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 1/200000. 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 pro-gressive 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.

Recent literature has highlighted the importance of transition from paediatric to adult care for children with chronic conditions. Non-cystic fibrosis bronchiectasis is an important cause of respiratory morbidity in low-income countries and in indigenous children from affluent countries; however, there is little information about adult outcomes of childhood bronchiectasis. We reviewed the clinical course of 31 Alaska Native adults 20-40 years of age from Alaska's Yukon Kuskokwim Delta with childhood bronchiectasis. In patients with chronic suppurative lung disease, a diagnosis of bronchiectasis was made at a median age of 4.5 years by computerised tomography (68%), bronchogram (26%), and radiographs (6%). The patients had a median of 75 lifetime respiratory ambulatory visits and 4.5 hospitalisations. As children, 6 (19%) experienced developmental delay; as adults 9 (29%) experienced mental illness or handicap. Four (13%) patients were deceased, four (13%) had severe pulmonary impairment in adulthood, 17 (54%) had persistent or intermittent respiratory symptoms, and seven (23%) were asymptomatic. In adulthood, only five were seen by adult pulmonologists and most had no documentation of a bronchiectasis diagnosis. Lack of provider continuity, remote location and co-morbidities can contribute to increased adult morbidity. Improving the transition to adult care starting in adolescence and educating adult providers may improve care of adults with childhood bronchiectasis.

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