Chronic arthritis in children is widely associated with juvenile idiopathic arthritis (JIA); however, several rare monogenic disorders may mimic its clinical presentation. Misdiagnosis can result in unnecessary immunosuppressive treatment and delay appropriate care. This study aimed to share our experience with monogenic disorders presenting as chronic arthritis and highlight their distinguishing clinical and imaging features. This retrospective cohort study included patients initially suspected of having JIA who were later diagnosed with a monogenic disorder. Clinical, laboratory, imaging, and genetic data were also collected and evaluated. Among the 25 patients, the most frequent diagnoses were progressive pseudorheumatoid dysplasia (PPRD; n = 12) and camptodactyly arthropathy-coxa vara-pericarditis (CACP) syndrome (n = 8). Other diagnoses included mucolipidosis type III gamma, primary hypertrophic osteoarthropathy (PHO), and multicentric carpotarsal osteolysis (MCTO). While all PPRD and CACP patients had biallelic pathogenic variants in CCN6 and PRG4, respectively, PHO and MCTO were associated with monoallelic mutations. Common misdiagnoses included polyarticular JIA, leading to the inappropriate use of methotrexate or biologic agents. Several monogenic disorders can mimic JIA in pediatric patients, leading to diagnostic challenges. Clinical features, such as camptodactyly, skeletal deformities, digital clubbing, median nerve neuropathy, and poor response to treatment should prompt further evaluation, including genetic testing. Increased awareness and early recognition of these conditions are crucial to avoid unnecessary immunosuppression and improve patient outcomes. • Several rare monogenic disorders can clinically mimic JIA and misdiagnosis of these monogenic mimickers may lead to inappropriate immunosuppressive treatment and delayed appropriate care. • This study presents a real-world single-center data that systematically characterizes five distinct monogenic disorders mimicking JIA. • Findings emphasize the importance of early suspicion, especially in cases with symmetrical interphalangeal involvement (PPRD), camptodactyly with hip deformity (CACP), or osteolysis with renal/facial anomalies (MCTO), to avoid unnecessary immunosuppression.

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. 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. 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.

Lysosomal storage diseases are a group of rare hereditary metabolic diseases. Due to a deficiency of lysosomal enzymes, complex substrates accumulate in the lysosomes of various organs. Depending on the affected enzyme, this results in clinically variable and chronic progressive multiorgan diseases. Diagnosis is often delayed. As clinical symptoms include the musculoskeletal system, an awareness of lysosomal storage diseases is of relevance to (pediatric) rheumatologists. This article is focused on Mucopolysaccharidosis type I‑S, Mucolipidosis type III, Gaucher disease and Fabry disease. When suspecting a lysosomal storage disease, enzyme activity should be determined in dried blood spots or leukocytes. For some diseases, specific biomarkers can additionally be analyzed. Diagnosis should be confirmed by genetic testing. As causal treatment options are available for three of the presented diseases, a timely diagnosis is very important. Lysosomale Speicherkrankheiten sind eine Gruppe seltener hereditärer Stoffwechselkrankheiten. Durch einen Mangel lysosomaler Enzyme akkumulieren komplexe Substrate in den Lysosomen verschiedener Organe. Abhängig vom betroffenen Enzym resultiert dies in klinisch variablen und chronisch progredienten Multiorgankrankheiten. Die Diagnosestellung erfolgt oft mit großer zeitlicher Verzögerung. Die klinische Symptomatik kann auch den Bewegungsapparat betreffen, weshalb eine grundlegende Kenntnis über lysosomale Speicherkrankheiten in der (kinder)rheumatologischen Praxis von Relevanz ist. Exemplarisch werden hier die Mukopolysaccharidose Typ I‑S, die Mukolipidose Typ III, der Morbus Gaucher und der Morbus Fabry vorgestellt. Bei Verdacht auf eine lysosomale Speicherkrankheit ist eine Bestimmung der Enzymaktivität im Trockenblut oder in Leukozyten angezeigt, teilweise lassen sich auch krankheitsspezifische Biomarker bestimmen. Zur Diagnosesicherung wird eine molekulargenetische Untersuchung ergänzt. Für 3 der hier vorgestellten Erkrankungen stehen kausale Therapien zur Verfügung, sodass der frühzeitigen Diagnosestellung eine große Bedeutung zukommt.

We describe the case of a 47-year-old man referred to a retinal clinic and diagnosed with late-onset retinitis pigmentosa. Surprisingly, genetic testing revealed compound heterozygous pathogenic variants in GNPTG, leading to the diagnosis of the autosomal recessive lysosomal storage disorder mucolipidosis type III gamma. Mucolipidosis type III gamma is typically diagnosed during childhood due to symptoms relating to skeletal dysplasia. Retinal dystrophy is not a common phenotypic feature. Ophthalmologic examination was consistent with a mild form of retinitis pigmentosa and included fundus photography, measurement of best-corrected visual acuity, optical coherence tomography, electroretinogram and visual field testing. Extraocular findings included joint restriction and pains from an early age leading to bilateral hip replacement by age 30, aortic insufficiency, and hypertension. Genetic analysis was performed by whole genome sequencing filtered for a gene panel of 325 genes associated with retinal disease. Two compound heterozygous pathogenic variants were identified in GNPTG, c.347_349del and c.607dup. The diagnosis of mucolipidosis type III gamma was confirmed biochemically by measurement of increased activities of specific lysosomal enzymes in plasma. To our knowledge this is the first description of retinitis pigmentosa caused by compound heterozygous variants in GNPTG, providing further indications that late-onset retinal dystrophy is part of the phenotypic spectrum of mucolipidosis type III gamma.