Neonatal Onset Interstitial Lung Disease as a Primary Presenting Manifestation of Mucopolysaccharidosis Type I

Abstract

We describe two cases of neonatal onset interstitial lung disease eventually diagnosed as mucopolysaccharidosis type I (MPS I). In both cases, evaluation led to lung biopsy, pathology review, and identification of glycogen deposition. Pulmonary interstitial glycogenosis (PIG) was considered as a clinical diagnosis in case one; however, further review of electron microscopy (EM) was more consistent with MPS I rather than PIG. Both cases were confirmed to have MPS I by enzyme and molecular analysis. Neonatal interstitial lung disease is an atypical presentation for MPS I which is likely under-recognized. Diagnosis through clinical guidelines and a multidisciplinary approach had a major impact on patient management. The diagnosis of MPS I prompted timely initiation of enzyme replacement therapy (ERT) and the patients ultimately underwent hematopoietic stem cell transplantation (HSCT) to improve symptomatic outcomes. In addition to treatment, immediate precautionary recommendations were made to avoid potentially catastrophic outcomes associated with cervical instability. These cases add to the clinical spectrum of MPS I in the newborn period. They further illustrate the difficulties in early recognition of the disease, and importance of a definitive diagnosis of MPS I in infants with interstitial lung disease.

Douglas Bush and Leighann Sremba are co-first authors.

Appendices

Synopsis

Neonatal interstitial lung disease is an under-recognized disease manifestation of mucopolysaccharidosis type I (MPS I). We describe two cases of neonatal onset interstitial lung disease initially identified to have glycogen deposition on pathology, although further review of electron microscopy and the clinical phenotype led to a diagnosis of MPS I in both patients.

Details of the Contributions of Individual Authors

Douglas Bush participated in writing the manuscript and was closely involved in the review and revision. Leighann Sremba participated in writing the manuscript with involvement in the continued review and revision. Kate Lomax participated in drafting the clinical description for Case 2, and reviewing and revising the manuscript. Jill Lipsett participated in the clinical and pathology description, and providing pathology specimens for Case 2. David Ketteridge participated in writing and revising the clinical description for Case 2. Drago Bratkovic participated in the clinical and pathology description for Case 2. Yazmin Enchautegui-Colon participated in the metabolic investigations and writing the initial clinical description in Case 1. James Weisfeld-Adams provided clinical care for Case 1 and participated in the review and revision of the manuscript providing genetic and metabolic expertise. Csaba Galambos participated in the pathologic description for both cases, reviewed and revised the manuscript and provided expertise in pathologic diagnosis of PIG. Seth Lummus participated in the pathologic descriptions for both cases, reviewed and revised the manuscript. Eric Wartchow was involved in the initial pathologic description, reviewed and revised the manuscript, provided electron microscopy support, and created figures with legends. Deborah Liptzin wrote the discussion on cHILD syndrome, provided clinical descriptions for PIG, and revised the manuscript. Peter Baker II oversaw the writing and organization of the manuscript, was responsible for the clinical diagnosis of Case 1, participated in multidisciplinary discussions about the manuscript, and reviewed and edited the manuscript.

Peter Baker is the corresponding author and takes full responsibility for the manuscript’s content.

Compliance With Ethics and Guidelines

Conflict of Interest

Douglas Bush, Leighann Sremba, Kate Lomax, Jill Lipsett, David Ketteridge, Drago Bratkovic, Yazmin Enchautegui-Colon, James Weisfeld-Adams, Csaba Galambos, Seth Lummus, Eric Wartchow, Jason Weinman, Deborah R. Liptzin, and Peter Baker II declare that they have no conflict of interest.

The authors have not received any honorarium or payment to produce the manuscript. There are no study sponsors involved.

Informed consent was obtained from all patients for which identifying information is included in this chapter.

Prior Abstract Publication/Presentation

Poster presentation at the Society for Inherited Metabolic Disorders annual conference April 3rd, 2016 titled “Evaluation of chILD syndrome leads to early diagnosis of MPS I.”