Lipid storage diseases are a group of inherited metabolic disorders where lipids accumulate abnormally in cells and tissues due to deficiencies in lipid-metabolizing enzymes. This excess lipid storage can damage organs like the brain, liver, and spleen over time. The most common type is Gaucher disease, caused by a glucocerebrosidase enzyme deficiency leading to glucocerebroside accumulation in the spleen, liver, and bone marrow. Other types include Niemann-Pick disease, Fabry disease, and Tay-Sachs disease. While some forms can be treated through enzyme replacement therapy, most have no cure and treatment focuses on managing symptoms.

1. LIPID STORAGE DISEASES

2. Lipids
Lipids are fat-like substances that are important parts of the
membranes found within and between each cell and in the
myelin sheath that coats and protects the nerves. Lipids
include oils, fatty acids, waxes, steroids (such as cholesterol
and estrogen), and other related compounds.

4. Why lipids are important-
Lipids are important to the body because;-
1) Important constituent of the cell membranes.
2) Helps in the absorption of fat soluble
vitamins.
3) Maintains membrane fluidity.
4) Acts as a thermal insulator and cellular
metabolic regulator.
5) Hormone synthesis.
6) Organ padding.
•

5. Lipid storage diseases
 Lipid storage diseases, or lipidoses, are a group of inherited
metabolic disorders in which harmful amounts of fatty materials
called lipids accumulate in some of the body's cells and tissues.
People with these disorders either do not produce enough of one
of the enzymes needed to metabolize lipids, or they produce
enzymes that do not work properly. Over time, this excessive
storage of fats can cause permanent cellular and tissue damage,
particularly in the brain, peripheral nervous system, liver, spleen,
and bone marrow.

6. Inheritance
Lipid storage diseases can be inherited two ways
1. Autosomal recessive inheritance occurs when both parents
carry and pass on a copy of the faulty but none of the parents
show symptoms of disease.
2. X-linked recessive (or sex linked) inheritance occurs when
the mother carries the affected gene on the X chromosome that
determines the child’s gender and passes it to her son.

7. Pathophysiology
 Because glycosphingolipids are essential components of all cell
membranes, inability to degrade these substances and their subsequent
accumulation results in physiologic and morphologic alterations of
specific tissues and organs that lead to characteristic clinical
manifestations. In particular, progressive lysosomal accumulation of
glycosphingolipids in the central nervous system can lead to a
neurodegenerative course; whereas, storage in visceral cells can lead to
organomegaly, skeletal abnormalities, bone marrow dysfunction,
pulmonary infiltration, and other manifestations.

8. Types of lipid storage
diseases
Niemann pick disease
Fabry disease
Farbers disease
Gangliosidosis
Krabbe disease
Metachromatic leukodystrophy
Wolmans disease

10. Gaucher disease
 most common of the lipid storage diseases
Cause
 caused by a deficiency of the enzyme glucocerebrosidase.
 Resulting in accumulation of glucocereboside in spleen ,liver,
kidneys,lungs,brain and bone marrow.
CLINICAL FEATURES
Type 1 (non neuropathic form ) May be
asymptomatic.
 Begin early in life
 Bruise easily
 Fatigue

11. Hepatomegally
Spleenomegally
Brain not affected
Type 2 (acute infantile neuropathic )
Begins within three months of birth.
Poor ability to suck and swallow.
Abnormal eye movements.
Extensive and progressive brain damage.
Spasticity, Seizures and Limb rigidity.
Hepatomegally and Splenomegally.

12. Type 3 (chronic neuropathic )
Can begin at any time in child hood or even inadult hood but
milder neurologic symptoms as compared to type two.
Respiratory problems.
Anemia.
Skeletal problems.
Treatment
For type 1 and most type 3 patients, enzyme replacement
treatment given

13. intravenously every two weeks can dramatically decrease liver
and spleen size, reduce skeletal abnormalities and other
manifestations.
bone marrow transplantation cures the non-neurological
manifestations.
Blood transfusion for anemia.
Splenectomy (rarely )
No effective treatment for brain damage.
Prognosis
Type 1: may live well into adulthood.
Type 2: usuallyo teen age die before age two.
Type 3: live to teen age.

14. Niemann-Pick disease
Cause
Niemann-Pick types A and B result from accumulation of the
fatty substance called sphingomyelin, due to deficiency of an
enzyme called sphingomyelinase.
 Resulting in accumulation of sphingomyelin in liver,spleen, bone
marrow,lungs and in some patients in brain.

15. Type A
Infants are normal at birth but at age of six years develop:
Splenomegally
Hepatomegally
Swollen lymph nodes
Profound brain damage (atraxia,spasticity,slurred
speech,loss of muscle tone )
Anemia
Susceptible to recurrent infections.

16. Type B
enlargement of the liver and spleen characteristically occurs
in the pre-teen years.
Most patients also develop ataxia, peripheral neuropathy,
and pulmonary difficulties progress with age.
Brain is generally not affected.
Treatment
There is currently no cure for Niemann-Pick disease.
Treatment is supportive.

17. FABRY DISEASE
 The only X-linked lipid storage disease.
 Predominantly affecting males.
Cause
 Deficiency of enzyme alpha galactosidase.
 Resulting in accumulation of globosides in nervous
tissue,eyes,kidneysand cardiovascular system.
Clinical features
 Burning pain in arms and legs
 Cardiomegally
 Fever
 Renal impairment

18. Angiokeratomas (small,non cancerous, reddish purple
elevated spots on skin ) on lower part of trunk.
Treatment
 Enzyme replacement therapy
Phenytoin or carbamazepine for pain
Dialysis or renal transplant.

19. Angiokeratomas

20. Farber’s disease
Cause
 Deficiency of the enzyme called ceramidase.
 Resulting in accumulation of ceramide in joints , tissues and central
nervous system.
Clinical features
 Dyspnea
 Dysphagia
 Vomiting
 Arthritis
 Horseness
 Xenthemas
 Joint contractures

21. Treatment
no specific treatment for Farber’s disease.
Most children with the disease die by age 2.

22. Krabbé disease
Cause
 deficiency of the enzyme beta galactactosidase.
 Resulting in accumulation of galactocerebrosides in white matter of
CNS and peripheral nerves.
Clinical features
 Onset usually before age 6 months
 Hypertonia
 Seizures
 Spasticity
 Irritability
 Optic atrophy and blindness

23. Diagnosis
Characteristic grouping of cells into globoid bodies in white matter
of brain.
Demyelination of nerves and degeneration and destruction of brain
cells.
Treatment
No specific treatment
Bone marrow tranasplantation helpful in some patients.

24. Metachromatic
leukodystrophy
Cause
 Due to deficiency of enzyme arylsulfatase A.
 Resulting in accumulation of sulfatides in CNS, peripheral nerves and
kidneys.
Clinical features
 Normal at birth
 Develop difficulty in walking and tendency to fall followed by
intermittent pain in arms and legs.
 Progressive loss of vision leading to blindness.
 Developmental delays.
 Dementia.

25. Tteatment
Treatment is symptomatic and supportive.
Bone marrow transplantation may delay progression of the
disease in some casses.

26. Gangliosidosis
Two groups
1. GM 1 Gangliosidosis5
Cause
Due to deficiency of enzyme beta galactosidase
Resulting in abnormal storage of acidic lipid materials
particularly in nerve cells of central and periphel nervous
system.

27. Types
a) Infantile
Neurodegeration
Seizures
Hepatosplenomegally
Coarsning of fascial features
Skeletal irregularites
Distended abdomen
Deafness
Blindness

28. Adult type
Atrophy
Dystonia
Corneal clouding
Angiokeratomas on lower part of trunk.

29. GM 2 Gangliosidosis
Cause
 Due to deficiency of enzyme beta hexosaminidase.
 Types
1. Tay-Sachs disease
Cause
 Due to deficiency of enzyme beta hexosaminidase A.
 Resulting in accumulation of gangliosides in nerve cells.
Clinical features
 Initially normal
 Sign and symptoms begin at age of six months

30. Rapid and progressive neurodegeneration
Cherry red spots in retinas
Dementia
Deafness
Blindness
Seizures
Treatment
No specific treatment
Symptomatic and supportive
Anticonvulsants for seizuress

31. 2. Sandhoff disease
Cause
Due to deficiency of enzyme beta hexosaminidase A and B.
Resulting in accumulation of gangliosides and globosides in
nerve cells.
Clinical features
Same as Tay-sachs disease plus visceral involvement i.e
hepatosplenomegally.
Treatment
Same as Tay-sachs disease.

32. Diagnosis
Diagnosis is made through clinical examination, biopsy, genetic
testing, molecular analysis of cells or tissues, and enzyme assays
(testing a variety of cells or body fluids for enzyme deficiency).
In some forms of the disorder, a urine analysis can identify the
presence of stored material.

33. References
Lehninger,principles of biochemistry.
Stryer,biochemistry.s
Lppincott’s,biochemistry.
Tietz,clinicil chemistry.
CMDT by Lawrence.
Online resources
 http://www.ninds.nih.gov
 http://emedicine.medscape.com
 http://www.sharecare.com
 http://www.britannica.com