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Bone Abstracts (2017) 6 P037 | DOI: 10.1530/boneabs.6.P037

ICCBH2017 Poster Presentations (1) (209 abstracts)

Early fragility fractures in Zellweger syndrome spectrum – peroxisome dysfunction affecting osteogenesis?

Rachel Nicholls 1 , Germaine Pierre 2 , Effie Chronopoulou 2 , Sarah F Smithson 3 , Amaka C Offiah 4 , John S Barton 1 & Christine P Burren 1

1Department of Paediatric Endocrinology and Diabetes, Bristol Royal Hospital for Children, University Hospitals Bristol NHS Foundation Trust, Bristol, UK; 2Department of Paediatric Metabolic Medicine, Bristol Royal Hospital for Children, University Hospitals Bristol NHS Foundation Trust, Bristol, UK; 3Department of Clinical Genetics, St Michaels Hospital, University Hospitals Bristol NHS Foundation Trust, Bristol, UK; 4Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.

Background: Peroxisomal Biogenesis Disorders (PBD) is a group of rare metabolic diseases in which peroxisomal function is disrupted. PBD encompasses Zellweger Syndrome Spectrum (ZSS) disorders, which range in severity from classical ZS with severe neurological impairment and markedly reduced life expectancy to Refsum Disease presenting later in childhood. Recent fragility fractures in our ZSS patients in very early childhood prompted case series review.

Presenting problem: Amongst eight current ZSS patients (5M:3F, median age 2.3 years (range 0.7–19.4 years)), there were five fractures (at ages 0.5, 1.7, 4.5, 5 and 14.5 years): four femoral fractures (one patient had two femoral fractures) and one tibial and fibular following negligible force including normal handling. Patients presenting with fractures tended to have more severe neurological impairment.

Clinical management: All fractures were radiologically confirmed, minimally displaced and conservatively managed. Additional radiographic findings were osteopaenia (n=5), epiphyseal flattening (n=2), broad metaphyses (n=1), patellar stippling (n=1) and vertebral clefts (n=1). Those with fractures and older than 3 years had DEXA scans showing lumbar spine Bone Mineral Density (BMD) z scores −3.1 and −1.2. Intravenous bisphosphonates were commenced in the former (aged 14.5 years) and are under consideration for the latter (5 years). While the 14.5 year old had additional risk factors for reduced BMD (prolonged immobility, hypogonadism, anticonvulsants), three patients had femoral fractures at ages younger than expected purely from immobility.

Discussion: This case series demonstrates a high prevalence of fragility fractures in ZSS. A separate subgroup of PBD, rhizomelic chondrodysplasia punctata (RCDP), shares epiphyseal stippling as a common feature with ZSS. However fragility fractures are not a feature in RCDP. Reduced BMD in Peroxisomal Biogenesis Disorders can be multifactorial: hypotonia, immobility and impaired gonadal function. Peroxisomal dysfunction affecting bone formation is an additional possibility. Low BMD has been reported in ZSS, but fragility fracture before 5 years (our three ZSS patients) seems early to attribute to ‘simple osteopaenia’, supporting bone abnormality intrinsic to the PBD as the aetiology. This highlights the need for careful assessment of children with ZSS who sustain early fractures to determine the contributing factors and to inform judicious use of bisphosphonates.

Disclosure: The authors declared no competing interests.

Volume 6

8th International Conference on Children's Bone Health


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