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Disorder
GALACTOSEMIA
Deficiency
GALT
(Galactose-1-Phosphate
Uridyltransferase)
GALK (Galactokinase)
GALE
(UDP-Galactose-4epimerase)
Description
Pathophysiology
Abnormal accumulation of
galactose and gal-1-p in
brain, liver, kidneys
Galactitol (lens of eyes)
AUTOSOMAL RECESSIVE
1:10,000 to 1:30,000
Clinical Features
Diagnosis
Management
Presence of reducing
substances in urine
Enzyme Assay in RBC, cord
blood and cultured
fibroblast
Measurement of
erythrocyte GALT activity
Molecular genetic testing
Cataracts if secondary to
galactitol accumulation is
reversible if lactose is
st
removed from diet within 1
3 months of life
Liver:
GSD 1, 3, 4, 6
Muscles:
GSD 5, 7, 10, 11, 12, 13
Both:
GSD 0 and 9
Generalized
Glycogenolysis: GSD 2
Newborn:
Vomiting, Hepatomegaly,
Cataracts
Biochemical Abnormalities:
Elevated blood
lactate
Pyruvate
Uric Acid
Cholesterol
TGC
Classical GAL (GALT Deficiency)
o Untreated
o Neonatal onset: multiple
systems
o Liver dysfunction,
coagulopathy, feeding and
weight loss, vomiting, lethargy
and hypotonia, renal
dysfunction,encephalopathy,
hemorrhage, E. coli sepsis
o Cataracts
o Ovarian failure (90%)
o Chronic brain effects (global
deficits, disability, etc.)
GALK deficiency:
o Cataracts and galactosemia
in otherwise healthy
Massive Hepatomegaly
Fasting Hypoglycemia
Lactic Acidosis
Physical features:
Short stature
Doll-like facies
Protuberant
abdomen
Lumbar lordosis
Complications: Renal Disease
and Liver Adenomas
Detection
- Detection of increased
Gal-1-P metabolites
- Enzyme studies (in serum,
Pompe Disease
AUTOSOMAL RECESSIVE
Epimerase deficiency:
o Partial deficiency
o Rarely, presents similarly
with GALT but with increase
or normal GALT enzyme
accumulation of excess glycogen
in nearly all cells
heart, muscles and nervous
tissue are predominantly
affected
profound hypotonia with
progressive muscle weakness
but with normal mentation
hypoglycemia and ketosis are
absent
cardiomyopathy and respiratory
difficulties are common in
infantile form
walking difficulties in late and
juvenile forms
individuals are not mentally
retarded
RBC)
- DNA mutation analysis
(research basis at
present)
Clinical Phenotypes:
Infantile-onset PD (IOPD)
severe hypotonia,
hepatomegaly,
hypertrophic
cardiomyopathy
barely survive beyond
toddler age
GAA activity: typically
<1% of normal
Later-onset PD (LOPD)
includes childhood onset
and adult onset
heterogenous clinical
manifestations
symmetric or asymmetric,
limb girdle, axial tongue,
facial
respiratory insufficiency
could occur early
Cardiac involvement rare
GAA activity: between 140% of normal mean
Reason seen by neurologist
is because of myopathy
Supportive
Enzyme Replacement
Therapy
recombinant human GAA
20 mg/kg/2 weeks IV
IOPD - prolongs survival
and ventilator-free period;
rescue the
cardiomyopathy
LOPD - improved
weakness and lung
function
more effective at
addressing
cardiomyopathy
Newborn Screening
enables early identification
and treatment
newborn with
lymphocyte/fibroblast
activity <5% of the normal
mean plus 2 identified
GAA gene mutations
without cardiac
involvement -LOPD
Regular follow-up
every 3-6 months
check for motor
development and serum
creatine kinase (CK)
start treatment if with
significant CK or motor
delay
Forbes Disease
Amylo-1,6 glucosidase
resulting in accumulation
of abnormally structured
glycogen having very short
outer chains in muscle and
liver
AUTOSOMAL RECESSIVE
Andersen Disease
McArdles Disease
Amylo-(1,4 to 1,6)
transglycosylase
(Debranching enzyme
deficiency)
o
death common
<3 years old
Muscle Phosphorylase
causing accumulation of
abnormal glycogen
Amylopectinosis
X-LINKED
Hers Disease
Liver Phosphorylase
AUTOSOMAL RECESSIVE
Tarui Disease
Muscle
phosphofructokinase
AUTOSOMAL RECESSIVE
Hepatomegaly, ketotic
hypoglycemia, hyperlipidemia,
variable skeletal myopathy,
cardiomyopathy and results in
short stature
The hepatic symptoms of GSDIII
usually resolve after puberty.
However, liver failure due to
cirrhosis may occur.
patients are well during the first
few months of life, later
nonspecific GI symptoms and
hepatosplenomegaly occurs
cirrhosis and portal
hypertension
Death will usually ensue by 5
years
Other manifestations:
o hypotonia
o muscle atrophy
o developmental delay
Attacks of myoglobinuria
frequently accompany the
muscle symptoms of GSDV
Exhibit burgundy colored urine
after exercise
S/Sx similar to GSD I & III but
milder
Liver biopsy
assay for branching enzyme
deficiency in muscle,
leukocytes, erythrocytes, or
fibroblasts can be carried out
to determine the exact
defect resulting in the
hepatomegaly
Maintenance of normal
blood glucose along with
adequate nutrient intake
both of which will improve
liver function and muscle
strength.
There is currently no
effective treatment for the
progressive cardiomyopathy