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Pulmonary involvement in Niemann-Pick C type 1

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Abstract

Niemann-Pick disease type C (NPC) is a lysosomal storage disorder caused by mutations in either NPC-1 or NPC-2 genes, resulting in abnormal intracellular cholesterol trafficking. The estimated prevalence of NPC disease is 1: 120,000–150,000. Lung involvement has been described in only few patients with NPC, mostly NPC2. We describe a series of 12 patients, originating from six families all homozygotes to the p.R404Q (c.1211G > A) mutation of NPC1 gene; nine of them had significant pulmonary manifestations. All patients were followed in our medical center. Nine of the patients had pulmonary involvement, with recurrent pneumonia as the first manifestation in most, followed by recurrent wheezing episodes and subsequent development of interstitial lung disease with chronic need for oxygen support. Seven patients were reported of having interstitial disease by various imaging modalities.

Conclusion: Pulmonary involvement in NPC1 is more common than previously reported. It is characterized as primary obstructive and restrictive lung disease and not only as part of neurologic sequel of NPC. It can lead to respiratory insufficiency and death from respiratory failure.

What is Known:

• Lung involvement has been described in only few patients with NPC.

• Most reported NPC cases with pulmonary involvement were of NPC2.

What is New:

• Pulmonary involvement in NPC1 is more common than previously reported.

• Pulmonary involvement in NPC1 should be considered as part of the disease and be thoroughly assessed and managed.

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Abbreviations

EM:

Electron microscope

LAMP1:

Lysosomal associated membrane protein 1

NPC:

Niemann-Pick disease type C

PFTs:

Pulmonary function tests

VSGP:

Vertical supranuclear gaze palsy

BAL:

Bronchoalveolar lavage

CT:

Computerized tomography

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Author information

Authors and Affiliations

  1. Pediatric Metabolic Clinic, Pediatric Division, Soroka Medical Center, Ben-Gurion University, Beersheba, Israel

    Orna Staretz-Chacham & E. Hershkovitz

  2. Pediatric Pulmonology Clinic, Pediatric Division, Soroka Medical Center, Ben-Gurion University, Beersheba, Israel

    M. Aviram & A. Goldbart

  3. Department of Pediatrics, The Edmond and Lily Safra Children’s Hospital, Chaim Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel

    I. Morag

Authors
  1. Orna Staretz-Chacham
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  2. M. Aviram
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  3. I. Morag
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  4. A. Goldbart
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  5. E. Hershkovitz
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Contributions

Orna Staretz Chacham was responsible for planning, conducting, and reporting of the study.

Micha Aviram and Iris Morag contributed for the conducting and reporting of the work.

Aviv Goldbart contributed for reporting of the study.

Eli Hershkovitz contributed for the planning and reporting of the study.

Corresponding author

Correspondence to Orna Staretz-Chacham.

Ethics declarations

This article does not contain any studies with human or animal subjects performed by the any of the authors; therefore, no informed consent was required. The study was approved by the Helsinki Committee of the institution.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Communicated by Peter de Winter

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Staretz-Chacham, O., Aviram, M., Morag, I. et al. Pulmonary involvement in Niemann-Pick C type 1. Eur J Pediatr 177, 1609–1615 (2018). https://doi.org/10.1007/s00431-018-3219-6

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  • DOI: https://doi.org/10.1007/s00431-018-3219-6

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