A Case Series on Genotype and Outcome of Liver Transplantation in Children with Niemann-Pick Disease Type C
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Patients
2.3. Statistics
3. Results
3.1. Demographic Data
3.2. Symptoms at Presentation
3.3. Transplantation and Diagnosis
3.4. Follow-Up
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Sundaram, S.S.; Alonso, E.M.; Narkewicz, M.R.; Zhang, S.; Squires, R.H. Characterization and Outcomes of Young Infants with Acute Liver Failure. J. Pediatr. 2011, 159, 813–818.e1. [Google Scholar] [CrossRef] [Green Version]
- Berardi, G.; Tuckfield, L.; DelVecchio, M.T.; Aronoff, S. Differential Diagnosis of Acute Liver Failure in Children: A Systematic Review. Pediatr. Gastroenterol. Hepatol. Nutr. 2020, 23, 501–510. [Google Scholar] [CrossRef] [PubMed]
- Borovsky, K.; Banc-Husu, A.M.; Saul, S.A.; Neighbors, K.; Kelly, S.; Alonso, E.M.; Taylor, S.A. Applying an Age-specific Definition to Better Characterize Etiologies and Outcomes in Neonatal Acute Liver Failure. J. Pediatr. Gastroenterol. Nutr. 2021, 73, 80–85. [Google Scholar] [CrossRef] [PubMed]
- Imrie, J.; Dasgupta, S.; Besley, G.T.; Harris, C.; Heptinstall, L.; Knight, S.; Vanier, M.T.; Fensom, A.H.; Ward, C.; Jacklin, E.; et al. The natural history of Niemann-Pick disease type C in the UK. J. Inherit. Metab. Dis. 2007, 30, 51–59. [Google Scholar] [CrossRef] [PubMed]
- Imrie, J.; Heptinstall, L.; Knight, S.; Strong, K. Observational cohort study of the natural history of Niemann-Pick disease type C in the UK: A 5-year update from the UK clinical database. BMC Neurol. 2015, 15, 257. [Google Scholar] [CrossRef] [Green Version]
- Vanier, M.T. Niemann-Pick diseases. Handb. Clin. Neurol. 2013, 113, 1717–1721. [Google Scholar] [PubMed]
- Parenti, G.; Andria, G.; Ballabio, A. Lysosomal storage diseases: From pathophysiology to therapy. Annu. Rev. Med. 2015, 66, 471–486. [Google Scholar] [CrossRef]
- Fink, J.K.; Filling-Katz, M.R.; Sokol, J.; Cogan, D.G.; Pikus, A.; Sonies, B.; Soong, B.; Pentchev, P.G.; Comly, M.E.; Brady, R.O.; et al. Clinical spectrum of Niemann-Pick disease type C. Neurology 1989, 39, 1040–1049. [Google Scholar] [CrossRef]
- Patterson, M.C.; Hendriksz, C.J.; Walterfang, M.; Sedel, F.; Vanier, M.T.; Wijburg, F. Recommendations for the diagnosis and management of Niemann–Pick disease type C: An update. Mol. Genet. Metab. 2012, 106, 330–344. [Google Scholar] [CrossRef]
- Vanier, M.T.; Gissen, P.; Bauer, P.; Coll, M.J.; Burlina, A.; Hendriksz, C.J.; Latour, P.; Goizet, C.; Welford, R.W.; Marquardt, T.; et al. Diagnostic tests for Niemann-Pick disease type C (NP-C): A critical review. Mol. Genet. Metab. 2016, 118, 244–254. [Google Scholar] [CrossRef]
- Sitarska, D.; Lugowska, A. Laboratory diagnosis of the Niemann-Pick type C disease: An inherited neurodegenerative disorder of cholesterol metabolism. Metab. Brain Dis. 2019, 34, 1253–1260. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chakrapani, A.; Gissen, P.; Kelly, D.A. Metabolic Liver Disease in the Infant and Older Child. Dis. Liver Biliary Syst. Child. 2017, 37, 289–322. [Google Scholar]
- Kumagai, T.; Terashima, H.; Uchida, H.; Fukuda, A.; Kasahara, M.; Kosuga, M.; Okuyama, T.; Tsunoda, T.; Inui, A.; Fujisawa, T.; et al. A case of Niemann-Pick disease type C with neonatal liver failure initially diagnosed as neonatal hemochromatosis. Brain Dev. 2019, 41, 460–464. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yamada, N.; Inui, A.; Sanada, Y.; Ihara, Y.; Urahashi, T.; Fukuda, A.; Sakamoto, S.; Kasahara, M.; Yoshizawa, A.; Okamoto, S.; et al. Pediatric liver transplantation for neonatal-onset Niemann-Pick disease type C: Japanese multicenter experience. Pediatr. Transplant. 2019, 23, e13462. [Google Scholar] [CrossRef] [PubMed]
- Birch, N.C.; Radio, S.; Horslen, S. Metastatic hepatocellular carcinoma in a patient with niemann-pick disease, type C. J. Pediatr. Gastroenterol. Nutr. 2003, 37, 624–626. [Google Scholar] [CrossRef] [PubMed]
- Kelly, D.A.; Portmann, B.; Mowat, A.P.; Sherlock, S.; Lake, B.D. Niemann-Pick disease type C: Diagnosis and outcome in children, with particular reference to liver disease. J. Pediatr. 1993, 123, 242–247. [Google Scholar] [CrossRef]
- Vanier, M.T.; Rodriguez-Lafrasse, C.; Rousson, R.; Gazzah, N.; Juge, M.C.; Pentchev, P.G.; Revol, A.; Louisot, P. Type C Niemann-Pick disease: Spectrum of phenotypic variation in disruption of intracellular LDL-derived cholesterol processing. Biochim. Biophys. Acta 1991, 1096, 328–337. [Google Scholar] [CrossRef]
- Carstea, E.D.; Polymeropoulos, M.H.; Parker, C.C.; Detera-Wadleigh, S.D.; O’Neill, R.R.; Patterson, M.; Goldin, E.; Xiao, H.; Straub, R.E.; Vanier, M.T. Linkage of Niemann-Pick disease type C to human chromosome 18. Proc. Natl. Acad. Sci. USA 1993, 90, 2002–2004. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vanier, M.T.; Duthel, S.; Rodriguez-Lafrasse, C.; Pentchev, P.; Carstea, E.D. Genetic heterogeneity in Niemann-Pick C disease: A study using somatic cell hybridization and linkage analysis. Am. J. Hum. Genet. 1996, 58, 118–125. [Google Scholar]
- Millat, G.; Marçais, C.; Rafi, M.A.; Yamamoto, T.; Morris, J.A.; Pentchev, P.G.; Ohno, K.; Wenger, D.A.; Vanier, M.T. Niemann-Pick C1 Disease: The I1061T Substitution Is a Frequent Mutant Allele in Patients of Western European Descent and Correlates with a Classic Juvenile Phenotype. Am. J. Hum. Genet. 1999, 65, 1321–1329. [Google Scholar] [CrossRef] [Green Version]
- Rodrigues, A.F.; Gray, R.G.; Preece, M.A.; Brown, R.; Hill, F.G.; Baumann, U.; McKiernan, P.J. The usefulness of bone marrow aspiration in the diagnosis of Niemann-Pick disease type C in infantile liver disease. Arch. Dis. Child. 2006, 91, 841–844. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ries, M.; Schaefer, E.; Luhrs, T.; Mani, L.; Kuhn, J.; Vanier, M.T.; Krummenauer, F.; Gal, A.; Beck, M.; Mengel, E. Critical assessment of chitotriosidase analysis in the rational laboratory diagnosis of children with Gaucher disease and Niemann-Pick disease type A/B and C. J. Inherit. Metab. Dis. 2006, 29, 647–652. [Google Scholar] [CrossRef] [PubMed]
Demographic Variable | Result | n |
---|---|---|
Male | 6 (67) | 9 |
Family history | ||
Consanguinity | 1 (11) | 9 |
Death among siblings | 1 (11) | 9 |
Miscarriages and termination | 2 1 (22) | 9 |
Birth | ||
Gestational age week, median (range) | 37 (32–38) | 8 2 |
Birth weight, kg, median (range) | 2.9 (2.4–3.5) | 8 2 |
Caesarean section | 1 3 (11) | 9 |
Fetal hydrops | 1 (11) | 9 |
Fetal ascites | 1 4 (11) | 9 |
Age at first clinical symptom, days, median (range) | 7 (0–37) | 9 |
Clinical presentation | ||
Jaundice | 8 (89) | 9 |
Hepatomegaly | 8 (89) | 9 |
Splenomegaly | 8 (89) | 9 |
Ascites | 6 (67) | 9 |
Respiratory distress | 5 (56) | 9 |
Hypoglycaemia | 4 (44) | 9 |
Other | 2 5 (22) | 9 |
Biochemistry at presentation, median (range) | ||
Total bilirubin, micromol/L | 277 (100–477) | 8 |
Alanine aminotransferase, U/L | 75 (10–164) | 8 |
Aspartate aminotransferase, U/L | 325 (66–531) | 8 |
Gamma glutamyl transferase, U/L | 52 (15–330) | 8 |
Prothrombine time, seconds | 46.5 (13–110) | 8 |
PT > 40 s | 5 (56) | 9 |
Albumin, g/L | 27 (13–39) | 8 |
Ammonia, µmol/L | 74 (55–176) | 6 |
Lactate, mmol/L | 2 (2–3) | 4 |
Case | Country | Sex | NPC1 Mutations | Outcome | Follow-Up Time |
---|---|---|---|---|---|
1 | Canada | M | NA 1 | No reported issues | 7 years |
2 | Canada | M | c.3229C > T and c.3182 T > C | Developmental delay, seizures and gelastic cataplexy | 13 years |
3 | Germany | F | NA 1 | Gelastic cataplexy | NA |
4 | UK | M | Heterozygeus for missense variant of NPC1 gene: Phe1207Ser in exon 24; c.3591 + 4delA in exon 23 | No reported issues | 8 years |
5 | UK | F | NA 1 | DEAD 2 | 5 years |
6 | Germany | M | NA 1 | Cognitive impairment and developmental delay | 13 years |
7 | Germany | M | Compound Heterozygote in the NPC1 gene: p.Ile1061Thr het; p.(Pro887Leu) het. | Cognitive impairment and developmental delay | 6 years |
8 | Australia | F | p.I1061T homozygote | No reported issues | 9 years |
9 | Spain | M | p.T1066N/p.T1066N | DEAD 3 | NA |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Modin, L.; Ng, V.; Gissen, P.; Raiman, J.; Pfister, E.D.; Das, A.; Santer, R.; Faghfoury, H.; Santra, S.; Baumann, U. A Case Series on Genotype and Outcome of Liver Transplantation in Children with Niemann-Pick Disease Type C. Children 2021, 8, 819. https://doi.org/10.3390/children8090819
Modin L, Ng V, Gissen P, Raiman J, Pfister ED, Das A, Santer R, Faghfoury H, Santra S, Baumann U. A Case Series on Genotype and Outcome of Liver Transplantation in Children with Niemann-Pick Disease Type C. Children. 2021; 8(9):819. https://doi.org/10.3390/children8090819
Chicago/Turabian StyleModin, Line, Vicky Ng, Paul Gissen, Julian Raiman, Eva Doreen Pfister, Anibh Das, René Santer, Hanna Faghfoury, Saikat Santra, and Ulrich Baumann. 2021. "A Case Series on Genotype and Outcome of Liver Transplantation in Children with Niemann-Pick Disease Type C" Children 8, no. 9: 819. https://doi.org/10.3390/children8090819