Adult polyglucosan body disease
Adult polyglucosan body disease
Description, Causes and Risk Factors:
Adult polyglucosan body disease (APBD) is a late-onset autosomal-recessive metabolic disorder due to deficiency of the glycogen branching enzyme (GBE). It occurs most frequently is due to a TYR329-SER mutation in the GBE gene. The disease is more common in Jewish Ancestry & Descents.
APBD is a very rare disorder that appears to affect males and females in about equal proportions. Familial clustering is observed in about 30% of cases.
Although the mechanism is not well understood, glycogen synthase may be chronically activated due to an associated energy de?cit limiting ATP (adenosine 5'-triphosphate) availability required for inactivation, by phosphorylation, of serine/threonine residues on the enzyme. If glycogen synthesis is unregulated, polyglucosan bodies would accumulate. Neural tissue is highly dependent on import of glucose from gluconeogenesis and glycogenolysis and ketone bodies from b-oxidation of fatty acids by the liver. Current thinking has favored "mechanical disruption" of cells by accumulating polyglucosan bodies as the main mechanism for the progressive symptomatology. However, it may be more appropriate to consider that a cellular energy de?cit due to inadequate normal glycogen reserves and unregulated glycogen synthase (GS) may be also relevant.
APBD is inherited autosomal recessively and genetic counseling can be given to those with the GBE1 gene mutations in the family. Pre-symptomatic testing can be performed if considered essential for genetic counseling.
The prognosis is variable depending on the severity of the disease and the level of care given to patients. In most cases it does not decrease life-expectancy but quality of life is most definitely affected.
The disorder is characterized bya gradual progression of involvement of both the central andperipheral nervous systems with a variable phenotype that oftenincludes pyramidal tetraparesis, sensory neuropathy in the lowerextremities, neurogenic bladder, and occasionally cognitiveimpairment. The disease progresses, relentlessly, from dif?cultywalking, impaired balance, progressive weakness, eventuallyinvolving the upper body, and can lead to early death.
Diagnosis is based on the presence of clinical manifestations of the disease along with the characteristic laboratory findings. Typically, MRI demonstrates cerebral white matter changes in the subcortical and periventricular areas, the posterior limb of the internal capsule and in the brainstem. Cerebral, cerebellar and spinal cord atrophy may also be seen at various stages of the disease. Reduced GBE activity is observed in cultured skin fibroblasts and peripheral blood lymphocytes of patients with APBD and sural nerve biopsy shows the presence of polyglucosan bodies in the nerve. Genetic testing is essential for the diagnosis and makes nerve biopsy unnecessary.Antenatal diagnosis can be performed but is rarely done as the disease has an adult onset.
Prevention of secondary complications: Gait aids to prevent falls and urologic management to prevent urosepsis.
Surveillance: Periodic assessment of bladder function, gait, sensation in the distal lower extremities, and cognition.
Currently, there is no effective therapy for recovery of function or relieving the progression of this disease. Similarly, there is very little information relative to primary or secondary abnormalities in intermediary metabolism. Treatment of adult polyglucosan body disease generally requires a Multidisciplinary approach and may include physicians, physical therapists, medical social workers, and nurses. Management focuses on use of gait safety devices; antispasmodic bladder medications and in-and-out bladder catheterization or an indwelling bladder catheter; behavioral modification and cognitive aids as needed.
NOTE: The above information is for processing purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.
DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.
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