2. Introduction to lipids
Lipid storage disorders
Inheritance of lsd
Pathophysiology
Types of lsd
Elaboration on lsd
3. Introduction-lipids
■ Fat like substances – important parts of membranes
■ It includes oils,fatty acids,waxes, steroids and other
related compounds
IMPORTANCE OF LIPIDS
■ Important constituents of cell membranes
■ Helps in absorption of fat soluble vitamins
■ Maintains membrane fluidity
■ Acts as thermal insulator and cellular metabolic
regulators
■ Aids in hormone synthesis
4. LIPID STORAGE DISEASES
■ Lipid storage diseases or lipodosis are a group of inherited
metabolic disorders in which harmful amount of fatty materials
called lipids accumulate in some of the body cells and tissues.
■ People with these order - do not produce enzyme to metabolize
lipid or produce enzymes that do not metabolize properly.
■ Overtime it causes permanent cellular and tissue damage
■ Especially in brain, peripheral nervous system,liver, spleen and
bone marrow.
5. INHERITANCE OF LSD
■ Two means of inheritance - autosomal recessive and X- linked
recessive
AUTOSOMAL RECESSIVE
■ Occurs when both parents carry and pass on copy of faulty but
none of the parents show symptoms
X- LINKED RECESSIVE
■ Inheritance occurs when mother carries affected gene on the X-
chromosome which determines the child’s gender and is passed to
the son
6. PATHOPHYSIOLOGY
■ Glycosphingolipids are essential components of all cell
membranes,inability to degrade these substances and their
accumulation results in physiologic and morphologic alteration of
specific tissues and organs which lead to characteristic clinical
manifestation.
■ In particular,progressive lysosomal accumulation of sphingolipids
in the cns can lead to a neurodegenerative course whereas
storage in visceral cells can lead to organomegaly, skeletal
abnormalities, bone marrow dysfunction, pulmonary infiltrationand
other manifestations.
8. 1.GAUCHER’S DIS
■ Most common type of lsd
CAUSE
■ Deficiency of enz glucocerebrosidase
■ Accumulation of glucocerebroside in spleen, liver, kidneys, lungs,
brain and bone marrow
9. Types and symptoms
Type 1
Non neuropathic
Type2
Acute
neuropathic
Type3
Chronic
neuropathic
Age of onset adults infants juvenile
Incidence 1 in 100000 1 in 100000 live
births
1 in 50000
Clinical
presentation
Hepatosleenomeg
aly
Bone marrow
suppression
Bone
abnormalities and
fractures
Hepatospleenome
galy
Seizure
Dementia
Ocular apraxia
spasticity
Hepatospeenomeg
aly
Seizure
Dementia
Ocular apraxia
spasticity
Enzyme Some activity Very little little
10. Diagnosis
■ Made via positive gaucher cells in a bone marrow aspirate
■ Contains monocytes and monocytoid cells which contain
inclusions which are acid phosphatase positive and resemble the
acid phosphatase positive inclusions in the Gaucher cells.
■ Enzyme beta glucocerebrosidase activity is assayed
12. 2.NIEMANN PICK’S DIS
CAUSE
■ It is of type A and B resulting from accumulation of fatty substance
called
Sphingomyelin ,due to deficiency of an enzyme called
sphingomyelinase.
■ It results in accumulation of sphingomyelin in liver, spleen,
bone marrow, lungs and in brain.
13. Types and symptoms
Type A Type B
Age of onset Infants are normal at birth,
but at age of six, disease
onsets.
Pre teen years
Symptoms Spleenomegaly
Hepatomegaly
Swollen lymph nodes
Ataxia
Spasticity
Slurred speech
Loss of muscle tone
Anaemia
Susceptible to infections
Ataxia
Pheripheral neoropathy
Hepatoaspleenomegaly
Pulmonary difficulty
Brain
15. 3.Fabry’s dis
Cause
■ It is an x-linked disease
■ Caused by deficiency of alpha galactosidase A
■ Causes fat accumulation in the ANS , eyes, kidneys, and
cardiovascular system
■ Onset is usually at childhood
16. Symptoms
■ Burning pain in arms and legs
■ Corneal clouding
■ Stroke or heart attack due to fatty storage in blood vessel walls
■ Cardiac and renal failure
■ Reduced sweating and gi tract motility reduced
■ Angiokeratoma
■ Early death is caused due to cardiac or renal complications
20. KRABBE DIS
CAUSE
■ Caused by def of beta galactosidase
■ Results in accumulation of galactocerebrosides in white matter of
cns and pns
SYMPTOMS
■ Onset is usually before 6months
■ Hypertonia
■ Seizures
■ Spasticity
■ Irritability
■ Optic atrophy and blindness
21. Diagnosis
■ Characterized by grouping of cells into globoid bodies in
whitematter of brain
■ There is also demyelination of nerves and degeneration and
destruction of brain cells
23. 5.Metachromatic leukodystrophy
CAUSE
■ Def enz is arylsulphatase A resulting in accumulation of sulfatides
in CNS and PNS
SYMPTOMS
■ Developed normally at birth
■ Infant develops difficulty in walking and tendency to fall followed by
intermittent pain in arms and legs
■ Other symp include loss of vision leading to blindness and
developmental delays and dementia
24. Treatment
■ It is sympathomatic and supportive
■ Bone marrow transplantation may delay the dis progression
26. 6A.GM1 GANGLIOSIDOSIS
CAUSES
■ Caused due to def of enz beta galactosidase
■ Results in abnormal storage of acidic lipid materials particularly in
nerve cells of cns and pns
TYPES AND SYMPTOMS
■ 2 types based on age of onset
TYPES SYMPTOMS
Infantile Neurodegerative, seizure, hepatospleenomegaly, coarsing
facial feature, skeletal irregularity, deafness and blindness
Adult
type
Atrophy, dystonia, corneal clouding, angiakeratoma
27. 6B.GM2 GANGLIOSIDOSIS
CAUSES
Caused due to def of enz beta hexoaminidase
TYPES
6B1.TAY SACCH’S DIS
CAUSE
■ Due to def of enzbeta hexoaminidase A
■ Resulting in accumulation of gangliosides in nerve cells
28. Symptoms
■ Iniyially patient appears normal with sign and symp beginning at
age of 6 months
■ Clinical features include
■ Rapid and progressive neuro degeneration
■ Cherry red spots in retina
■ Dementia
■ Deafness
■ Blindness
■ Seizure
29. Treatment
■ No specific treatment available
■ Symptomatic and supportive care
■ Anticonvulsants are given for seizures
30. 6B2.Sandhoff dis
CAUSE
■ Due to def of enz beta hexoaminidase A and B
■ Results in accumulation of gangliosides and globosides in nerve
cells
SYMPTOMS
■ Neurodegeneration
■ Red spots in retina
■ Dementia
■ Deafness
■ Blindness
■ Hepatospleenomegaly
■ Seizures
31. Diagnosis
■ Made through clinical examination , biopsy, genetic testing,
molecular testing of cells or tissues and enzyme assays
■ Urine analysis can identify stored material
32. Tabulation of LSD
DISEASE DEFECTIVE
ENZ
MAJOR
STORAGE
COMPOUN
D
SYMPTOMS TREATMEN
T
NIEMANN
PICK DIS
Sphingomyelina
se
Sphingomyelins Hepatomegaly
Sleenomegaly
Mental
retardation
No cure
FARBERS
DIS
Ceramidase Ceramide Painful and
deformed joints
Enzyme
replacement
therapy
Dialysis or
renal transplant
GAUCHER
S DIS
Beta
galactosidase
Glucocerebrosid
es
Hepatomegaly
Spleenomegal
y
Osteoporosis
Mental
retardation
Enzyme
replacement
treatment
33. DISEASE DEFECTIVE
ENZYME
MAJIR
STORAGE
COMPOUN
D
SYMOTOMS TREATMEN
T
KRABBE
DIS
Beta
galactosidase
Glucocerebroside
s
Absence of
myelin formation
Hepatomegaly
Spleenomegaly
Mental
retardation
No specific
treatment
Bone
transplantarion
is helpful
TAY
SACCH’S
DIS
Hexo aminidase
A
Ganglioside GM2 Blindness
Mental
retarrdation
Death with 2-3
years
No specific
treatment
Symtomatic
and supportive
care
Anticonvulsant
for seizure
FABRYS
DIS
Alpha
galactosidase
Ceramide
trihexoside
Renal failue
Skin rash
Pain in lower
extremities
Dialysis renal
replacement
Enz
replacement
