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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.
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.
Dr. Ichraf Kraoua
PRACTICEUPDATE CONFERENCE SERIES • ICIEM 2017
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