NIEMANN PICK DISEASE

(NPD)
Presented by
J.LIVI CHRIST- 21B218
K.R.SUNIL SESHADRI -22B431
M.HARI PRASAD -22B434
INTRODUCTION:
• Niemann-Pick disease is an genetic disorder which is caused by
mutations in specific genes that are involved in the metabolism of lipids,
particularly cholesterol and sphingomyelin.
• A lysosomal storage disease caused by acid sphingomyelinase deficiency
(ASMD), which catalyzes the hydrolysis of sphingomyelin (SM) to
ceramide and phosphocholine.
• As a result, SM and its precursor lipids begin to accumulate in
lysosomes, mainly in macrophages.
• These lipid-laden macrophages deposit in the liver, spleen, lungs, and
brain causing hepatosplenomegaly, lung disease, and neurologic
symptoms such as intellectual disability.
INHERITANCE PATTERN:

• Niemann pick disease is an autosomal

recessive pattern of inheritance
• Both alleles of the gene must be
mutated in such a way that function is
impaired.
• If both parents are carriers, there is a
25% chance for an affected child with
each pregnancy.
TYPES OF NIEMANN PICK DISEASE:
• Different types of Niemann-Pick disease are caused by mutations in
different genes, leading to distinct biochemical abnormalities and
clinical manifestations.
• Types of Niemann-pick disease
1.Type A
2.Type B
3.Type C
OVERVIEW
SYMPTOMS
1.Niemann-Pick Type A (NPA) is characterized by severe neurological
regression, hepatosplenomegaly, and respiratory problems, typically
leading to death in early childhood.
2.Type B (NPB) presents with hepatosplenomegaly, respiratory issues,
delayed growth, and some neurological involvement but typically less
than NPA.
3.Type C (NPC) manifests with progressive neurological symptoms,
hepatosplenomegaly,dysphagia(Feeding difficulties),and a range of
other neurological and systemic manifestations.
TYPES OF GENETIC MUTATIONS:
1.Niemann-Pick type A (NPA):
This type is caused by mutations in the SMPD1 gene,
which is located on chromosome 11.This leads to a deficiency of the
enzyme acid sphingomyelinase.
2.Niemann-Pick type B (NPB):
Also caused by mutations in the SMPD1 gene which is
located on chromosome 11, but individuals with Niemann-Pick type B
have residual enzyme activity, resulting in less severe symptoms
compared to type A.
3.Niemann-Pick type C (NPC):
This type is caused by mutations in either the NPC1
gene which is located on chromosome 18 or NPC2 gene which is
located on chromosome 14.These genes are involved in the transport of
lipids within cells.
DIAGNOSIS:
1. Niemann-Pick Type A (NPA):
• Enzyme assays can measure the activity of acid sphingomyelinase, which is
deficient in NPA. Low enzyme activity is indicative of the disease.
• Genetic testing can identify mutations in the SMPD1 gene, which encodes acid
sphingomyelinase. Molecular analysis confirms the diagnosis and may also be
used for carrier screening in families.

2. Niemann-Pick Type B (NPB):

• Enzyme assays may reveal reduced but detectable acid sphingomyelinase
activity compared to NPA.
• Genetic testing for mutations in the SMPD1 gene confirms the diagnosis.
Molecular analysis aids in distinguishing NPB from NPA and other types of
Niemann-Pick disease.
3. Niemann-Pick Type C (NPC):
• Abnormal lipid profiles, including elevated levels of cholesterol and
sphingomyelin in blood or tissue samples.
• Genetic testing can identify mutations in the NPC1 or NPC2 genes.
Sequencing these genes helps confirm the diagnosis and may provide
insight into disease severity and prognosis. Additionally, molecular
analysis can be used for carrier screening and prenatal testing in at-
risk families.
TREATMENT:
• No effective treatment for Type A.
• Bone marrow transplantation for Type B
• A new treatment Miglustat (a glucosylceramide synthase inhibitor)
has been approved for Type C.
• Individuals with Types C and D are frequently placed on a healthy,
low- cholesterol diet and cholesterol lowering drugs.
• Supportive care through nutrition, medication, physical therapy,
occupational therapy and being followed by specialists can help
relieve many symptoms, e.g. pain and seizures.
REFERENCE:
• https://www.ncbi.nlm.nih.gov/books/NBK556129/
• Thurm A, Chlebowski C, Joseph L, Farmer C, Adedipe D, Weiss M, Wiggs E, Farhat N,
Bianconi S, Berry-Kravis E, Porter FD. Neurodevelopmental Characterization of Young
Children Diagnosed with Niemann-Pick Disease, Type C1. J Dev Behav Pediatr. 2020
Jun/Jul;41(5):388-396. [PubMed]
• Eskes ECB, Sjouke B, Vaz FM, Goorden SMI, van Kuilenburg ABP, Aerts JMFG, Hollak
CEM. Biochemical and imaging parameters in acid sphingomyelinase deficiency:
Potential utility as biomarkers. Mol. Genet. Metab. 2020 May; 130(1):16-26.
[PubMed]
• Bianconi SE, Hammond DI, Farhat NY, Dang Do A, Jenkins K, Cougnoux A, Martin K,
Porter FD. Evaluation of age of death in Niemann-Pick disease, type C: Utility of
disease support group websites to understand natural history. Mol. Genet. Metab.
2019 Apr;126(4):466-469. [PMC free article] [PubMed]
THANK YOU….