Objective:

We describe a case of a 17-month-old typically developing child presenting with new onset seizures and developmental regression followed by progressive hypotonia, limb spasticity and dyskinesia found to have both autoimmune encephalitis and mucopolysaccharidosis type IIIa. This case highlights the importance of considering multiple concurrent diagnoses in atypical patient presentations.  

Background:

 A 17-month-old typically developing child presented with new onset, difficult to control focal seizures, requiring trial of two anti-seizure medications. Over the next six weeks, the patient developed significant regression including inability to feed self, loss of receptive and expressive language, as well as profound and progressive truncal hypotonia, unilateral limb spasticity.  Initial imaging with MRI brain with spectroscopy were normal. Lumbar puncture revealed elevated CSF protein, otherwise within normal limits. Serum and CSF testing returned highly positive for anti-NMDA receptor antibody. Whole exome sequencing was obtained during workup given significant developmental regression and refractory seizures, which returned with a variant of unknown significance (VUS) in the SGSH gene. This was later re-classified as pathogenic based on confirmatory metabolic testing, providing an additional diagnosis of mucopolysaccharidosis type IIIa.  The patient was treated with high-dose steroids and intravenous immunoglobulin and is receiving monthly IVIG, with some improvement of seizures and dyskinesia. However, hypotonia and developmental regression continue to progress, despite immunological and supportive therapies, most likely attributable to MPSIIIa. Repeat imaging revealed nonspecific temporal lobe gliosis and global volume loss. 

Design/Methods:

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Results:

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Conclusions:

As clinicians are often tempted to find a single unifying diagnosis, this case highlights the importance of considering multiple concurrent diagnoses in a patient with complex or atypical presentation.  Additionally, with the emergence of widely-available genetic testing, it is important to carefully evaluate variants of unknown significance, especially when treatment and/or prognosis differ greatly based on confirmation of diagnosis.