Home Medicine Hereditary hyperferritinaemia-cataract syndrome (HHCS) – an underestimated condition: ferritin light chain variant spectrum in German families
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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
Published/Copyright: June 18, 2019
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 57 Issue 12

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.

Keywords: cataract; ferritin; hyperferritinaemia; IRE side
Corresponding author: PD Dr. Martin Volkmann, MVZ Labor PD Dr. Volkmann & Kollegen GbR, Kriegsstr. 99, D-76133 Karlsruhe, Germany

Funding source: Deutsche Forschungsgemeinschaft

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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https://doi.org/10.1515/cclm-2018-1354
Keywords for this article
cataract; ferritin; hyperferritinaemia; IRE side

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. The re-emergence of dried blood spot sampling – are we ready?
  4. Review
  5. The role of platelets in bleeding in patients with thrombocytopenia and hematological disease
  6. Opinion Paper
  7. Exertional hematuria: definition, epidemiology, diagnostic and clinical considerations
  8. Guidelines and Recommendations from Scientific Societies
  9. A protocol for testing the stability of biochemical analytes. Technical document
  10. Genetics and Molecular Diagnostics
  11. Hereditary hyperferritinaemia-cataract syndrome (HHCS) – an underestimated condition: ferritin light chain variant spectrum in German families
  12. General Clinical Chemistry and Laboratory Medicine
  13. Performance of a web-based application measuring spot quality in dried blood spot sampling
  14. Clinical application of a dried blood spot assay for sirolimus and everolimus in transplant patients
  15. Plasma and dried blood spot lysosphingolipids for the diagnosis of different sphingolipidoses: a comparative study
  16. Liquid biopsy of cerebrospinal fluid identifies neuronal pentraxin receptor (NPTXR) as a biomarker of progression of Alzheimer’s disease
  17. Integrity of serum samples is changed by modified centrifugation conditions
  18. Heparin and citrate additive carryover during blood collection
  19. Copeptin – a biomarker of short-term mortality risk (7 days) in patients with end-stage liver disease
  20. Comparison of a new rapid method for the determination of adalimumab serum levels with two established ELISA kits
  21. Measurement of α-dicarbonyl compounds in human saliva by pre-column derivatization HPLC
  22. Establishment of the intelligent verification criteria for a routine urinalysis analyzer in a multi-center study
  23. Reference Values and Biological Variations
  24. A new indirect estimation of reference intervals: truncated minimum chi-square (TMC) approach
  25. EGFR and EGFR ligands in serum in healthy women; reference intervals and age dependency
  26. Early pregnancy reference intervals; 29 serum analytes from 4 to 12 weeks’ gestation in naturally conceived and uncomplicated pregnancies resulting in live births
  27. Paediatric reference intervals for 17 Roche cobas 8000 e602 immunoassays in the CALIPER cohort of healthy children and adolescents
  28. Hematology and Coagulation
  29. Study of the analytical performance at different concentrations of hematological parameters using Spanish EQAS data
  30. Multicenter performance evaluation of the Abbott Alinity hq hematology analyzer
  31. Cardiovascular Diseases
  32. Fast 0/1-h algorithm for detection of NSTEMI: are current high-sensitivity cardiac troponin assays fit for purpose? An EQA-based evaluation
  33. Infectious Diseases
  34. Diagnostic performance of cerebrospinal fluid free light chains in Lyme neuroborreliosis – a pilot study
  35. Letters to the Editor
  36. Quality management at the national biobanking level – establishing a culture of mutual trust and support: the BBMRI.at example
  37. Molecular diagnosis of MODY3 permitted to reveal a de novo 12q24.31 deletion and to explain a complex phenotype in a young diabetic patient
  38. Increased C-reactive protein values in the absence of inflammation: monoclonal immunoglobulin interference in immunonephelometry
  39. An approach based on simulated hemolysis for establishing the hemolysis index threshold for high-sensitivity cardiac troponin T assay
  40. Utility of the icteric index for the management of bilirubin test requesting
  41. Quality control of monocyte volume and distribution width parameters of the Beckman Coulter DxH series
  42. Mozhaisk haemoglobin variant effects on leukocyte differential channel using the Sysmex XN series
  43. Detection of a novel hemoglobin variant Hb Liaoning by matrix assisted laser desorption/ionization-time of flight mass spectrometry
  44. Appropriateness of repetitive therapeutic drug monitoring and laboratory turnaround time
  45. Congress Abstracts
  46. 51th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC – Laboratory Medicine)
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