Peculiarities of the course of Niemann-Pick disease, type C, in early childhood as exemplified by clinical observation

We present a clinical case of Niemann—Pick disease type C, caused by mutations c3182T>C and 2279_2281delTCT in a compound heterozygous state, in a child 4 years 10 months old. The onset of the disease at the age of 1 month 11 days in the form of hemorrhagic syndrome, hyperbilirubinemia, cholestasis, hypertransaminasemia was initially regarded as a manifestation of hemorrhagic disease of the newborn. Persistent hepatosplenomegaly required long-term observation and consideration in the differential diagnostic aspect of hepatitis of various etiologies and lysosomal storage diseases. The duration of diagnosis is associated with the slow progression of nonspecific neurovisceral manifestations and the difficulty of interpreting neurological symptoms in infancy and early childhood. Damage to the nervous system was represented at the initial stages of observation by diffuse muscle hypotonia, which did not interfere with the timely development of motor skills during the first year of life. As the child grows and develops, cognitive deficits and statolocomotor disorders become dominant in the clinical picture; negative dynamics are expressed in the progression of cerebellar insufficiency. At the same time, visceral manifestations tended to be stable during the use of substrate-reducing therapy with the drug miglustat, which currently allows us to count on a favorable prognosis for the child’s life and longer-term maintenance of residual functions of the nervous system.

In the early stages of Niemann—Pick disease type C, with unformed multiple organ lesions, the absence of characteristic changes in the fundus, the nonspecific nature of the clinical picture and changes in laboratory parameters, the dynamics of neuropsychic development and the characteristics of the neurological status of the child acquire important diagnostic significance and justify the use of molecular research methods. Considering that the goal of using targeted therapy for Niemann—Pick disease type C is to stabilize degenerative processes and slow down the progression of clinical manifestations, reducing the time to diagnose the disease is a key factor determining the prognosis.

1. Berry-Kravis E. Niemann-Pick Disease, Type C: Diagnosis, Management and Disease-Targeted Therapies in Development. Semin Pediatr Neurol. 2021; 37: 100879. DOI: 10.1016/j.spen.2021.100879

2. Hosseini K., Fallahi J., Razban V., Sirat R.Z., Varasteh M., Tarhriz V. Overview of clinical, molecular, and therapeutic features of Niemann-Pick disease (types A, B, and C): Focus on therapeutic approaches. Cell Biochem Funct. 2024; 42(4): e4028. DOI: 10.1002/cbf.4028

3. Las Heras M., Szenfeld B., Ballout R.A., Buratti E., Zanlungo S., Dardis A. et al. Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine. NPJ Genom Med. 2023;8(1):21. DOI: 10.1038/s41525-023-00365-w

4. Guatibonza Moreno P., Pardo L.M., Pereira C., Schroeder S., Vagiri D., Almeida L.S., et al. At a glance: the largest Niemann-Pick type C1 cohort with 602 patients diagnosed over 15 years. Eur J Hum Genet. 2023;31(10):1108-1116. DOI: 10.1038/s41431-023-01408-7

5. Tao C., Zhao M., Zhang X., Hao J., Huo Q., Sun J. et al. Novel compound heterozygous mutations of the NPC1 gene associated with Niemann-pick disease type C: a case report and review of the literature. BMC Infect Dis. 2024;24(1):145. DOI: 10.1186/s12879-024-09025-5

6. Yañez M.J., Marín T., Balboa E., Klein A.D., Alvarez A.R., Zanlungo S. Finding pathogenic commonalities between Niemann-Pick type C and other lysosomal storage disorders: Opportunities for shared therapeutic interventions. Biochim Biophys Acta Mol Basis Dis. 2020;1866(10):165875. DOI: 10.1016/j.bbadis.2020.165875

7. Sitarska D., Ługowska A. Laboratory diagnosis of the Niemann-Pick type C disease: an inherited neurodegenerative disorder of cholesterol metabolism. Metab Brain Dis. 2019;34(5):1253-1260. DOI:10.1007/s11011-019-00445-w

8. Kresojević N., Dobričić V., Lukić M.J., Tomić A., Petrović I., Dragašević N. et al. Genetic and phenotypic variability in adult patients with Niemann Pick type C from Serbia: single-center experience. J Neurol. 2022;269(6):3167-3174. DOI: 10.1007/s00415-021-10918-7

9. Mengel E., Pineda M., Hendriksz C.J., Walterfang M., Torres J.V., Kolb S.A. Differences in Niemann-Pick disease Type C symptomatology observed in patients of different ages. Mol Genet Metab. 2017;120(3):180-189. DOI: 10.1016/j.ymgme.2016.12.003

10. Dos Santos Mendes R., do Valle D.A., Dos Santos Bara T., Furlin V., da Silva Zeny M., Schmitz Ferreira Santos M.L. et al. Clinical, genotypic, and neuropsychological profile in a series of patients with Niemann-Pick type C disease. Front Neurol. 2025;16:1542310. DOI: 10.3389/fneur.2025.1542310

11. Seker Yilmaz B., Baruteau J., Rahim A.A., Gissen P. Clinical and Molecular Features of Early Infantile Niemann Pick Type C Disease. Int J Mol Sci. 2020;21(14):5059. DOI: 10.3390/ijms21145059

12. Fedoseeva I.F., Poponnikova T.V., Pinevich O.S. Myopathy in glycogen storage disease type IV: case report of a family. Byulleten’ sibirskoj mediciny. 2024;23(3):172-177. (in Russ.) DOI: 10.20538/1682-0363-2024-3-172-177

13. Fedoseeva I.F., Goncharenko A.V., Poponnikova T.V., Goncharenko V.A. Opsoclonus-Myoclonus Syndrome in Children: Modern Data. Voprosy sovremennoj pediatrii. 2025; 24(1): 6–12. (in Russ.) DOI: 10.15690/vsp.v24i1.2848

14. Rakhmaeva R.F., Sageeva G.I., Artykova N.A., Mingacheva N.R., Danilaeva N.M., Kamalova A.A. Perinatal form of Niemann-Pick disease type C on the background of substrate-reducing therapy. Rossiyskiy Vestnik Perinatologii i Pediatrii. 2023;68(5):73-77. (in Russ.) DOI: 10.21508/1027-4065-2023-68-5-73-77

15. Mingacheva Nailya R., Kamalova Aelita A., Artykova Nargis A., Rakhmaeva Razilya F., Sageeva Gulnara I. Case report of the perinatal form of Nieman-Pick disease type С against the backdrop of pathogenetic off-label therapy. Pediatricheskaya farmakologiya. 2024;21(2):126–130. (in Russ.) DOI:10.15690/pf.v21i2.2746

16. Zhang H., Xiong H., Wei C., Yi M., Che Y., Zhuo J. et al. Evaluation of the safety and efficacy of miglustat for the treatment of Chinese patients with Niemann-Pick disease type C: A prospective, open-label, single-arm, phase IV trial. Intractable Rare Dis Res. 2024;13(4):227-235. DOI: 10.5582/irdr.2024.01056

17. Freihuber C., Dahmani-Rabehi B., Brassier A., Broué P., Cances C., Chabrol B. et al. Effects of miglustat therapy on neurological disorder and survival in early-infantile Niemann-Pick disease type C: a national French retrospective study. Orphanet J Rare Dis. 2023;18(1):204. DOI: 10.1186/s13023-023-02804-4