lipid storage disease and dyslipidemia

1. M.Manjuladevi
II M.Sc Home science

3.  Any of a group of relatively rare hereditary
disorders of fat metabolism, characterized
by the accumulation of distinctive types of
lipids;
 Gangliosides,
 Cerebrosides, or
 Sphingomyelins, in various body structures.
 Each types of lipid accumulates as a result of
a defect in one of the several organic
catalysis or enzymes that normally
metabolize it inside the cell.

4.  Biomedical defect –
 This is an inborn error of metabolism due to
failure of degradation of gangliosides.
 The enzyme hexosainidase A is deficient.
 Composed of an alpha and beta subunits.
 Mutation in alpha subunit, 15q23

5.  Tay- Sachs disease is classified in various
forms based on the time of onset of
neurological symptoms

6.  Infantile TSD
 Birth: normal but develop
 Loss of motor
 Increased startle reaction
 Macular pallor and retinal cherry red spot
 5-6 months
 Decreased eye contact
 Hyperausis
 Progressive development of idiocy and blindness
are diagnostic of the disease and they are due to
wide spread injury to ganglion cells, in brain and
retina.

7.  Juvenile TSD
 Extremely rare,
 Presents itself in children between 2-10 years
develop cognitive,
 Motor, speech difficulties (dysarthria),
 Swallowing difficulties (dysphagia),
 Unsteadiness of gait (ataxia) and spasticity,
 Patients with juvenile TSD usually die between5-
15years.

8.  Adult/ late onset TSD
 Rare form of the disorder
 Occurs in patients in their 20s and early 30s
 It is characterized by
 Unsteadiness of gait and
 Progressive neurological deterioration
 Symptoms of LOTS, Include
 Speech and swallowing difficulties
 Unsteadiness of gait,
 Spasticity, cognitive decline,
 psychiatric illness

9.  Is usually suspected in an infant with neurologic
features and a cherry-red spot
 Enzymatic Assays- definitive diagnosis is by
determination of the level of β-hexosaminidase A in
isolated blood leukocytes.
 Fine needle Aspiration Cytology of brain tissue- Can
show the degree of neuronal degeneration. FNAC has
a great potential for diagnosis and follow-up of Tay-
Sachs disease.
 Prenatal screening- Future at-risk pregnancies for
both disorders can be monitored by prenatal
diagnosis by amniocentesis or chronic villas
sampling.
 Carrier screening- Identification of carriers within
families is also possible by β-hexoaminidase A and B
determination.

10.  No Cure for this disease.
 Symptomatic treatment is given.
 Enzyme replacement therapy and Gene
therapy are under trial.

11.  This disease is a multisystem lipidosis
characterized by hematological changes,
organomegaly and skeletal involvement,
manifested in the form of bone pains and
multiple fractures.
 It is the most common genetic disorder
among Ashkenazi Jews.
 It is the lysosomal storage disease.

12.  Results from deficient activity of Lysosomal
Hydrolase,β-Glucocerebrosidase.
 Enzyme defect results in accumulation of
undegrated glycolipid in the form of Glucosyl
ceramide in the cells of reticuloendothelial
system.

13.  There are three clinical subtypes
 Type-1 (from early childhood-adulthood)
 Easy bruising due to thrombocytopenia, chronic
fatigue due to anemia, hepatomegaly.
 Progressive enlargement of spleen.
 Clinical bone involvement in the form of bone
pains, or pathological fractures.

14.  Type -2
 Less common.
 Characterized by neurodegeneration, extreme
visceral involvement.
 Death within 2 years of life.
 Type-3
 Is intermediate in presentation to type 1 and 2.
 Neurological involvement is there but occurs
later in life with decreased severity as compared
to Type 2.

15.  Enzyme activity testing:
 A finding of less than 15% of mean normal
activity is diagnostic.
 Genotype testing:
 Molecular diagnostic can be helpful.
 Especially in Ashkenzi patients.
 Complete blood count:
 To assess the degree of cytopenia.
 Liver function enzyme testing:
 The presence of jaundice or impaired
hepatocellular synthetic function.

16.  Ultrasonography
 Hip MRI may be useful in revealing early
avascular nephrosis
 Skeletal ratiology
 Liver biopsy

18.  Enzyme replacement therapy (ERT) by
recombinant β-Glucocerebrosidase is
currently done.
 Surgical care:
 Partial and total splenectomy was once
advocated the treatment of patients with
Gaucher disease.
 Bone marrow transplant is also helpful.
 Gene replacement is the permeanent cure.

19.  Occurs due to impaired degradation of
shingomyelins.
 There is deficiency of sphingomyelinase
enzyme.
 Due to non degradation, there is
accumulation of shingomyelin in liver,
spleen, bone marrow and brain.

20.  Is a congenital disease.
 Autosomal recessive in native.
 There are 2 type: A and B.
 Type A: more common present in 1/40000
population.
 Type B: present in 1/80000 population.
 More common in Jewish population

21.  Type A Niemann Pick disease: there is
progressive mental retardation,
hepatosplenomegaly because of progressive
accumulation of sphingomyelin.
 Children die within 2 years of life.
 Type B: there is no involvement of brain but
sphingomyelin is present in excessive amount
in liver, spleen, and bone marrow.
 Death occurs within 20 years of life.
 Treatment :only symptomatic treatment is
given.

22. Niemann-pick disease (type A and B)
Autosomal recessive disease
Inability to degrade sphingomyelin
The deficient enzyme is
sphingomyelinase- a type of
phospholipase C

23.  Type A- less than 1%normal activity
 Lipid deposit in liver and spleen -> increase
size of liver and spleen, Neuron –
degeneration
 Type B-5% or more normal activity
 Little to no damage to neural tissue, but
lungs, spleen, liver and bone marrow are
affected
 Mostly commonly affect jaws

24.  Krebbe’s disease (globoid cell
leukodystrophy) is a degenerative disorder
that affects the nervous system
 It’s heredity autosomal recessive disease
 It affects the myelin sheath of the nervous
system
 Knud Harlesden Krebbe

25.  Mutation in the GALC gene, causing
deficiency of enzyme galactosylceramidase.
 This effects the growth and maintenance of
myelin, which cause severe degeneration of
motor skills
 Krabbe disease is a leukodystrophy

26.  There is no cure at present time
 Treatment is centered around the
tolerated of systems related to Krebbe
Disease

29.  Disorder of lipids & lipoprotein metabolism
 A common form of Dyslipidemia is
characterized by the three lipid
abnormalities:
 Elevated triglyceridase
 Elevated LDL and
 Reduced HDL cholestrol
 Important modifiable Risk Factor for CAD
 Cholesterol is a fatty substance manufactured in
the liver and is carried throughout the body in
the bloodstream.

30.  High cholesterol does
not cause any
symptoms.
 Too much cholesterol
may lead to a buildup
of plaque inside the
arteries.
 This is known as
atherosclerosis, a
condition that causes
narrowing of the
space available for
blood flow

31.  Primary and secondary
 Primary –familial dyslipidemia
 Secondary –acquired

34.  Dyslipidemia usually doesn’t cause
symptoms, it can lead to symptomatic
vascular disease, which include CORONARY
ARTERY DISEASE(CAD)
 These with high concentration of LDL

35.  Clinical features
1. Premature arcus senilisop – a white or gray
opaque ring in the corneal margin
2. Tendon xanthomata – these are hard, non-
tender nodular enlargement of tendons.
They are most commonly found on the
knuckled and the Achillies tendons.
3. Xanthelamas - fatty deposits in eyelids

36.  About 50% of U.S. adults have an elevated total
cholesterol level
 Majority of patients with atherosclerosis have
some form of dyslipidemia
 70-80% of individuals with dyslipidemia do not
meet LDL cholesterol targets despite lipid
therapy

38.  Increasing age
 Gender (at younger aged, males are most at risk.
Premenopausal women are relatively protected; after
menopause the risk in women increase and eventually
exceeds the risk in males
 Family history
 Genetic abnormalities (yet fully not explained)
 Hyperlipidemia
 Hypertension
 Cigeratte smoking (smoking potentiates the other risk
factors)
 C- reaction protein level(increased in atherosclerosis)

39. 1. Endothelial damage -(smoking,
hypertension, elevated blood cholestrol)
2. Fatty streak formation in the vessel wall
3. These accumulations contain both living,
active WBCs (producing inflammation) and
remnants of dead cells, including cholestrol
and triglycerides
4. Calcification of the lesion
5. Reduction in the arterial wall diameter and
elasticity

40.  Eat more fiber
 Know your fats
 Smart protein
 Low-carb diet

41.  There's growing evidence that
low-carb diets may be better
than low-fat diets for
improving cholesterol levels.
 In a two-year study funded by
the National Institutes of
Health, people who followed a
low-carb plan had significantly
better HDL (good cholesterol)
levels than those who followed
a low-fat plan.

42.  Lose weight
 Quit smoking
 Exercise

43.  If you're overweight, talk to
your doctor about beginning
a weight loss program.
 Losing weight can help you
reduce your levels of
triglycerides, LDL, and total
cholesterol.
 Good cholesterol level tends
to go up 1 point for every 6
pounds you lose.

44.  Tobacco use is one of
the most important risk
factors for CHD
 It is the most
preventable cause of
death in the US
 440,000 deaths each
year are attributable to
tobacco use
 When you stop smoking,
your good cholesterol is
likely to improve

45.  If you're healthy but not
very active, starting an
aerobic exercise program
could increase your good
cholesterol by 5% in the
first two months.
 Regular exercise also
lowers bad cholesterol.
Choose an activity that
boosts your heart rate,
such as running,
swimming, or walking
briskly
 Aim for at least 30
minutes on most days of
the week. It doesn't have
to be 30 continuous
minutes; two 15-minute
walks works just as well.

46.  Statins
 Non-Statins
Cholesterol Absorption Inhibitor
(Ezetimibe)
Nicotinic Acid (Niacin)
Bile Acid Sequestrants
Fibric Acid Derivatives
Omega-3 Fatty Acids

47.  In the treatment of dyslipidemia:
Statins are the most effective and safe first
line of treatment.
Non-statins, which include cholesterol
absorption inhibitors, niacin, bile acid
sequestrants, fibrates, and omega-3 fatty
acids, probably help improve the outcomes
of patients with CHD, although strong
evidence remains lacking.
 Triglycerides are now considered as an
independent risk factor for CHD.