Diseas Lipid Enzyme Primar Symptoms Defining

e Accumulate Deficiency y Characteris

d Affecte tics
d
Organ
Sandh GM2 Hexosaminid Neuron Same neurological
off Ganglioside ase A & B s of symptoms as Tay-
Diseas (beta brain Sachs (clinically
e subunit) and indistinguishable)
(AR) spinal but with visceral
cord involvement as well
Tay- GM2 Hexosaminid Neuron *Infants are normal *Lysosome
Sachs Ganglioside ase A s of at birth and s with
Diseas (alpha brain develop first onion skin/
e subunit) and symptoms at 6 whorlded
(AR) spinal months conformati
cord *muscles for on
(mutations movement weaken
in these =>
genes lose motor skills
mostly such as turning
cause over, sitting, and
problems in crawling
protein *exaggerated
folding) startle reaction to
loud noises
*seizures, vision
and hearing loss,
intellectual
disability, and
paralysis as disease
progresses
*cherry red spots
found on retinal
 exam in almost all
patients
*more common in
Ashkenazi (eastern
and central
European) Jewish,
French-Canadian
communities of
Quebec, the Old
Order Amish
community in
Pennsylvania and
the Cajun
population of
Louisiana.
*Death is usually
by 3 years
Fabry A- Ceramide Heart, *Angiokeratomas (t *Enzyme
Diseas Galactosidas Trihexoside Brain, elangiectasias of replacemen
e e (Also called Kidney skin) that are blue- t therapy is
(XR) globotriaosyl s black to red and do now
ceramide) not blanch they available
increase in size and *Spoke-
(A number as patient wheel
globoside) ages and are most cataract
dense on upper
legs
* "burning" or "hot"
pain in the hands
and feet that may be
triggered by exposure to
extremes of temperature,
stress, emotion, and/or
fatigue.
 * cloudiness of the
front part of the
eye (corneal
opacity)
* Lipid storage may
lead to impaired
blood circulation
and increased risk
of heart attack or
stroke or renal
failure (ischemic
infarction of the
kidney,
heart, and brain)
* Other signs
include decreased
sweating, fever,
and gastrointestinal
difficulties.
*May have ringing
in the ears and
hearing loss.
*A milder form is
more common in
females
Niema Sphingomyel Sphingomye Brain, A: *Affected
nn-Pick inase lin spleen, *Normal until about cells
liver,
Diseas age 1: progressive have a
lungs,
e Type and bone loss of mental foamy,
A&B marrow abilities and vacuolated
movement
*Usually develop appearanc
(hepato)splenomeg edue
aly by age 3 to
(usually deposition
splenomegaly is oflipids.
much more *
prominent than the
hepatomegaly)
*Interstitial lung
damage =>
recurrent infections
*Almost all have a
cherry red spot
*Do not survive
past early
childhood

B:
*Usually present
symptoms by mid
childhood
*Similar symptoms
to A but less severe
*Generally no
CNS
involvement/neur
odegeneration
*Short stature and
slowed
mineralization of
bone
*Usually survive
into adulthood
*Both are more
common in
Ashekenazi Jews
Niema Mtations in Cholesterol *More common
n-Pick NPC1 and 2 than A and B
Diseas gene combined
e Type (95% is due *NPC is clinically
C to NPC1) heterogeneous. It
may present
(Unlike as hydrops fetalis
most other and stillbirth, as
storage neonatal hepatitis,
diseases, or,
product of most commonly, as
NPC gene is a chronic form
not an characterized by
enyme. NPC progressive
is due to a neurologic damage
primary *difficulty
defect in coordinating
nonenzymati movements
c lipid (ataxia)
transport.) *an inability to
move the eyes
vertically
(vertical
supranuclear
gaze palsy)
*poor muscle tone
(dystonia)
*severe liver
disease
*interstitial lung
disease. *problems
with speech and
swallowing that
worsen over time,
 eventually
interfering with
feeding.
Gauch Glucocerebr Glucocerebr Type 1: *Type 1: chronic *Most
ers osidase oside monon non-neuronopathic common
Diseas (also known uclear form (99%) Lysosomal
e as Beta phagoc *Spleen can be up Storage
(AR) Glucosidase) ytes to 10kg in some Disorder
throug (patient presents *Replacem
hout with distended ent therapy
body, belly) with
esp *Pancytopenia/th recombina
liver rombocytopenia nt enzymes
and secondary to is the
spleen hypersplenism mainstay
witho => can present for
ut as anemia/fatgue treatment;
involvi and easy bruising it is
ng effective,
brain *fractures and bone and those
pain can occur due with type I
to expansion of the disease can
Type 2 marrow space expect
and 3: *aseptic necrosis of normal life
heads of long expectancy
bones / Erlenmeyer with this ;
flask deformity of extremely
the distal femur expensive.
*Skin pigment
changes: Grey-
brown * <15% of
pigmentation of mean normal
forehead, hands glucocerebro
and pretibial area sidase
 *Life span is activity in
shortened but not peripheral
markedly blood
*Type 1 occurs leukocytes is
diagnostic
more often in
Note:
Ashkenazi Jews enzyme
activity in
carriers
*Type 2: Acute (heterozygote
neuropathic s) is generally
*Extensive and half-normal,
progressive but may
neurological overlap with
healthy
damage
controls
*Usually die by age
two
* virtually no
detectable
glucocerebrosidase
activity

*Type 3: Chronic
neuropathic
*slower,
progressive
neurological
symptoms
*Types 2 and 3
have no association
with Ashkenazi
Jews
Krabbe Galactocere Galactocere
s brosidase brosides
Diseas (GALC)
e (Also known Psychosine
(AR) as b-
Galactosidas
e)
(Galactosylc
eramidase)