Niemann - pick disease

1. Niemann- pick disease

2. What Is It? • Niemann-Pick disease is an inherited condition which involves lipid metabolism, which is the breakdown, transport, and use of fats and cholesterol in the body. People with this condition, abnormal lipid metabolism causes harmful amounts of lipids to accumulate in the spleen, liver, lungs, bone marrow, and brain.

3. Recessive/Dominant • -Niemann-Pick disease is an autosomal recessive cholesterol-processing disorder. • -This condition is inherited in an autosomal recessive pattern. Both copies of the gene in each cells has mutations. The parents with an autosomal recessive condition each carry one copy of the mutated gene, but they usually do not show the signs and symptoms of the condition

4. Chromosome affected • -The NPC1 gene is located on chromosome 18 and is usually seen in two copies in each cell of the body. • -The NPC2 gene is located on chromosome 14

5. Genetic Mutations • -1997 medical researchers identified the NPC1 gene. • -Alternations or mutations in this gene cause about 95 percent of cases of NP-C disease • -Mutations in the NPC1, NPC2 and SMPD1 genes causes the Niemann-Pick disease. • -Niemann-Pick disease type A and B is cause by Mutations in the SMPD1 gene. • -This gene provides information for producing acid sphingomyelinase which is an enzyme. This enzyme is located in the lyosomes, where it processes lipids such as sphingomyelin. • - Mutations in this gene may lead to a deficiency of acid sphingomyelinase and the gathering of the sphingomyelin, cholesterol, and other kinds of lipid within the cell tissues of the infected individual.

6. Genetic Mutations • -Mutations in there NPC1 or the Npc2 gene causes type c of the Niemann-Pick disease. • -The NPC1 gene provides information on generating a protein that involves alternations of cholesterol and lipids within cells. • -A glitch of this protein may lead to uncommon storage of lipids within cells • -The NPC2 gene provides information to generate protein that binds and transport cholesterol • -A deficiency of this protein leads to uncommon accumulation of lipids and cholesterol in the cell

7. Symptoms • As you all know, there are five different cases of Niemann- pick disease. Each case has different symptoms associated with them. • Type A usually begins from birth. • Abdominal (belly area) swelling within 3 - 6 months • Cherry red spot in the eye • Feeding difficulties • Loss of early motor skills (gets worse over time) • Type B symptoms usually occur during late childhood. There is almost no brain and nervous system involvement, such as loss of the ability to move your muscles. Some patients may have respiratory infections.

8. More Symptoms • Type C and type D are quite similar to each other. Usually affects children in school and it can occur during any phase. • Difficulty moving limbs • Enlarged spleen • Enlarged liver • Learning difficulties • Seizures • Slurred, irregular speech • Sudden loss of muscle tone which may lead to falls • Involuntary shaking of the body or limbs. • Trouble moving the eyes up and down • Clumsiness, walking problems. • Type E occurs in adults. Symptoms include swelling of the spleen and brain as well as the nervous system. This type of disease is a rare case and no treatment has been discovered as yet.

9. Inheritance • Niemann-pick disease is inherited in an autosomal recessive pattern, which means the trait is transmitted to both genders and both of them can carry the gene. Both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

11. Tests • Type A and B are diagnosed by measuring the level of activity of an enzyme called acid sphingomylinase. This test can be carried out using a blood or bone marrow sample. Such testing can tell who has the disease, but does not reveal who may be carriers. In order to determine if carriers have type A or type B of the disease, DNA tests can be done. • To determine if the carriers have type C or type D, a skin biopsy is used. This is the removal for diagnostic study of a piece of tissue from a living body. Laboratory scientists closely examine and watch how the skin cells grow, They also keep track of how they move and store cholesterol. DNA tests may also be done to look for the two genes that cause Niemann-Pick disease Type C.

12. Other Tests • Bone marrow aspiration • Liver biopsy (usually not necessary) • Slit lamb eye-exam • Sphingomyelinase assays

13. Treatments • There is no treatment for Type A at this time. • Bone marrow transplantation has been performed on a few patients with Type B. This method has been successful in treating the patient. Researchers still continue to find more treatments, including enzyme replacement therapy and gene therapy. • There is no specific treatment for Type D yet. There is a new treatment for type C which is called miglustat which is recently a new treatment that has been approved.

15. More Treatments • Something that researchers have mentioned to help overcome this disease is to maintain a low-cholesterol diet, Upon doing this, it has been found out that cholesterol-lowering drugs does not show that these methods stop the disease from getting worse or change how cells break down cholesterol. However, there are medicines to treat many symptoms, such as seizures.

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