Myoadenylate Deaminase

Deficiency
Group 9: Ghising, Orquia, Reyes, Sangalang, Salvador

Myoadenylate Deaminase Deficiency

A metabolic

muscle disease that interferes with the

muscle cell's processing ofadenosine triphosphate(ATP)

Autosomal
Mutations

recessive genetic metabolic disorder

in the AMPD1 gene cause AMP deaminase

deficiency.

Three types:
Inherited

type

mutation in both copies of the AMPD1 gene in each cell

Acquired

type

decreased levels of AMP deaminase due to the

presence of a muscle or joint condition
Coincidental

inherited type

mutation in both copies of the AMPD1 gene and have a

separate joint or muscle disorder

Signs and
Symptoms

Fatigue
Without myoadenlyate deaminase

Heavy activity causes adenosine to be released into

cells or perfused into the surrounding tissues

Signals muscle fibers to feel FATIGUE

Muscle Pain
Due

to the high levels of lactate.

Increased

in adenosine temporarily decreased

pain, allowing over exertion without awareness.

Over

exertion causes rhabdomyolysis which is

painful.

Muscle Cramping
Related

to elevated Lactate.

Increased

calcium signaling across the SR caused

membrane instability from decreased levels of
ATP.

Muscle Weakness
Progressive

effects of chronic muscle damage

from rhabdomyolysis causes weakness

Long

term metabolic effects may result to NERVE

DAMAGE.

Pathophysiology/
Biochemical
Pathways
affected

Purine Nucleotides
Catabolism

Salvage Pathway of
Purine Nucleotides

Purine Nucleotide Cycle

Increases in muscle
activity create a demand
for an increase in the TCA
cycle, in order to generate
more
NADH
for
ATP
production.
Muscle replenishes TCAcycle intermediates in the
form
of
fumarate
generated by the purine
nucleotide cycle.

The generation of fumarate provides skeletal

muscles with its' only source of anapleurotic
substrate for the TCA cycle.
In order for continued operation of the cycle
during exercise, muscle protein must be
utilized to supply the amino nitrogen for the
generation of aspartate, which occurs by the
standard
transamination
reactions
that
interconvert amino acids with -ketoglutarate
to form glutamate and glutamate with
oxaloacetate to form aspartate.

Myodenylate Deaminase
exists in a unique isoenzymatic form in skeletal
muscle and appears to provide the rate limiting
step for entry in the purine nucleotide cycle

necessary for regeneration of inosine

monophosphate (IMP) and ultimate repletion of
adenosine triphosphate (ATP)

plays a role in the overall extraction of energy

stored in the adenine nucleotide pool and to
prevent accumulation of AMP and its attendant
influence on other metabolic pathways

Metabolic effects of AMP deaminase

removal of AMP formed during exercise, in order to favor
the formation of ATP from ADP by myokinase (adenylate
kinase)

release of NH3 and IMP, both stimulators of glycolysis

and hence of energy production

production of fumarate, an intermediate of the Citric Acid

Cycle, which also yields energy. It has therefore been
proposed that the muscle dysfunction observed in primary
AM-DA deficiency is caused by impairment of energy
production for muscle contraction.

Effects of failure to deaminate

the AMP molecules
1. Significant amounts of AMP are lost from the cell
and the body
2. Ammonia is not freed when the cell does work
3. The level of IMP in the cell is not maintained

Diagnosis

Screening for the defect can be performed by an

exercise test . A several-fold elevation of venous
plasma ammonia, seen in normal subjects, is
absent in AMP-DA deficiency.
Final diagnosis is established by histochemical or
biochemical assay in a muscle biopsy.

In the primary defect, the activity of AMP-DA is below 2% of normal,

and little or no immunoprecipitable enzyme is found.

In the secondary defect, the activity is 215% of normal, and usually

appreciable immunoreactivity is present .

In several large series of muscle biopsies for diagnostic purposes,

low enzyme activities were found in about 2% of patients.

Management

Management
D-ribose
serves as an additional source of energy for muscle, and is
only efficient as long as it is present in blood (short halflife)

Creatine

monohydrate

provides an alternative source of energy for anaerobic muscle

tissue by increasing the formation of adenosine triphosphate (ATP)