Background: Mucopolysaccharidosis type III (Sanfilippo syndrome) is a rare lysosomal storage disorder characterised by progressive neurodegeneration due to impaired degradation of heparan sulphate. Early symptoms may overlap with neurodevelopmental conditions such as autism spectrum disorder (ASD), often leading to delayed diagnosis.

Case Presentation: We report the case of a 9-year-old girl initially diagnosed with ASD at 3 years of age. Early developmental milestones included independent walking, singing, and functional communication. Over time, she exhibited significant neurodevelopmental regression, including loss of expressive language, progressive motor decline resulting in inability to walk, and onset of epilepsy. Additional features included behavioural changes with marked irritability, sleep disturbances, and the development of coarse facial features and thick hair. Given the pattern of regression and evolving phenotype, a metabolic evaluation was undertaken. Urinary glycosaminoglycan analysis demonstrated increased excretion of heparan sulphate. Subsequent enzymatic testing in leukocytes confirmed deficient sulphamidase activity, consistent with a diagnosis of mucopolysaccharidosis type IIIA.

Discussion: This case highlights the diagnostic challenge posed by Sanfilippo syndrome, particularly in patients initially presenting with features suggestive of ASD. Progressive regression, emergence of neurological symptoms such as epilepsy, and somatic changes should prompt reconsideration of the diagnosis and evaluation for underlying metabolic disorders. Early recognition is critical for appropriate management, genetic counselling, and consideration of emerging therapies.

Conclusion: Clinicians should maintain a high index of suspicion for lysosomal storage disorders in children with ASD who demonstrate developmental regression and additional neurological or somatic features. This case underscores the importance of revisiting diagnoses in the context of evolving clinical presentations.

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