Researchers show early developmental delays predict poor long-term
outcomes in Leigh syndrome patients
Study makes the case for Leigh syndrome to be considered a potential
diagnosis for infants and children with early developmental delays

Date:
March 1, 2022
Source:
Children's Hospital of Philadelphia
Summary:
Researchers have found that developmental delays associated
with Leigh syndrome, the most common pediatric mitochondrial
disorder, may occur earlier than previously recognized -- even
before metabolic stroke and regression -- which could provide
clinicians with an opportunity for earlier diagnosis and therapeutic
interventions.



FULL STORY ========================================================================== Researchers from the Mitochondrial Medicine Frontier Program at Children's Hospital of Philadelphia (CHOP) have found that developmental delays
associated with Leigh syndrome, the most common pediatric mitochondrial disorder, may occur earlier than previously recognized -- even before
metabolic stroke and regression -- which could provide clinicians with
an opportunity for earlier diagnosis and therapeutic interventions. The findings were recently published online by the journal Molecular Genetics
and Metabolism.


========================================================================== Leigh syndrome has been characterized by neurodevelopmental regression,
when a child loses previously achieved skills and developmental
milestones, with metabolic strokes occurring in their deep brain regions typically early in life. Currently, no FDA-approved therapies or cures
exist, and developmental delays associated with Leigh syndrome are often
the primary symptom studied in clinical trials.

Historically, developmental disabilities were thought to mainly occur
after the onset of metabolic stroke and neurologic regression. However,
some rare instances have been reported in which primary developmental
delays occurring prior to neurologic regression were observed in Leigh
syndrome patients. The CHOP researchers decided to examine existing data
to see if primary developmental delays were more common than previously believed.

"By looking at the pre-regression history of these patients, we were
hoping to see signs that would allow us to diagnose Leigh syndrome at an earlier stage prior to their acute decompensation," said co-senior author Rebecca Ganetzky, MD, an attending physician, Assistant Professor, and
Director of Biochemical Test Development in the Mitochondrial Medicine
Frontier Program at CHOP. "Since we found that developmental delays were
the presenting symptom for many of these cases, our study demonstrates
that mitochondrial energetics impact developmental trajectories prior
to their first episode of neurodevelopmental regression." Among a
cohort of 69 Leigh syndrome patients, 47 had a history of primary
developmental delays prior to any regression and 53 had neurodevelopmental regression. The study team identified three distinct phenotypes among
these patients: those with primary developmental delays followed by
regression (31 patients), primary developmental delays without subsequent regression (16 patients), and regression without primary developmental
delays (22 patients).

Those with a history of primary developmental delays were more likely
to have earlier disease onset and worse long-term educational outcomes.

"This study demonstrates that Leigh syndrome disorders should
be considered a diagnostic possibility at the time when a child is
recognized to have early developmental delays, even if the child
hasn't yet had a serious regression episode that is often the trigger
to begin the diagnostic process," said study co-author Marni Falk, MD,
an attending physician, Professor, Distinguished Chair, and Executive
Director of the Mitochondrial Medicine Frontier Program at CHOP. "We
hope our findings will lead to prospective natural history studies
that examine specific neurodevelopmental outcomes to help us design
future clinical trials for therapies to help these patients at as
early a stage in their disease course as possible." This study was
supported by the North American Mitochondrial Disease Consortium (NAMDC) Gateway to Mitochondrial Medicine Grant from the United Mitochondrial
Disease Foundation, the CHOP Mitochondrial Medicine Frontier Program,
the National Institutes of Health grants K08-DK113250, R35-GM134863,
and the Intellectual and Developmental Disabilities Research Center at CHOP/UPENN per NIH/NICHD grants P50 HD105354 and U54-HD086984.

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========================================================================== Journal Reference:
1. Rory J. Tinker, Marni J. Falk, Amy Goldstein, Ibrahim George-Sankoh,
Rui
Xiao, Laura Adang, Rebecca Ganetzky. Early developmental delay
in Leigh syndrome spectrum disorders is associated with poor
clinical prognosis.

Molecular Genetics and Metabolism, 2022; DOI:
10.1016/j.ymgme.2022.02.006 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220301152334.htm

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