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MRI characterisation of adult onset alpha-methylacyl-coA racemase deficiency diagnosed by exome sequencing

Kristoffer Haugarvoll12, Stefan Johansson34, Charalampos Tzoulis12, Bjørn Ivar Haukanes3, Cecilie Bredrup35, Gesche Neckelmann6, Helge Boman23, Per Morten Knappskog23 and Laurence A Bindoff12*

Author Affiliations

1 Department of Neurology, Haukeland University Hospital, Bergen, Norway

2 Department of Clinical Medicine, University of Bergen, Bergen, Norway

3 Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway

4 Department of Biomedicine, University of Bergen, Bergen, Norway

5 Department of Ophthalmology, Haukeland University Hospital, Bergen, Norway

6 Department of Radiology, Haukeland University Hospital, Bergen, Norway

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Orphanet Journal of Rare Diseases 2013, 8:1  doi:10.1186/1750-1172-8-1

Published: 3 January 2013



Correct diagnosis is pivotal to understand and treat neurological disease. Herein, we report the diagnostic work-up utilizing exome sequencing and the characterization of clinical features and brain MRI in two siblings with a complex, adult-onset phenotype; including peripheral neuropathy, epilepsy, relapsing encephalopathy, bilateral thalamic lesions, type 2 diabetes mellitus, cataract, pigmentary retinopathy and tremor.


We applied clinical and genealogical investigations, homozygosity mapping and exome sequencing to establish the diagnosis and MRI to characterize the cerebral lesions.


A recessive genetic defect was suspected in two siblings of healthy, but consanguineous parents. Homozygosity mapping revealed three shared homozygous regions and exome sequencing, revealed a novel homozygous c.367 G>A [p.Asp123Asn] mutation in the α-methylacyl-coA racemase (AMACR) gene in both patients. The genetic diagnosis of α-methylacyl-coA racemase deficiency was confirmed by demonstrating markedly increased pristanic acid levels in blood (169 μmol/L, normal <1.5 μmol/L). MRI studies showed characteristic degeneration of cerebellar afferents and efferents, including the dentatothalamic tract and thalamic lesions in both patients.


Metabolic diseases presenting late are diagnostically challenging. We show that appropriately applied, homozygosity mapping and exome sequencing can be decisive for establishing diagnoses such as late onset α-methylacyl-coA racemase deficiency, an autosomal recessive peroxisomal disorder with accumulation of pristanic acid. Our study also highlights radiological features that may assist in diagnosis. Early diagnosis is important as patients with this disorder may benefit from restricted dietary phytanic and pristanic acid intake.

AMACR gene; Seizures; Next generation sequencing; Ataxia; Peroxisomal disorders; Metabolic disorders; Tremor; Peripheral neuropathy; Pigmentary retinopathy