1. LIPID STORAGE DISEASES
Presented by,
DR. AHMAD JAN
Student M. Phil
Chemical Pathology
FPGMI Lahore

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;-
• Important constituent of the cell membranes.
• Helps in the absorption of fat soluble
vitamins.
• Maintains membrane fluidity.
• Acts as a thermal insulator and cellular
metabolic regulator.
• Hormone synthesis.
• 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