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Licensed Unlicensed Requires Authentication Published by De Gruyter June 18, 2019

Hereditary hyperferritinaemia-cataract syndrome (HHCS) – an underestimated condition: ferritin light chain variant spectrum in German families

Martin Volkmann EMAIL logo , Rudolf Richter , Thomas Herrmann , Sabine Hentze , Michaela Hör , Hendrik Hasche , Barbara Selle , Wolfgang Stremmel and Sven G. Gehrke

Abstract

Background

In hereditary hyperferritinaemia-cataract syndrome (HHCS), single nucleic acid alterations in the ferritin light chain (L-ferritin) iron response element (IRE) constitutively derepress ferritin synthesis, resulting in hyperferritinaemia, L-ferritin deposits in the lens of the eye and early bilateral cataract onset.

Methods

In this study, six German families with putative HHCS were analysed. Clinical diagnosis of HHCS was based on medical history, evaluation of ferritin serum levels, transferrin saturation and clinical ophthalmological examination. Diagnosis was confirmed by polymerase chain reaction (PCR)-based DNA sequencing of the L-ferritin IRE.

Results

Genetic analysis of the L-ferritin IRE revealed relevant single nucleic acid alterations in each of the affected families. Variants c.-168G > A, c.-168G > U and c.-167C > U were located in the C-bulge region; and variants c.-161C > U and c.-157G > A were located in the hexanucleotide loop of the L-ferritin IRE.

Conclusions

Family history of hyperferritinaemia and juvenile cataracts are strong indicators of HHCS. Genetic analysis of the L-ferritin IRE is a straightforward procedure to confirm the diagnosis. Accurate diagnosis of hyperferritinaemia can avoid unnecessary treatment by venesection, and focus attention on early cataract detection in offspring at risk.


Corresponding author: PD Dr. Martin Volkmann, MVZ Labor PD Dr. Volkmann & Kollegen GbR, Kriegsstr. 99, D-76133 Karlsruhe, Germany

Award Identifier / Grant number: STR 216/10-1

Funding statement: Supported by grant no: STR 216/10-1 (funder Id: http://dx.doi.org/10.13039/501100001659) of the Deutsche Forschungsgemeinschaft and the Dietmar Hopp Foundation.

Acknowledgments

We wish to thank Karin Bents for expert technical assistance.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Employment or leadership: None declared.

  3. Honorarium: None declared.

  4. Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2018-12-20
Accepted: 2019-05-19
Published Online: 2019-06-18
Published in Print: 2019-11-26

©2019 Walter de Gruyter GmbH, Berlin/Boston

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