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Phenotyping heterozygous carriers of juvenile neuronal ceroid lipofuscinosis with CLN3 mutations

  • Retinal Disorders
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Abstract

Purpose

The objective of this study was to establish an ophthalmologic phenotype of heterozygous carriers of juvenile neuronal ceroid lipofuscinosis (CLN3 disease, Batten disease).

Methods

The eyes and vision of nine heterozygous carriers of juvenile neuronal ceroid lipofuscinosis with classical CLN3 mutations were examined using the following methods: clinical examination, visual acuity, ophthalmoscopy, optical coherence tomography (macular thickness and peripapillary retinal nerve fibre layer measurement [RNFL]), fundus autofluorescence measurement, infrared imaging, and full-field and multifocal electroretinogram. Optical coherence tomography and electrophysiological data were statistically compared with age- and sex-matched control groups.

Results

The basic clinical examination as well as the fundus autofluorescence and infrared images of the macular region were unremarkable. Neither the electrophysiological examinations nor optical coherence tomography yielded fundamental abnormalities. There were only two significant—albeit most likely clinically irrelevant—differences that occurred in comparison to the control group: a decrease in RNFL of the nasal quadrant in the OCT and a prolongation of the N1 implicit time of the second-ring eccentricity in the multifocal electroretinogram.

Conclusions

The eyes and vision of heterozygous carriers of CLN3 disease showed normal features when compared to a control group, which controverts a previously suggested retinal dysfunction in these subjects.

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Acknowledgments

Funding/ Support

This study was funded by donations from the Nächstenliebe (www.ncl-naechstenliebe.de) and Freunde der Kinderklinik UK Eppendorf e.V foundations. Funds were used solely as expense allowance for the participating subjects. All subjects had to travel to Berlin from other parts of Germany. Some subjects stayed overnight in a hotel near the university campus.

Contributions of authors

Design and conduct of the study: RB. AK. AS. WH. KR.

Collection of data: RB. KR.

Management, analysis, and interpretation of data: RB. AK. AS. KR.

Preparation, review, and approval of the manuscript: RB. AK. AS. KR.

Statement regarding conformity of author information

This study was prospectively approved by the ethics committee of the Charité (Ethikkommission der Charité – Universitätsmedizin, Berlin), and all subjects gave informed consent to participate in the trial.

The authors would like to thank Carola Lehrhaft, Anja Brune, and Dirk Scharf for their support with the electrophysiological recordings and retinal imaging.

Conflict of interest

None

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Authors and Affiliations

  1. Department of Ophthalmology, Charité – Universitätsmedizin Berlin, Berlin, Germany

    Richard Bergholz

  2. Children’s Hospital, University Medical Center Eppendorf, Hamburg, Germany

    Alfried Kohlschütter, Angela Schulz & Waltraud Hubert

  3. Department of Ophthalmology, Sankt Gertrauden-Krankenhaus, Berlin, Germany

    Klaus Rüther

  4. Charité Augenklinik Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany

    Richard Bergholz

Authors
  1. Richard Bergholz
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  2. Alfried Kohlschütter
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  3. Angela Schulz
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  4. Waltraud Hubert
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  5. Klaus Rüther
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Corresponding author

Correspondence to Richard Bergholz.

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Bergholz, R., Kohlschütter, A., Schulz, A. et al. Phenotyping heterozygous carriers of juvenile neuronal ceroid lipofuscinosis with CLN3 mutations. Graefes Arch Clin Exp Ophthalmol 253, 1245–1250 (2015). https://doi.org/10.1007/s00417-014-2814-0

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  • DOI: https://doi.org/10.1007/s00417-014-2814-0

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