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Zellweger syndrome and secondary mitochondrial myopathy

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Abstract

Defects in peroxisomes such as those associated with Zellweger syndrome (ZS) can influence diverse intracellular metabolic pathways, including mitochondrial functioning. We report on an 8-month-old female infant and a 6-month-old female infant with typical clinical, radiological and laboratory features of Zellweger syndrome; light microscopic and ultrastructural evidence of mitochondrial pathology in their muscle biopsies; and homozygous pathogenic mutations of the PEX16 gene (c.460 + 5G > A) and the PEX 12 gene (c.888_889 del p.Leu297Thrfs*12), respectively. Additionally, mitochondrial respiratory chain enzymology analysis in the first girl showed a mildly low activity in complexes II–III and IV. We also review five children previously reported in the literature with a presumptive diagnosis of ZS and additional mitochondrial findings in their muscle biopsies. In conclusion, this is the first study of patients with a molecularly confirmed peroxisomal disorder with features of a concomitant mitochondrial myopathy and underscores the role of secondary mitochondrial dysfunction in Zellweger syndrome, potentially contributing to the clinical phenotype.

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Abbreviations

CGH:

Comparative genomic hybridization

CSF:

Cerebrospinal fluid

MDS:

Mitochondrial depletion syndrome

MRI:

Magnetic resonance imaging

NG:

Nasogastric

PBD:

Peroxisomal biogenesis disorders

PEX:

Peroxines

PMP:

Peroxisomal membrane proteins

RCE:

Respiratory chain enzymes

SMA:

Spinal muscular atrophy

SMN:

Survival motor neuron

VLCFA:

Very long chain fatty acids

VSD:

Ventricular septal defect

ZS:

Zellweger syndrome

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Acknowledgments

We gratefully acknowledge Mrs Cathy Timson (Dubowitz Neuromuscular Centre) and Dr Glenn Anderson (Histopathology Department, Great Ormond Street Hospital) for their valuable contribution to electron microscopy. We wish to thank the two families who allowed us to report these two infants and provided us with informed consent for their inclusion in our study.

Conflicts of interest

We have not received any funds for this work. We received approval from our institutions for this study. We have no conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Paediatric Neurology, Chelsea and Westminster NHS Foundation Trust, London, UK

    Vincenzo Salpietro, Christos Fokoloros & Maria Kinali

  2. Department of Pediatrics, University of Messina, Messina, Italy

    Vincenzo Salpietro

  3. National Hospital for Neurology and Neurosurgery, London, UK

    Rahul Phadke

  4. St George’s Hospital, NHS Foundation Trust, London, UK

    Anand Saggar

  5. The Portland Hospital for Women and Children, London, UK

    Anand Saggar, Robert Yates, Kshitij Mankad, David McCormick & Maria Kinali

  6. Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK

    Iain P. Hargreaves

  7. Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK

    Robert Yates & Kshitij Mankad

  8. Tawam Hospital, United Arab Emirates National University, Al Ain, United Arab Emirates

    Jozef Hertecant

  9. Department of Educational Sciences, University of Catania, Catania, Italy

    Martino Ruggieri

  10. King’s College Hospital, NHS Foundation Trust, London, UK

    David McCormick

Authors
  1. Vincenzo Salpietro
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  2. Rahul Phadke
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  3. Anand Saggar
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  4. Iain P. Hargreaves
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  5. Robert Yates
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  6. Christos Fokoloros
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  7. Kshitij Mankad
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  8. Jozef Hertecant
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  9. Martino Ruggieri
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  10. David McCormick
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  11. Maria Kinali
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Corresponding author

Correspondence to Maria Kinali.

Additional information

Communicated by Beat Steinmann

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Salpietro, V., Phadke, R., Saggar, A. et al. Zellweger syndrome and secondary mitochondrial myopathy. Eur J Pediatr 174, 557–563 (2015). https://doi.org/10.1007/s00431-014-2431-2

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  • DOI: https://doi.org/10.1007/s00431-014-2431-2

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