Neuropediatrics
DOI: 10.1055/s-0041-1741383
Original Article

How to Detect Isolated PEX10-Related Cerebellar Ataxia?

1   Department of Pediatric Neurology, Cantonal Hospital Aarau, Aarau, Switzerland
,
2   Department of Medical Genetics, Cantonal Hospital Aarau, Institute of Laboratory Medicine, Aarau, Switzerland
,
Larissa Boxheimer
3   Department of Neuroradiology, Cantonal Hospital Aarau, Aarau, Switzerland
,
Andrea Capone Mori
1   Department of Pediatric Neurology, Cantonal Hospital Aarau, Aarau, Switzerland
,
4   University Institute of Clinical Chemistry, Bern University Hospital, Bern, Switzerland
5   University Children's Hospital Pediatric Endocrinology, Diabetology and Metabolism, Bern, Switzerland
,
6   Department of Pediatrics and Adolescent Medicine, University Medical Center Göttingen, Göttingen, Germany
,
6   Department of Pediatrics and Adolescent Medicine, University Medical Center Göttingen, Göttingen, Germany
7   Department of Biochemistry and Molecular Medicine, Medical School, Bielefeld University, Bielefeld, Germany
,
6   Department of Pediatrics and Adolescent Medicine, University Medical Center Göttingen, Göttingen, Germany
,
8   Department of Pediatric Neurology (emeritus), University Children's Hospital Zürich, Zürich, Switzerland
› Author Affiliations

Abstract

A 4-year-old boy presented with subacute onset of cerebellar ataxia. Neuroimaging revealed cerebellar atrophy. Metabolic screening tests aiming to detect potentially treatable ataxias showed an increased value (fourfold upper limit of normal) for phytanic acid and elevated very-long-chain fatty acid (VLCFA) ratios (C24:0/C22:0 and C26:0/C22:0), while absolute concentrations of VLCFA were normal. Genetic analysis identified biallelic variants in PEX10. Immunohistochemistry confirmed pathogenicity in the patients' cultured fibroblasts demonstrating peroxisomal mosaicism with a general catalase import deficiency as well as conspicuous peroxisome morphology as an expression of impaired peroxisomal function. We describe for the first time an elongated peroxisome morphology in a patient with PEX10-related cerebellar ataxia.

A literature search yielded 14 similar patients from nine families with PEX10-related cerebellar ataxia, most of them presenting their first symptoms between 3 and 8 years of age. In 11/14 patients, the first and main symptom was cerebellar ataxia; in three patients, it was sensorineural hearing impairment. Finally, all 14 patients developed ataxia. Polyneuropathy (9/14) and cognitive impairment (9/14) were common associated findings. In 12/13 patients brain MRI showed cerebellar atrophy. Phytanic acid was elevated in 8/12 patients, while absolute concentrations of VLCFA levels were in normal limits in several patients. VLCFA ratios (C24:0/C22:0 and/or C26:0/C22:0), though, were elevated in 11/11 cases. We suggest including measurement of phytanic acid and VLCFA ratios in metabolic screening tests in unexplained autosomal recessive ataxias with cerebellar atrophy, especially when there is an early onset and symptoms are mild.

Consent for Publication

Informed consent to publish the data in this report was obtained from the patient's parents.


Disclosures

The authors do not have any conflicts of interest.




Publication History

Received: 16 July 2021

Accepted: 23 November 2021

Publication Date:
17 January 2022 (online)

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