PracticeUpdate: Conference Series - The Best of ICIEM 2017

Founder Mutation and NewDiagnostic Biomarker of PLA2G6-Associated Neurodegeneration Are Identified Two mutations associated with neurodegenerative disease: the founder mutation and a new diagnostic biomarker of PLA2G6-associated neurodegeneration (PLAN) have been identified in a large North African cohort, according to a new report.

I chraf Kraoua, MD, of the National Institute Mongi Ben Hamida of Neurology of Tunis, Tunisia, explained that mutations in the PLA2G6 gene cause PLAN, a spectrum of neurodegenerative conditions including infantile, childhood, and adult-onset forms. PLA2G6 encodes the group VI calcium-inde- pendent phospholipase A2, which hydrolyzes glycerophospholipids to lysophospholipids and free fatty acids. This enzyme is essential for membrane homeostasis and repair and for maintenance of mitochondrial membranes. “PLAN is often misdiagnosed,” Dr. Kraoua told PracticeUpdate . “We collected a large cohort in Tunisia but we were not able to confirm it molecu- larly. We collaborated with Enza Maria Valente, MD, PhD, of Casa Sollievo della Sofferenza-Mendel Institute, Rome. She gave us the opportunity to confirm our patients and then to discover the founder mutation, initially in 17 patients.” “After that, we considered this mutation the first in Tunisian patients diagnosed with PLAN, and we confirmed the remaining patients in Tunisia,” she added.

Thirty North African (26 Tunisian, three Algerian, and one Libyan) patients suspected clinically of suffering from infantile-onset PLAN underwent clinical, biological, neurophysiological, and neu- roimaging examinations and PLA2G6 sequencing. Twenty-nine children exhibited the commonest form of infantile-onset PLAN, with early onset of psychomotor regression, hypotonia, pyramidal and cerebellar signs, and abnormal ocular move- ments. The phenotype was highly homogeneous, with rapid development of severe spastic tetra- paresis, cognitive impairment, and optic atrophy. “Regarding the diagnostic biomarker,” Dr. Kraoua said, “we performed systematic routine biolog- ical screening for all patients. We discovered elevation in aspartate transaminase and high lactate dehydrogenase in all patients, even at an early stage. We also compared our results with an Italian cohort and they exhibited the same abnormalities.” Of 28 patients who underwent routine biochem- ical testing, all exhibited mildly increased levels of aspartate aminotransferase and lactate dehy- drogenase, even at early stages of the disease.

Dr. Ichraf Kraoua

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