How to Detect Isolated PEX10-Related Cerebellar Ataxia?

Esmeralda Nava; Britta Hartmann; Larissa Boxheimer; Andrea Capone Mori; Jean-Marc Nuoffer; Yelena Sargsyan; Sven Thoms; Hendrik Rosewich; Eugen Boltshauser

doi:10.1055/s-0041-1741383

Neuropediatrics, Inhaltsverzeichnis

Neuropediatrics 2022; 53(03): 159-166
DOI: 10.1055/s-0041-1741383

Original Article

How to Detect Isolated PEX10-Related Cerebellar Ataxia?

Esmeralda Nava

¹Department of Pediatric Neurology, Cantonal Hospital Aarau, Aarau, Switzerland

,

Britta Hartmann

²Department of Medical Genetics, Cantonal Hospital Aarau, Institute of Laboratory Medicine, Aarau, Switzerland

,

Larissa Boxheimer

³Department of Neuroradiology, Cantonal Hospital Aarau, Aarau, Switzerland

,

Andrea Capone Mori

¹Department of Pediatric Neurology, Cantonal Hospital Aarau, Aarau, Switzerland

,

Jean-Marc Nuoffer

⁴University Institute of Clinical Chemistry, Bern University Hospital, Bern, Switzerland

⁵University Children's Hospital Pediatric Endocrinology, Diabetology and Metabolism, Bern, Switzerland

,

Yelena Sargsyan

⁶Department of Pediatrics and Adolescent Medicine, University Medical Center Göttingen, Göttingen, Germany

,

Sven Thoms

⁶Department of Pediatrics and Adolescent Medicine, University Medical Center Göttingen, Göttingen, Germany

⁷Department of Biochemistry and Molecular Medicine, Medical School, Bielefeld University, Bielefeld, Germany

,

Hendrik Rosewich ^*

⁶Department of Pediatrics and Adolescent Medicine, University Medical Center Göttingen, Göttingen, Germany

,

Eugen Boltshauser ^*

⁸Department of Pediatric Neurology (emeritus), University Children's Hospital Zürich, Zürich, Switzerland

› Institutsangaben

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.

Keywords

ataxia - cerebellar atrophy - phytanic acid - PEX10 - peroxisomal disorders - screening tests

Volltext

Referenzen

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