How to Detect Isolated PEX10-Related Cerebellar Ataxia?

Nava, Esmeralda; Hartmann, Britta; Boxheimer, Larissa; Capone Mori, Andrea; Nuoffer, Jean-Marc; Sargsyan, Yelena; Thoms, Sven; Rosewich, Hendrik; Boltshauser, Eugen (2022). How to Detect Isolated PEX10-Related Cerebellar Ataxia? Neuropediatrics, 53(3), pp. 159-166. Thieme 10.1055/s-0041-1741383

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Endocrinology/Metabolic Disorders

UniBE Contributor:

Nuoffer, Jean-Marc

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1439-1899

Publisher:

Thieme

Language:

English

Submitter:

Anette van Dorland

Date Deposited:

07 Feb 2022 07:50

Last Modified:

05 Dec 2022 16:04

Publisher DOI:

10.1055/s-0041-1741383

PubMed ID:

35038753

BORIS DOI:

10.48350/164544

URI:

https://boris.unibe.ch/id/eprint/164544

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