Mucolipidosis Type III: A Hidden Challenge in the Differential Diagnosis of Rheumatological Disorders

OBJECTIVE: Mucolipidosis type III (ML-III) alpha/beta and gamma are uncommon lysosomal storage diseases caused by a partial deficiency of the N-acetylglucosaminyl-1-phosphotransferase enzyme. Biallelic mutations in the GNPTAB gene are responsible for ML-III alpha/beta, whereas mutations in GNPTG lead to ML-III gamma. This study aims to thoroughly investigate the clinical manifestations and diagnostic clues of ML-III, with the goal of preventing misdiagnosis and delays in diagnosis. METHODS: A retrospective review was conducted of all patients referred to the Pediatric Metabolism Department between 2010 and 2022 due to joint stiffness and/or pain, with a total of 192 patients evaluated during this period. The clinical, laboratory, radiological, and genetic data of patients diagnosed with ML-III were reviewed in detail. RESULTS: Six patients (3.1%) from the cohort of 192 were diagnosed with ML-III. The median age of these patients at symptom onset was 2.75 years (min-max: 1.2-11.5 years). The initial finding of all patients was stiffness of finger joints. Five patients were misdiagnosed before admission, and the median age at diagnosis was 12 years (min-max: 5-35 years). The median delay in diagnosis was 6.5 years (min-max: 3-24 years). Neither ML-III alpha/beta nor ML-III gamma patients had psychomotor retardation. The patients' ages ranged from 8.6 to 38 years. CONCLUSION: The ML-III's clinical findings can lead to misdiagnoses, such as rheumatological disorders. Heightened awareness could prompt earlier detection, underlining the importance of thorough evaluations for all patients with joint-related presentations.