Kara Cemre, Köse Engin, Eminoğlu Fatma Tuba
Department of Pediatrics, Ankara University Faculty of Medicine, Ankara, Türkiye.
Department of Pediatric Metabolism and Ankara University Rare Diseases Application and Research Center, Ankara University Faculty of Medicine, Ankara, Türkiye.
J Pediatr Endocrinol Metab. 2025 Jan 10;38(5):539-545. doi: 10.1515/jpem-2024-0530. Print 2025 May 26.
Niemann-Pick type C (NPC) is a rare, autosomal recessive, neurodegenerative disorder caused by biallelic pathogenic variants in the or genes, leading to lysosomal lipid accumulation. NPC has an incidence of 1 in 100,000 live births and presents with a wide range of symptoms affecting visceral organs and the central nervous system. We aim to describe the diverse clinical presentations of NPC through case studies.
We report seven NPC patients from five families, showcasing the variability in clinical manifestations. The most common finding was hepatosplenomegaly (70 %), followed by prolonged jaundice (57 %) and neonatal cholestasis. Pulmonary alveolar proteinosis (PAP) was observed in three patients with biallelic pathogenic variants in the gene. Neurological symptoms, including vertical gaze palsy and epilepsy, were noted in patients with juvenile onset form. Genetic analyses identified a novel homozygous c.315del (p.Thr106ProfsTer5) variant in the gene, associated with early infantile onset.
NPC presents with diverse clinical findings across ages. Early hepatic symptoms in infants and neuropsychiatric issues in older patients warrant a high index of suspicion for NPC in such cases. A multidisciplinary approach is crucial for patient management, and further research is needed to clarify genotype-phenotype relationships in NPC.
尼曼-匹克C型（NPC）是一种罕见的常染色体隐性神经退行性疾病，由NPC1或NPC2基因的双等位基因致病性变异引起，导致溶酶体脂质蓄积。NPC的发病率为每10万活产中有1例，表现出影响内脏器官和中枢神经系统的广泛症状。我们旨在通过病例研究描述NPC的多种临床表现。
我们报告了来自五个家庭的7例NPC患者，展示了临床表现的变异性。最常见的发现是肝脾肿大（70%），其次是长期黄疸（57%）和新生儿胆汁淤积。在3例NPC2基因双等位基因致病性变异的患者中观察到肺泡蛋白沉积症（PAP）。青少年发病型患者出现神经症状，包括垂直凝视麻痹和癫痫。基因分析在NPC1基因中鉴定出一种新的纯合c.315del（p.Thr106ProfsTer5）变异，与早发型婴儿型相关。
NPC在各年龄段均有不同的临床表现。婴儿期的早期肝脏症状和老年患者的神经精神问题在此类病例中需要高度怀疑NPC。多学科方法对患者管理至关重要，需要进一步研究以阐明NPC的基因型-表型关系。
