Myoadenylate deaminase (AMPD) deficiency
Background Histopathology & Immunohistochemistry Reference
BACKGROUND AND CLINICAL INFORMATION:
Head
Incidence: This is the most common enzyme deficiency being
found in muscle biopsies. The prevalence is (2-3 %).
Clinical
features: In general,
it is heterogeneous. The primary form is resulted from mutation of the AMPD1
gene and the symptomatology is not impressive. The significance of isolated AMPD
deficiencyThe secondary or acquired form is probably the carrier form of this
disease. Impressive clinical manifestations may be triggered by an associated
myopathy such as McArdle’s disease and carnitine palmitoyltranferase
deficiency.
During
exercise, MAD
catalyses the deamination of AMP into IMP and ammonia. IMP can subsequently be
re-aminated to AMP.
Biochemistry: Myoadenylate deaminase is the muscle-specific
isoform of adenylate deaminase. In
cases of MAD deficiency, muscle biopsies are histologically normal but no
myoadenylate deaminase can be demonstrated by staining. IMP formation is
strongly diminished, and consequently the purine nucleotide cycle is disrupted,
which affects muscle metabolism during exercise.
Molecular
pathology: Most of the
MAD deficiency is caused by a common homozygous point mutation (C34T) in the
second exon of the AMPD1 gene. This mutation generates a stop codon and lead to
the production of a truncated protein.
HISTOPATHOLOGY AND IMMUNOHISTOCHEMISTRY:
Head
Histology
of the muscle is histologically normal but no myoadenylate deaminase can be
demonstrated by staining.
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HT et al., Ann Neurol 1998 Jul;44(1):140-3
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