P2.106: The Flip Side of Sanfilippo Syndrome: A Case of Atypical Timing and Presentation

Introduction: Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a rare, devastating lysosomal storage disorder characterized by neurocognitive deterioration and childhood dementia. Typically, Sanfilippo syndrome manifests as a global developmental delay after a period of normal development and is diagnosed around age 1-4. Physical manifestations are commonly musculoskeletal but include developmental and behavioral disorders, gastrointestinal problems, cardiovascular complications, and respiratory diseases. While primary lung involvement is a common feature of lysosomal storage disorders like Niemann-Pick disease, Fabry disease, and Gaucher disease, it is an extremely rare initial manifestation of MPS IIIA. A literature search fails to demonstrate reports of newborn respiratory failure as the initial and primary presentation of MPS IIIA.

Case Description: The authors present a case of hypoxemic, hypercapnic respiratory failure secondary to pulmonary hypoplasia and interstitial fibrosis as the initial presentation of MPS IIIA in a newborn male born at 38 weeks gestation. Within an hour of delivery, the patient was noted to be in respiratory distress, requiring oxygen support with high flow nasal cannula, escalation to continuous positive airway pressure, then intubation for mechanical ventilation, and admission to a level IV NICU. His treatment included oxygen support, surfactant, chest physiotherapy with budesonide and hypertonic albuterol, diuresis, high-dose steroids, and antibiotics with minimal improvement. He continued to require supplemental oxygen and CPAP support at 1 month of life. The patient underwent a chest CT which demonstrated a diffuse hazy ground glass opacities with superimposed interlobular septal thickening of the bilateral lungs. Additionally, there was a mosaic pattern of hyperinflation and atelectasis. A lung biopsy demonstrated alveolar hypoplasia, interstitial inflammation, and mild interstitial fibrosis. It was not until two months of life that whole exome sequencing results revealed a homozygous pathogenic variant in the SGSH gene, consistent with Sanfilippo syndrome.

Discussion: While respiratory symptoms secondary to hypotonia and neuromuscular weakness present as a later finding in Sanfilippo syndrome, respiratory distress at birth is not a typical feature. Alveolar hypoplasia leads to decreased surface area for gas exchange while interstitial fibrosis and inflammation may result in diffusion limitations and decreased lung compliance. The culmination of immature lung development and interstitial lung disease result in persistent hypoxemia and need for prolonged respiratory support. While pulmonary prognosis is difficult to determine given the absence of comparable cases, this patient has been able to wean off respiratory support over time which is likely reflective of continued growth of new, healthy lung tissue.

Conclusion: The authors highlight a rare case of Sanfilippo Syndrome in a neonate with respiratory failure. This case emphasizes the importance of considering genetic disorders in neonates with unexplained respiratory failure and chronic lung inflammation. It also underscores the role of early genetic testing in identifying rare diseases that may present atypically.