porphyrias often present with acute quadriparesis, autonomic dysfunction, sensory complaints, abdominal pain and neuropsychiatric manifestations. It is important to screen for porphyrias as delay in treatment can be fatal. This chapter will cover information about porphyrias that present with neurological features (Puy et al. 2010; Solinas and Vajda 2008; Sylantiev et al. 2005). Subtypes of porphyrias that can present with neurological manifestations are mentioned in Table 43.1. Other rare subtypes of porphyrias that can present with neurological features are plumboporphyrias.
© Springer Nature Singapore Pte Ltd. 2018 S.V. Khadilkar et al., Neuromuscular Disorders, https://doi.org/10.1007/978-981-10-5361-0_43
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43 Porphyrias
Table 43.1 Porphyrias that present with neurological manifestations Subtypes of porphyria Acute intermittent porphyria (AIP) Hereditary coproporphyria (HCP) Variegate porphyria (VP) ALA dehydratase porphyria
Mode of inheritance Autosomal dominant
Enzyme deficiency PBG deaminase
Autosomal dominant
Coproporphyrinogen oxidase
Autosomal dominant
Protoporphyrinogen oxidase
Autosomal recessive
ALA dehydratase
Reaction catalysed PBG to hydroxymethylbilane
Coproporphyrinogen III to protoporphyrinogen IX Protoporphyrinogen IX to protoporphyrin IX ALA to PBG
Accumulated products PBG and ALA
PBG, ALA and coproporphyrins PBG, ALA, coproporphyrins and protoporphyrins ALA
43.2 Epidemiology AIP is the most prevalent form of acute porphyrias and is estimated to occur in 1 in 75,000 people in Europe. It is more common in Sweden, where it is seen in 1 in 1000 people. VP is twice as uncommon as AIP and is particularly common in South Africa. It is estimated to occur at 3/1000 in South African population, and a founder effect has been documented (Schutte et al. 2015; Puy et al. 2010). In the United States, prevalence of disease is 1 in 10–20 thousand populations. From India, case series and case reports of AIP have been reported (Mohanlal et al. 2016; Balwani et al. 2016; Divecha et al. 2016; Patell et al. 2016; Sharma et al. 2012; Kumar et al. 2010). Porphyrias are known to have a higher prevalence amongst some communities in Rajasthan (Bhargava and Gupta 1970; Sachdev et al. 2005; Mundhara et al. 1991). Porphyrias are more common in women than in men. Acute attacks are rare before puberty and after menopause with peak o
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