Niemann-Pick DiseaseBy Heather Reymunde
Outlineu Introduction to Niemann-Pick
u Etiology
u Genetic Factor
u Nutrition Component
u Intervention
u Conclusion
What is Niemann-Pick?• Group of genetically inherited diseases
• Lipid Metabolism Disorder (Lysosomal Storage Disease)
• Prevalence
- 4 subtypes
Type A/B: Accumulation of sphingomyelin within the organs and CNS
Type A:
- Dx: Infancy – 3 years, Death within 3 years of diagnosis
- Neurological Function
- Physical Manifestations: FTT
- Chronic features: n/a
Type B:
- Dx: mid-childhood but survive through adulthood
- Non-Neurological
- Physical manifestations: short stature and slowed bone mineralization (McGovern & Schuchman2014).
- Chronic features: lung infections and low number of platelets
Word of the Day
*Sphingolipid*
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What is Niemann-Pick?Type C1/C2: Different pathology than A & B
Accumulation of cholesterol absorption in the intestinal tract
Increased synthesis of endogenous cholesterol & Increased absorption
(via 3-hydroxy-3-methyl glutaryl co-enzyme A reductase) (Tomkin, 2015).
• Dx
• Childhood through Adulthood
• Develop into adulthood
• Deteriorating quality of life
• Physical Manifestations
• Ataxia & dystonia
• Liver disease and pulmonary disease
• Dysphagia & dysphasia
http://www.niemann-pick-c.com/HCP/Symptoms/Symptomatic-manifestations-of-Niemann-Pick-type-C-disease
Etiologyu Autosomal recessive disease
u Type A: Mutations in the SMPD1 Gene
u Ashkenazi Jewish Population
u Maternal Expression
u Type B: Mutations in the SMPD1 Gene
u Heteroallelic Variation
u Type C1: Mutation in the NPC1 Gene on Chromosome 18
u Type C2: Mutation in the NPC2 Gene on Chromosome 14
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Genetic Factors- Type A & B
u Type A
u Identifiable SNP’s (23andme)
u Prenatal Testing/Infancy
Gene Phenotype Type/SNP Genotype Risk
SMPD1 NPD A i4000381/L302P CC
SMPD1 NPD A i4000383/fsP330 n/a
SMPD1 NPD A i4000430/R496L TT
Gene Phenotype Type/SNP Genotype Risk
SMPD1 NPD B i4000430/R496L Heterozygous Mutationu Type B
u Heteroallelic R496L
u 3 base deletion
u Detectable in early childhood
(Genetics Home Reference, 2018)
Genetic Factors- NPD Type C
Both forms of Type C are *diagnosable* by the Sanger Sequencing of the NPC gene.
u polymerase chain reaction (PCR) to target the 30 coding exons, and intron-exon boundaries, of the NPC1 and NPC2 genes.
u Next-generation sequencing available
u *Not all variations have been documented to date
Gene Phenotype Type/SNP Genotype Risk
NCPC1 NPD C1 rs1631685
rs1788799
Rs18050810
I1061T
Heterozygous Mutation
Gene Phenotype Type/SNP Genotype Risk
NCPC2 NPD C2 Rs8008540
Rs917394
Homozygous Mutationu Type C2
u Chromosome 14
u Homoallelic
u Dx at any age
u Type C1
u Chromosome 18
u Heteroallelic
u Dx at any age
u Proposed 40 SNPs (Genetics Home Reference, 2018)
NPC Suspicion Tool
(Papandreou& Gissen, 2016)
Nutrition Componentu Ultimate Goal: Holistic Care
u Management of Care in the Feeding Team:
u GI (Constipation, GERD)
u Speech/Oral Pathology
u OT/PT
u Genetic Counseling
u Visits with an RDN!
Role of an RDN as part of the care team: Provide MNT and Improve Quality of Life
u Type A: Managing FTT, providing prescribed nourishment and nutrient delivery
u Type B: Proper Growth, feeding habits, monitor routine bloodwork
u Type C: Weight Maintenance, Altered Caloric Needs, Nutrient Delivery
https://abbotteqip.com
Nutrition Intervention” Dietary Rx
u No known diets to prevent or manage disease
For a adult patient with NPD B/C and ability to self-feeding:
u Adequate intake of Energy-dense (plant-based) foods
u Lower cholesterol food
u High fruits and vegetable intake
u Proper Hydration
u Calcium and Vitamin E supplementation
u Cooking with Spices
Conclusionu NPD has no current cure or medical nutrition therapy plan
u KEY: Early detection by of advancement screening and profiling
u RDN can provide a better quality of life to a patient with NPD by:
u frequent assessment of caloric intake
u delivery of nutrients
u low cholesterol and supplementation
u Prevention of Malnutrition
ReferencesCamp, K. M., & Trujillo, E. (2014). Position of the academy of nutrition and dietetics: Nutritional genomics. Journal of the Academy of Nutrition and Dietetics, 114(2), 299–312. https://doi.org/10.1016/j.jand.2013.12.001
Genetics Home Reference. (2018). Genetics home reference. 2015 Feb 2. Retrieved from http://ghr.nlm.nih.gov/condition/retinoblastoma
Grafft, C. A., Fervenza, F. C., & Semret, M. H. (2009). Renal involvement in Neimann-Pick Disease. NDT Plus, 2(6), 448–451. https://doi.org/10.1093/ndtplus/sfp101
Jaffe, A. C. (2011). Failure to Thrive: Current Clinical Concepts. Pediatrics in Review, 32(3), 100–108. https://doi.org/10.1542/pir.32-3-100
Lee, H., Lee, J. K., Park, M. H., Hong, Y. R., Marti, H. H., Kim, H., … Jin, H. K. (2014). Pathological roles of the VEGF/SphK pathway in Niemann-Pick type C neurons. Nature Communications, 5(May), 1–17. https://doi.org/10.1038/ncomms6514
Madra, M., & Sturley, S. (2011). Niemann–Pick type C pathogenesis and treatment: from statins to sugars. Clinical Lipidology, 5(3), 387–395. https://doi.org/10.2217/clp.10.19.Niemann
Mcgovern, M. M., & Schuchman, E. H. (2014). Acid Sphingomyelinase Deficiency. GeneReviews (R), 1–16. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK1370/
McKay Bounford, K., & Gissen, P. (2014). Genetic and laboratory diagnostic approach in Niemann Pick disease type C. Journal of Neurology, 261(SUPPL. 2), 569–575. https://doi.org/10.1007/s00415-014-7386-8
National Center for Biotechnology Information. (2014). Niemann-Pick disease. SNPedia, 4000381(November).
National Institute of Health. (2018). The Human Genome Project. The Human Genome Project.
Papandreou, A., & Gissen, P. (2016). Diagnostic workup and management of patients with suspected Niemann-Pick type C disease. Therapeutic Advances in Neurological Disorders, 9(3), 216–229. https://doi.org/10.1177/1756285616635964
Spataro, N., Rodríguez, J. A., Navarro, A., & Bosch, E. (2017). Properties of human disease genes and the role of genes linked to Mendelian disorders in complex disease aetiology. Human Molecular Genetics, 26(3), 489–500. https://doi.org/10.1093/hmg/ddw405
Tomkin, G. H. (2015). Dyslipidaemia of diabetes and the intestine. World Journal of Diabetes, 6(7), 970. https://doi.org/10.4239/wjd.v6.i7.970
United States Department of Agriculture. (2016). Dietary Guideline Fruit and Vegetable Recommendations. Choose My Plate Website, 50–51. Retrieved from http://www.choosemyplate.gov/grains
Yarr, J., Paterson, A., & Lang, T. (2015). Niemann-Pick Disease ( type B ). Eurorad, 0.