P3.283: Delayed Diagnosis of GM1 Gangliosidosis: Lessons in Identifying Pediatric Red Flags for Lysosomal Storage Disorders

Introduction: GM1 gangliosidosis is a rare lysosomal storage disorder caused by β-galactosidase deficiency secondary to mutations in the GLB1 gene. Given its predilection for the nervous system, GM1 ganglioside accumulates to toxic levels resulting in progressive neurodegeneration, developmental regression, and eventual multisystem involvement. Early diagnosis, while not necessarily altering prognosis, remains essential for initiating appropriate supportive care, providing family guidance, and facilitating access to therapies. We present the case of a 14-month-old female diagnosed with GM1 gangliosidosis Type 1 following five months of unrecognized clinical red flags.

Case Description: Patient was born at 39+4 weeks via C-section. She failed the newborn hearing screen. She had bilateral myringotomy tubes at 3 months, with diagnosis of sensorineural hearing loss at 4 months prompting medevac to Bethesda, MD. Hyperpigmented macules first noticed by parents at 1 month, documented in EMR at 5 and 6 months. A 6-month visit, development was documented to be on track, but the subsequent follow-up noted developmental delays including poor head control, weak truncal balance, and not passing objects. Dermatology evaluation at 7 months revealed scattered lesions consistent with dermal melanocytosis, combined with the sensorineural hearing loss prompted genetics referral for suspected lysosomal storage disorder. Genetics assessment at 8 months noted significant developmental delays, nystagmus, hypotonia, and coarse facies. Ophthalmology confirmed cherry-red spots on retinal exam, supporting the leading diagnosis of a lysosomal storage disorder. Disease progression has included worsening neurologic function (truncal hypotonia, extremity spasticity, seizures), feeding difficulties requiring GT placement, developmental regression, and deteriorating hearing/vision.

Discussion: The patient initially displayed diffuse congenital dermal melanocytoses, coarse facies, hypotonia, and global developmental delay—an unmistakable constellation of signs suggestive of a lysosomal storage disorder. This case highlights the value of recognizing extensive dermal melanocytosis, distinct from typical congenital melanocytosis, as a clinical clue in conjunction with neurologic or developmental symptoms for identifying lysosomal storage disorders. Earlier recognition may have facilitated access to family support, genetic counseling, and early interventions to improve the family’s quality of life, despite the poor long-term prognosis. Unfortunately, patients with this condition are not eligible for enzyme replacement therapy, and there are no current curative or disease altering treatments. Management prioritizes symptomatic care, including feeding support, physical therapy, and palliative interventions.

Conclusion: When uncovering a constellation of abnormal findings, it is critical to consider rare and genetic causes that may have an opportunity to treat or halt the progression of disease. This case illustrates the need for this heightened awareness of rare conditions like GM1 gangliosidosis in pediatric practice and reinforces the value of prompt identification of key clinical signs in optimizing care outcomes. By raising the index of suspicion among pediatricians, with consideration of overall prognosis, earlier diagnosis can lead to a more holistic approach to patient- and family-centered care.