title: Sustained therapeutic response to riboflavin in a child with a progressive neurological condition, diagnosed by whole-exome sequencing.
abstract: One of the most promising outcomes of whole-exome sequencing (WES) is the alteration of medical management following an accurate diagnosis in patients with previously unresolved disorders. Although case reports of targeted therapies resulting from WES have been published, there are few reports with long-term follow-up that confirm a sustained therapeutic response. Following a diagnosis by WES of Brown-Vialetto-Van Laere Syndrome 2 (BVVLS2), high-dose riboflavin therapy was instituted in a 20-mo-old child. An immediate clinical response with stabilization of signs and symptoms was noted over the first 2-4 wk. Subsequent clinical follow-up over the following 8 mo demonstrates not just stabilization, but continuing and sustained improvements in all manifestations of this usually fatal condition, which generally includes worsening motor weakness, sensory ataxia, hearing, and vision impairments. This case emphasizes that early application of WES can transform patient care, enabling therapy that in addition to being lifesaving can sometimes reverse the disabling disease processes in a progressive condition.
authors.affiliation: Department of Pediatrics, Division of Medical Genetics Duke University School of Medicine, Durham, North Carolina 27710, USA;
authors.forename: Vandana
authors.initials: V
authors.lastname: Shashi
authors.affiliation: Institute for Genomic Medicine, Columbia University, New York, New York 10032, USA;; Department of Medicine, The University of Melbourne, Austin Health and Royal Melbourne Hospital, Melbourne, 3050 Victoria, Australia;
authors.forename: Slavé
authors.initials: S
authors.lastname: Petrovski
authors.affiliation: Department of Pediatrics, Division of Medical Genetics Duke University School of Medicine, Durham, North Carolina 27710, USA;
authors.forename: Kelly
authors.initials: K
authors.lastname: Schoch
authors.affiliation: Department of Pediatrics, Division of Medical Genetics Duke University School of Medicine, Durham, North Carolina 27710, USA;
authors.forename: Rebecca
authors.initials: R
authors.lastname: Crimian
authors.affiliation: Division of Physical Therapy, Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA;
authors.forename: Laura E
authors.initials: LE
authors.lastname: Case
authors.affiliation: Department of Pediatrics, Division of Neurology, Duke University School of Medicine, Durham, North Carolina 27710, USA;
authors.forename: Roha
authors.initials: R
authors.lastname: Khalid
authors.affiliation: Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina 27710, USA;
authors.forename: Maysantoine A
authors.initials: MA
authors.lastname: El-Dairi
authors.affiliation: Department of Pediatrics, Division of Medical Genetics Duke University School of Medicine, Durham, North Carolina 27710, USA;; Department of Neurobiology, Duke University, Durham, North Carolina 27710, USA.
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Jiang
authors.affiliation: Department of Pediatrics, Division of Neurology, Duke University School of Medicine, Durham, North Carolina 27710, USA;
authors.forename: Mohamad A
authors.initials: MA
authors.lastname: Mikati
authors.affiliation: Institute for Genomic Medicine, Columbia University, New York, New York 10032, USA;
authors.forename: David B
authors.initials: DB
authors.lastname: Goldstein
keywords: drooling; gait imbalance; neurodegeneration; seesaw nystagmus; upper motor neuron abnormality