La Rosa Alessandro, Pepe Alessia, Tappino Barbara, Corsolini Fabio, Chiaro Andrea, Madeo Annalisa
Paediatric Gastroenterology and Digestive Endoscopy Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.
Mol Genet Metab Rep. 2025 Aug 13;44:101246. doi: 10.1016/j.ymgmr.2025.101246. eCollection 2025 Sep.
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--acetylglucosamine-1-phosphotransferase, whose subunits are encoded by and 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 and identified two pathogenic variants in the 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.
黏脂贮积症（ML）是一种罕见的常染色体隐性溶酶体疾病，起病和严重程度各异：MLII起病早且进展迅速，MLIII症状较轻，起病晚且生存期延长。ML是由高尔基体酶尿苷二磷酸 - N - 乙酰葡糖胺 - 1 - 磷酸转移酶的突变引起的，其亚基由 和 基因编码。本报告介绍了一例婴儿期早发性MLIII - γ的特殊病例，并强调关节表现可能是代谢性疾病的体征，而非风湿性或骨科疾病的体征。
一名5.7岁女孩自6个月大起出现进行性手部僵硬和关节疼痛。她表现出爪形手畸形和关节僵硬，但生长和神经发育正常。生化检测显示白细胞中α - L - 艾杜糖醛酸酶和芳基硫酸酯酶 - B的活性正常，排除了黏多糖贮积症I和VI，而血浆中β - 己糖胺酶和α - L - 岩藻糖苷酶的活性升高，提示为ML。对 和 的基因分析在 基因中鉴定出两个致病变异，确诊为MLIII - γ。尽管起病早，但该患者的骨骼表型较轻，且有轻度心脏和眼部受累，这在经典的MLIII - γ中偶尔会出现。
MLIII的自然病史仍知之甚少，主要基于散发病例报告/系列。我们的病例呈现出典型的MLIII - γ表型，但起病出乎意料地早，扩展了该疾病的临床谱。这强调了儿科风湿病学家需要提高对代谢性疾病的认识。进一步的病例研究对于增强对ML的理解以及改善其诊断和治疗方法至关重要。
