This presentation is about Niemann Pick Type A,B and C disease with case reports.

1. PRESENTATION ON NIEMANN-
PICK BY-
Preshika
Yashmeet
Sudiksha
Shashi

2. CASE REPORT 1
A 19 months old child from Rajasthan came with a history of apparently normal growth and development upto 5 months of
age. There after the child developed gradual distension of abdomen, unable to hold neck and unable to recognized her parents.
On examination :
• Liver and spleen were enlarged by 10 and 12 cm respectively.
• Blood examination showed reduced haemoglobin.
• All the deep reflexes were diminished and there was hypotonia in all four limbs.
• Bone marrow examination showed infiltration of foamy cells in macrophages.
 Fundus examination revealed cherry red spot in the macula of both eyes. Hence, this characteristic is seen in many types
of storage diseases so this cannot simply confirm the presence of Niemann-Pick.
Expected Diseases according to above information- 1) Gaucher Disease
2) Tay Sachs Disease
3) Hurler’s syndrome
4)Niemann-pick disease
 Further Enzymatic and gene studies revealed the presence of Niemann-Pick Type A disease. In gene study, gene
expression was studied.

3. CASE REPORT 2
An Afghan girl was growing normally till 1 year of age. Later on, hepatomegaly with
developmental delay was observed. Parents also noticed unexplained frequent falls without any
sign of seizure.
She was the 5th sibling with one elder sister dying of respiratory failure and hepatosplenomegaly
at the age of 5 years. Two elder brothers and one sister were normally growing till that date.
On examination: At the age of 4 yrs, she had
• neurological regression
• hypotonia
• facial dyskinesia
• Bone-marrow examination revealed presence of storage cells
Expected Diseases related to these symptoms- 1) Gaucher Disease
2) Niemann-Pick Disease

4. •This was found to be normal making it unlikely for Gaucher or NPD type A or B.
• Further study was carried out on skin fibroblast for demonstration of unesterified cholesterol
accumulation in cultured cells by filipin staining method, which is the characteristic of NPD type C.
LYSOSOMAL ENZYME CLINICAL VALUE NORMAL VALUE
β-Glucosidase 8.84 nmol/hr/mg protein 8.21±3.11 nmol/hr/mg protein
Acid-sphingomyelinase 1.16 nmol/hr/mg protein 1.55±0.78 nmol/hr/mg protein
• Lysosomal study was carried out-

6. What is Niemann pick disease ?
 It is the group of inherited severe metabolic disorders that allow a certain kind of fat
to accumulate in cells.
 It is neurodegenerative disorder because of the cells inabilty to metabolize
cholesterol.
 It is an autosomal recessive disorder.
 This involves dysfunction metabolism of sphingolipids and sphingomyelin in
lysosomes that results in accumulation of these in lysosomes.
 It is a type of lysosomal storage disease.
 It affects 1 out of 150,000 births hence it is rare.

7. INHERITANCE

8. Biochemical pathway

9. TYPES
Niemann type A or B
• It is caused by mutation in gene SMPD1.
• SMPD1 gene carries instructions for cells to
produce sphingomyelinase which processes
lipids.
• In these, a lysosomal enzyme acid
sphingomyelinase is deficient, which catalyse
the conversion of sphingomyelin to ceramide.
Niemann type C1 or C2
• It is caused by mutation in a gene NPC1 and
NPC2.
 NPC1 gene produces a protein involve in the
movement of cholestrol and lipids within cells.
 NPC2 gene produces protein that binds and
transport cholestrol.
• In these,a lysosomal membrane protein is
deficient involved in movement of cholestrol in
and out of the cell.

10. SIGNS AND SYMPTOMS
Symptoms are related to the organs in which sphingomyelin accumulates:
• Enlargement of liver (hepatomegaly) may cause reduced appetite, abdomen distension and pain.
• Enlargement of spleen(spleenomegaly) may also cause low levels of platelets in the
blood(thrombocytopenia).
• Accumulation of sphingomyelin in CNS results in slurring of speech , difficulty in swallowing
(dysphagia), abnormal posturing of limbs trunk and face.
• Bones may also affected : Enlarged bone marrow cavities
More widespread disease involving cerebral cortex causes gradual loss of intellectual abilities
causing dementia and seizures.

11. DIAGNOSIS
• It can be made on DNA analysis if the mutations in the affected child are known.
• Pre natal testing :-
Available for type C
Cells can be grown from samples taken at around 11 weeks of pregnancy and then
observed.

12. TREATMENT
 No specific treatment is known but symptoms can be treated.
 In adult patients with type B, physicians try to keep cholestrol level down to normal level.
 Used statins to monitor liver function.
 If spleen is enlarged and platelets level are low , acute episodes of bleeding may require transfusion of
blood products.
 Organ transplant has been attempted with limited success.
 Gene therapies, enzyme therapies and bone marrow transplantation.
 A drug Zavesca Migulstat has been approved in European union for treatment of neurological
manifestations of Niemann pick disease type C.

13. THANK YOU