Hand stiffness not only a rheumatological sign: A case of early onset mucolipidosis III-gamma with literature review.

BACKGROUND: Mucolipidosis (ML) is a rare autosomal recessive lysosomal disorder with variable onset and severity: MLII, characterized by early onset and rapid progression, and MLIII, milder with late onset and prolonged survival. ML is due to mutations in the Golgi enzyme uridine diphosphate-N-acetylglucosamine-1-phosphotransferase, whose subunits are encoded by GNPTAB and GNPTG genes. This report presents a particular case of infantile early-onset MLIII-gamma and emphasizes that articular manifestations can be a sign of a metabolic disease rather than a rheumatological or orthopedic one.

CASE REPORT: A 5.7-years-old girl presented with progressive hand stiffness and joint pain, exhibiting symptoms from 6 months of age. She displayed claw-hand deformity and joint stiffness but normal growth and neurodevelopment. Biochemical testing revealed normal activities of alpha-L-iduronidase and arylsulfatase-B in leukocytes, excluding mucopolysaccharidosis I and VI, while beta-hexosaminidase and alpha-L-fucosidase activities in plasma were elevated, suggesting ML. Genetic analysis of GNPTAB and GNPTG identified two pathogenic variants in the GNPTG gene, confirming MLIII-gamma diagnosis. Despite early onset, the patient exhibited a less severe skeletal phenotype and showed mild cardiac and ocular involvement, occasionally described in classic MLIII-gamma.

DISCUSSION: The natural history of MLIII remains poorly understood and mainly based on sporadic case reports/series. Our case presents a typical MLIII-gamma phenotype but with an unexpectedly early onset, expanding the clinical spectrum of this disease. It emphasizes the need for increased awareness among pediatric rheumatologists regarding metabolic disorders. Further case studies are essential to enhance understanding and improve diagnostic and therapeutic approaches for ML.