12
Niemann-Pick Disease By Heather Reymunde

Niemann-Pick Disease - HEATHER REYMUNDE WITTMER€¦ · National Center for Biotechnology Information. (2014). Niemann-Pick disease. SNPedia, 4000381(November). National Institute

  • Upload
    others

  • View
    3

  • Download
    0

Embed Size (px)

Citation preview

Page 1: Niemann-Pick Disease - HEATHER REYMUNDE WITTMER€¦ · National Center for Biotechnology Information. (2014). Niemann-Pick disease. SNPedia, 4000381(November). National Institute

Niemann-Pick DiseaseBy Heather Reymunde

Page 2: Niemann-Pick Disease - HEATHER REYMUNDE WITTMER€¦ · National Center for Biotechnology Information. (2014). Niemann-Pick disease. SNPedia, 4000381(November). National Institute

Outlineu Introduction to Niemann-Pick

u Etiology

u Genetic Factor

u Nutrition Component

u Intervention

u Conclusion

Page 3: Niemann-Pick Disease - HEATHER REYMUNDE WITTMER€¦ · National Center for Biotechnology Information. (2014). Niemann-Pick disease. SNPedia, 4000381(November). National Institute

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*

htt

ps:

//en.w

ikip

edia

.org

/wik

i/Sp

hin

golipid

Page 4: Niemann-Pick Disease - HEATHER REYMUNDE WITTMER€¦ · National Center for Biotechnology Information. (2014). Niemann-Pick disease. SNPedia, 4000381(November). National Institute

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

Page 5: Niemann-Pick Disease - HEATHER REYMUNDE WITTMER€¦ · National Center for Biotechnology Information. (2014). Niemann-Pick disease. SNPedia, 4000381(November). National Institute

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

http

s://

heal

thja

de.c

om/n

iem

ann-

pick

/

Page 6: Niemann-Pick Disease - HEATHER REYMUNDE WITTMER€¦ · National Center for Biotechnology Information. (2014). Niemann-Pick disease. SNPedia, 4000381(November). National Institute

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)

Page 7: Niemann-Pick Disease - HEATHER REYMUNDE WITTMER€¦ · National Center for Biotechnology Information. (2014). Niemann-Pick disease. SNPedia, 4000381(November). National Institute

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)

Page 8: Niemann-Pick Disease - HEATHER REYMUNDE WITTMER€¦ · National Center for Biotechnology Information. (2014). Niemann-Pick disease. SNPedia, 4000381(November). National Institute

NPC Suspicion Tool

(Papandreou& Gissen, 2016)

Page 9: Niemann-Pick Disease - HEATHER REYMUNDE WITTMER€¦ · National Center for Biotechnology Information. (2014). Niemann-Pick disease. SNPedia, 4000381(November). National Institute

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

Page 10: Niemann-Pick Disease - HEATHER REYMUNDE WITTMER€¦ · National Center for Biotechnology Information. (2014). Niemann-Pick disease. SNPedia, 4000381(November). National Institute

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

Page 11: Niemann-Pick Disease - HEATHER REYMUNDE WITTMER€¦ · National Center for Biotechnology Information. (2014). Niemann-Pick disease. SNPedia, 4000381(November). National Institute

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

Page 12: Niemann-Pick Disease - HEATHER REYMUNDE WITTMER€¦ · National Center for Biotechnology Information. (2014). Niemann-Pick disease. SNPedia, 4000381(November). National Institute

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.