Carrier rate in Iranian Jews:
Approximately 1 in 10

Disease frequency:
Approximately 1 in 400 Iranian Jews are affected.

Carrier rate in the general population:
Rare

Other ethnic groups in which it occurs:
Most common in people of European descent; rare in Asians

Inheritance:
Autosomal recessive

Age of onset of symptoms:
This condition is recognized only when paralysis of the respiratory and other skeletal muscles fails to spontaneously resolve after succinylcholine or other related agent is administered as an adjunctive paralytic agent during anesthesia procedures.

Symptoms:
When anesthetic drugs such as succinylcholine or mivacurium are administered to a susceptible person, the muscles that work the lungs may become paralyzed. Sometimes patients under anesthesia who are undergoing surgery do not wake-up after surgery or lie awake and paralyzed.

Average lifespan:
With early detection and careful dietary control, normal growth and development are possible.

What causes the features of the disease:
There are inherited and acquired causes of the pseudocholinesterase deficiency.

The inherited form of the condition is caused by mutations (changes) in the genes that produce pseudocholinesterase. The mutations cause the gene to produce inadequate amounts of pseudocholinesterase or to produce abnormal forms of the enzyme causing the effects of prolonged duration of paralysis or anesthesia.

The acquired causes of pseudocholinesterase deficiency include the following: chronic infections, extensive burn injuries, liver disease, cancer, malnutrition, and taking certain medications.

Treatment or management:
Individuals with pseudocholinesterase deficiency should avoid exposure to exogenous (outside of the body) sources of choline esters. The mainstay of treatment for patients in the midst of prolonged paralysis is mechanical ventilatory support until respiratory muscle paralysis spontaneously resolves. Recovery eventually occurs as a result of passive diffusion of succinylcholine away from the neuromuscular junction.

Carrier testing - number of mutations screened for and detection rate in the Iranian Jewish population:
The gene that codes for the pseudocholinesterase enzyme is located at the E1 locus on the long arm of chromosome 3, and 96% of the population is homozygous for the normal pseudocholinesterase genotype, which is designated as EuEu.
The remaining 4% of the population carries one or more of the following atypical gene alleles (Ea, Ef, or Es)for the pseudocholinesterase gene in either a heterozygous or homozygous fashion.

Other testing information:
Although the diagnosis is suspected after an episode of prolonged respiratory paralysis following administration of succinylcholine, the diagnosis of pseudocholinesterase deficiency is confirmed by plasma assays of pseudocholinesterase enzyme activity. A simplified screening test of pseudocholinesterase enzyme activity can be performed using the Acholest Test Paper.

Current research:
Further research is being done to determine the effects of choline anesthetic agents and possible drugs that may act to reverse their effects (e.g. Sugammadex).

For more information:
Genetic and Rare Diseases (GARD) Information Center:
   rarediseases.info.nih.gov
   www.genome.gov
NIH/National Institute of General Medical Sciences:
   www.nigms.nih.gov