Inheritance of PEBEL2
PEBEL is an autosomal recessive disorder, and this condition can be passed down from both parents to the affected individual. Affected individuals inherit two copies of the gene mistake specifically in the NAXD gene, one from each of their parents. The unaffected parents have one copy with the mistake and one normal copy, and usually do not show signs of the disorder and are asymptomatic.
NAXD gene mistakes
PEBEL2 is caused by ‘mistakes’ in the NAXD gene. The NAXD gene ‘mistakes’ result in the NAXD protein either being absent, or not functioning properly.
The NAXD protein is critical for repairing damaged molecules in the body. When the NAXD protein doesn’t repair these damaged molecules, they accumulate and have a toxic effect.
Diagnostic testing
PEBEL2 can be diagnosed by genetic testing to detect NAXD gene mistakes.
Genetic testing is suggested in children with rapidly deteriorating brain function, skin lesions, muscle weakness, seizures and/or heart conditions, particularly if their condition occurred after an illness, fever, or injury.
Genetic testing can be by targeted single gene sequencing, multi-gene panels, whole exome or genome sequencing and/or RNA sequencing.
NAXD