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Hereditary Hyperferritinemia -Cataract Syndrome: Prevalence, lens morphology and spectrum of mutations and clinical presentations

Citation

Craig, JE and Clark, JB and McLeod, JL and Kirkland, MA and Grant, G and Elder, JE and Toohey, MG and Kowal, L and Chen, C and Wirth, MG and Mackey, DA, Hereditary Hyperferritinemia -Cataract Syndrome: Prevalence, lens morphology and spectrum of mutations and clinical presentations, Archives of Opthalmology, 121, (12) pp. 1753-1761. ISSN 0003-9950 (2003) [Refereed Article]

DOI: doi:10.1001/archopht.121.12.1753

Abstract

Objectives: To provide a comprehensive description of the clinical presentations, cataract morphology, and molecular basis of hereditary hyperferritinemia-cataract syndrome (HHCS) in 4 Australian pedigrees and to estimate its prevalence. Methods: All known cases of HHCS in southeastern Australia were ascertained. Family members provided a medical history and underwent physical examination, lens photography, and venipuncture for measurement of serum ferritin levels and DNA extraction. Sequence analysis of the iron-responsive element of the ferritin light chain on chromosome 19q13.3-qter was performed. Results: We investigated 26 affected individuals from 5 Australian pedigrees. Two pedigrees with HHCS ascertained independently were subsequently found to form 1 large kindred carrying the mutation A40G. The minimum estimated prevalence of HHCS is 1/200 000. One pedigree had the mutation G32C. Among 2 smaller pedigrees studied, one carried a novel mutation (C39A), and the other was identified through the 2-year-old propositus with cataract but no positive family history. The latter case was shown to be due to a de novo mutation (G32U). All cataracts were highly distinctive in morphology, consisting of slowly progressive flecks, vacuoles, and distinctive crystalline deposits scattered predominantly in the lens cortex but also in the nucleus. Eight of 18 affected individuals examined have required cataract extraction to date. No other identified clinical manifestations of HHCS were delineated. Conclusions: Cataract morphology in HHCS is highly distinctive. Longitudinal observation demonstrated slow progression of the cataracts. This study highlights that, although HHCS is an autosomal dominant condition, the diagnosis should be considered even in sporadic cataract of typical morphology. Furthermore, individuals with unexplained hyperferritinemia should be referred for ophthalmological assessment, as the cataract may be asymptomatic but lead to a correct diagnosis of HHCS. Clinical Relevance: Progressive cataracts of highly distinctive morphology are an important feature of HHCS. Evaluation for this type of cataract may be of diagnostic value in patients with unexplained hyperferritinemia. Hereditary hyperferritinemia-cataract syndrome can be a cause of cataracts in pediatric patients even in the absence of any positive family history.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Ophthalmology and Optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Hearing, Vision, Speech and Their Disorders
Author:Craig, JE (Mr Jamie Craig)
Author:Mackey, DA (Professor David Mackey)
ID Code:48951
Year Published:2003
Web of Science® Times Cited:42
Deposited By:Menzies Institute for Medical Research
Deposited On:2007-08-01
Last Modified:2011-09-21
Downloads:0

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