Medical and financial burden of acute intermittent porphyria

Introduction: A small proportion of patients with acute intermittent porphyria (AIP) suffer from recurrent porphyric attacks, with a severely diminished quality of life. In this retrospective case-control study, the burden of disease is quantified and compared among three AIP patient subgroups: cases with recurrent attacks, cases with one or occasional attacks and asymptomatic carriers. Methods: Data from patient records and questionnaires were collected in patients between 1960 and 2016 at the Erasmus Medical Center, Rotterdam, the Netherlands. We collected symptoms related to porphyria, porphyria related complications, attack frequency, hospitalisation frequency, hospitalisation days related to acute porphyric attacks, frequency of heme infusions and medical healthcare costs based on hospitalisations and heme therapy. Results: In total 11 recurrent AIP cases, 24 symptomatic AIP cases and 53 AIP carriers as controls were included. All recurrent patients reported porphyria related symptoms, such as pain, neurological and/or psychiatric disorders, and nearly all developed complications, such as hypertension and chronic kidney disease. In the recurrent cases group, the median lifelong number of hospitalisation days related to porphyric attacks was 82 days per patient (range 10–374), and they spent a median of 346 days (range 34–945) at a day-care facility for prophylactic heme therapy; total follow-up time was 243 person-years (PYRS). In the symptomatic non-recurrent group the median lifelong number of hospitalisation days related to porphyric attacks was 7 days per patient (range 1–78), total follow-up time was 528 PYRS. The calculated total medical healthcare cost for recurrent cases group was €5.8 million versus €0.3 million for the symptomatic cases group

Acute intermittent porphyria-related leukoencephalopathy

Objective: To identify the genetic etiology of a distinct leukoencephalopathy with autosomal recessive inheritance in a single family. Methods: We analyzed available MRIs and retrospectively reviewed clinical information and laboratory investigations. We performed whole-exome sequencing to find the causal gene variants. Results: We identified 3 family members with a similar MRI pattern characterized by symmetrical signal abnormalities in the periventricular and deep cerebral white matter, thalami, and central part of the pons. Cerebellar atrophy was noted in advanced disease stages. Clinical features were childhood-onset slowly progressive spastic paraparesis, cerebellar ataxia, peripheral neuropathy, and in 2 patients, optic atrophy as well as vertical gaze and convergence palsies and nystagmus. Whole-exome sequencing revealed compound heterozygous missense variants in the HMBS gene, both associated with the autosomal dominant disorder acute intermittent porphyria. Sanger sequencing of 6 healthy siblings confirmed the bi-allelic location of the variants and segregation with the disease. Patients had a slight and moderate increase in urinary and plasma porphobilinogen and 5′-aminolevulinic acid, respectively, and a 50% to 66% decrease in hydroxymethylbilane synthase enzyme activity compared to normal. Conclusions: Bi-allelic HMBS variants have been reported before as cause of severe encephalopathy with early childhood fatality in acute intermittent porphyria. Our cases demonstrate childhood onset, but milder and slower disease progression in middle-aged patients. With this, a novel phenotype can be added to the disease spectrum associated with bi-allelic HMBS variants: a leukoencephalopathy with early onset, slowly progressive neurologic symptomatology, and long life expectancy

Clinical Remission of Delta-Aminolevulinic Acid Dehydratase Deficiency through Suppression of Erythroid Heme Synthesis

We present a case of delta-aminolevulinic acid dehydratase-porphyria (ADP) who was successfully treated by suppressing bone-marrow production of toxic heme precursors. Together with supporting evidence from earlier cases, it is likely ADP has both hepatic and erythroid origins. This article is protected by copyright. All rights reserved