lipid storage diseases

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

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

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

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

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

8. Types of lipid storage Types of lipid storage
diseasesdiseases
Niemann pick diseaseNiemann pick disease
Fabry diseaseFabry disease
Farbers diseaseFarbers disease
GangliosidosisGangliosidosis
Krabbe diseaseKrabbe disease
Metachromatic leukodystrophyMetachromatic leukodystrophy
Wolmans diseaseWolmans disease

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

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

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

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

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

15. Type AType A
Infants are normal at birth but at age of six Infants are normal at birth but at age of six
years develop:years develop:
SplenomegallySplenomegally
HepatomegallyHepatomegally
Swollen lymph nodesSwollen lymph nodes
Profound brain damage Profound brain damage
(atraxia,spasticity,slurred speech,loss of muscle (atraxia,spasticity,slurred speech,loss of muscle
tone )tone )
AnemiaAnemia

Susceptible to recurrent infectionsSusceptible to recurrent infections..

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

17. FABRY DISEASEFABRY DISEASE
The only X-linked lipid storage disease.The only X-linked lipid storage disease.
Predominantly affecting males.Predominantly affecting males.
CauseCause
Deficiency of enzyme alpha galactosidase.Deficiency of enzyme alpha galactosidase.
Resulting in accumulation of globosides in nervous Resulting in accumulation of globosides in nervous
tissue,eyes,kidneysand cardiovascular system.tissue,eyes,kidneysand cardiovascular system.
Clinical featuresClinical features
Burning pain in arms and legsBurning pain in arms and legs
CardiomegallyCardiomegally
FeverFever
Renal impairmentRenal impairment

18. Angiokeratomas (small,non cancerous, reddish Angiokeratomas (small,non cancerous, reddish
purple elevated spots on skin ) on lower part of purple elevated spots on skin ) on lower part of
trunktrunk..
TreatmentTreatment
 Enzyme replacement therapyEnzyme replacement therapy
Phenytoin or carbamazepine for painPhenytoin or carbamazepine for pain
Dialysis or renal transplant.Dialysis or renal transplant.

19. AngiokeratomasAngiokeratomas

20. Farber’s diseaseFarber’s disease
CauseCause
Deficiency of the enzyme called ceramidase.Deficiency of the enzyme called ceramidase.
Resulting in accumulation of ceramide in joints , tissues Resulting in accumulation of ceramide in joints , tissues
and central nervous system.and central nervous system.
Clinical featuresClinical features
DyspneaDyspnea
DysphagiaDysphagia
VomitingVomiting
ArthritisArthritis
HorsenessHorseness
XenthemasXenthemas
Joint contracturesJoint contractures

21. TreatmentTreatment
no specific treatment for Farber’s disease. no specific treatment for Farber’s disease.
Most children with the disease die by age Most children with the disease die by age
2.2.

22. Krabbé diseaseKrabbé disease
CauseCause
deficiency of the enzyme beta galactactosidase.deficiency of the enzyme beta galactactosidase.
Resulting in accumulation of galactocerebrosides in Resulting in accumulation of galactocerebrosides in
white matter of CNS and peripheral nerves.white matter of CNS and peripheral nerves.
Clinical featuresClinical features
Onset usually before age 6 monthsOnset usually before age 6 months
HypertoniaHypertonia
SeizuresSeizures
SpasticitySpasticity
IrritabilityIrritability
Optic atrophy and blindness Optic atrophy and blindness

23. DiagnosisDiagnosis
Characteristic grouping of cells into globoid Characteristic grouping of cells into globoid
bodies in white matter of brain.bodies in white matter of brain.
Demyelination of nerves and degeneration Demyelination of nerves and degeneration
and destruction of brain cells.and destruction of brain cells.
TreatmentTreatment
No specific treatmentNo specific treatment
Bone marrow tranasplantation helpful in Bone marrow tranasplantation helpful in
some patients.some patients.

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

25. TteatmentTteatment

Treatment is symptomatic and supportiveTreatment is symptomatic and supportive..
Bone marrow transplantation may delay Bone marrow transplantation may delay
progression of the disease in some casses.progression of the disease in some casses.

26. GangliosidosisGangliosidosis
Two groupsTwo groups
11. . GM 1 Gangliosidosis5GM 1 Gangliosidosis5
CauseCause
Due to deficiency of enzyme beta galactosidaseDue to deficiency of enzyme beta galactosidase
Resulting in abnormal storage of acidic lipid Resulting in abnormal storage of acidic lipid
materials particularly in nerve cells of central materials particularly in nerve cells of central
and periphel nervous system.and periphel nervous system.

27. TypesTypes
a) a) InfantileInfantile
NeurodegerationNeurodegeration
SeizuresSeizures
HepatosplenomegallyHepatosplenomegally
Coarsning of fascial featuresCoarsning of fascial features
Skeletal irregularitesSkeletal irregularites
Distended abdomenDistended abdomen
DeafnessDeafness
BlindnessBlindness

28. Adult typeAdult type
AtrophyAtrophy
DystoniaDystonia
Corneal cloudingCorneal clouding

Angiokeratomas on lower part of trunkAngiokeratomas on lower part of trunk..

29. GM 2 GangliosidosisGM 2 Gangliosidosis
CauseCause
Due to deficiency of enzyme beta hexosaminidase.Due to deficiency of enzyme beta hexosaminidase.
 TypesTypes

1. 1. Tay-Sachs diseaseTay-Sachs disease
CauseCause
Due to deficiency of enzyme beta hexosaminidase A.Due to deficiency of enzyme beta hexosaminidase A.
Resulting in accumulation of gangliosides in nerve cells.Resulting in accumulation of gangliosides in nerve cells.
Clinical featuresClinical features
Initially normal Initially normal
Sign and symptoms begin at age of six monthsSign and symptoms begin at age of six months

30. Rapid and progressive neurodegenerationRapid and progressive neurodegeneration
Cherry red spots in retinasCherry red spots in retinas
Dementia Dementia
DeafnessDeafness
BlindnessBlindness
SeizuresSeizures
TreatmentTreatment
No specific treatmentNo specific treatment
Symptomatic and supportiveSymptomatic and supportive
Anticonvulsants for seizuressAnticonvulsants for seizuress

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

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

33. ReferencesReferences
Lehninger,principles of biochemistry.Lehninger,principles of biochemistry.
Stryer,biochemistry.sStryer,biochemistry.s
Lppincott’s,biochemistry.Lppincott’s,biochemistry.
Tietz,clinicil chemistry.Tietz,clinicil chemistry.
CMDT by Lawrence.CMDT by Lawrence.
Online resourcesOnline resources
 http://www.ninds.nih.govhttp://www.ninds.nih.gov
 http://emedicine.medscape.comhttp://emedicine.medscape.com
 http://www.sharecare.comhttp://www.sharecare.com
 http://www.britannica.comhttp://www.britannica.com