TY - JOUR
T1 - Diagnosis by whole exome sequencing of atypical infantile onset Alexander disease masquerading as a mitochondrial disorder
AU - Nishri, Daniella
AU - Edvardson, Simon
AU - Lev, Dorit
AU - Leshinsky-Silver, Esther
AU - Ben-Sira, Liat
AU - Henneke, Marco
AU - Lerman-Sagie, Tally
AU - Blumkin, Lubov
N1 - Funding Information:
This work has been supported by a trilateral grant from the German Research Foundation ( Ga354/9-1 ).
PY - 2014/7
Y1 - 2014/7
N2 - Introduction There are many similarities, both clinical and radiological, between mitochondrial leukoencephalopathies and Alexander disease, an astrogliopathy. Clinically, both can manifest with a myriad of symptoms and signs, arising from the neonatal period to adulthood. Radiologically, both can demonstrate white matter changes, signal abnormalities of basal ganglia or thalami, brainstem abnormalities and contrast enhancement of white matter structures. Magnetic resonance spectroscopy may reveal elevation of lactate in the abnormal white matter in Alexander disease making the distinction even more challenging. Patient and Methods We present a child who was considered to have an infantile onset mitochondrial disorder due to a combination of neurological symptoms and signs (developmental regression, failure to thrive, episodic deterioration, abnormal eye movements, pyramidal and cerebellar signs), urinary excretion of 3-methyl-glutaconic acid and imaging findings (extensive white matter changes and cerebellar atrophy) with a normal head circumference. Whole exome sequence analysis was performed. Results The child was found to harbor the R416W mutation, one of the most prevalent mutations in the glial fibrillary acidic protein (GFAP) gene that causes Alexander disease. Conclusions Alexander disease should be considered in the differential diagnosis of infantile leukoencephalopathy, even when no macrocephaly is present. Next generation sequencing is a useful aid in unraveling the molecular etiology of leukoencephalopathies.
AB - Introduction There are many similarities, both clinical and radiological, between mitochondrial leukoencephalopathies and Alexander disease, an astrogliopathy. Clinically, both can manifest with a myriad of symptoms and signs, arising from the neonatal period to adulthood. Radiologically, both can demonstrate white matter changes, signal abnormalities of basal ganglia or thalami, brainstem abnormalities and contrast enhancement of white matter structures. Magnetic resonance spectroscopy may reveal elevation of lactate in the abnormal white matter in Alexander disease making the distinction even more challenging. Patient and Methods We present a child who was considered to have an infantile onset mitochondrial disorder due to a combination of neurological symptoms and signs (developmental regression, failure to thrive, episodic deterioration, abnormal eye movements, pyramidal and cerebellar signs), urinary excretion of 3-methyl-glutaconic acid and imaging findings (extensive white matter changes and cerebellar atrophy) with a normal head circumference. Whole exome sequence analysis was performed. Results The child was found to harbor the R416W mutation, one of the most prevalent mutations in the glial fibrillary acidic protein (GFAP) gene that causes Alexander disease. Conclusions Alexander disease should be considered in the differential diagnosis of infantile leukoencephalopathy, even when no macrocephaly is present. Next generation sequencing is a useful aid in unraveling the molecular etiology of leukoencephalopathies.
KW - Alexander disease
KW - Lactic acid
KW - Leukoencephalopathy
KW - Mitochondrial disorders
UR - http://www.scopus.com/inward/record.url?scp=84903200255&partnerID=8YFLogxK
U2 - 10.1016/j.ejpn.2014.03.009
DO - 10.1016/j.ejpn.2014.03.009
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C2 - 24742911
AN - SCOPUS:84903200255
SN - 1090-3798
VL - 18
SP - 495
EP - 501
JO - European Journal of Paediatric Neurology
JF - European Journal of Paediatric Neurology
IS - 4
ER -