A novel ferritin light chain mutation in neuroferritinopathy with an atypical presentation.
Neuroferritinopathy or hereditary ferritinopathy is an inherited neurodegenerative disease caused by mutations in ferritin light chain (FTL) gene. The clinical features of the disease are highly variable, and include a movement disorder, behavioral abnormalities, and cognitive impairment. Neuropathologically, the disease is characterized by abnormal iron and ferritin depositions in the central nervous system. We report a family in which neuroferritinopathy begins with chronic headaches, later developing progressive orolingual and arm dystonia, dysarthria, cerebellar ataxia, pyramidal tract signs, and psychiatric symptoms. In the absence of classic clinical symptoms, the initial diagnosis of the disease was based on magnetic resonance imaging studies. Biochemical studies on the proband showed normal serum ferritin levels, but remarkably low cerebrospinal fluid (CSF) ferritin levels. A novel FTL mutation was identified in the proband. Our findings expand the genetic and clinical diversity of neuroferritinopathy and suggest CSF ferritin levels as a novel potential biochemical marker for the diagnosis of neuroferritinopathy.
Department of Neurology, National Hospital Organization Hyogo-Chuo National Hospital, 1314 Ohara, Sanda 669-1592, Japan. Electronic address: nishida@hch.hosp.go.jp.
Katsuya
K
Nishida
Department of Pathology & Laboratory Medicine, Indiana University School of Medicine, 635 Barnhill Drive MS A174, Indianapolis, IN 46202, USA.
Holly J
HJ
Garringer
Department of Neurology, National Hospital Organization Hyogo-Chuo National Hospital, 1314 Ohara, Sanda 669-1592, Japan.
Naonobu
N
Futamura
Department of Neurology, National Hospital Organization Hyogo-Chuo National Hospital, 1314 Ohara, Sanda 669-1592, Japan.
Itaru
I
Funakawa
Department of Neurology, National Hospital Organization Hyogo-Chuo National Hospital, 1314 Ohara, Sanda 669-1592, Japan.
Kenji
K
Jinnai
Department of Pathology & Laboratory Medicine, Indiana University School of Medicine, 635 Barnhill Drive MS A174, Indianapolis, IN 46202, USA. Electronic address: rvidal@iupui.edu.
Ruben
R
Vidal
Department of Neuropathology (The Brain Bank for Aging Research), Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae-cho, Itabashi City, Tokyo 173-0015, Japan; Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi City, Tokyo 173-0015, Japan.
Masaki
M
Takao
D000328:Adult; D001052:Apoferritins / Q000235:genetics*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D005293:Ferritins / Q000134:cerebrospinal fluid*; D006801:Humans; D019189:Iron Metabolism Disorders / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D019150:Neuroaxonal Dystrophies / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000235:genetics*; D059906:Neuroimaging; D010375:Pedigree; D063189:Symptom Assessment
D015415:Biomarkers; D005293:Ferritins; D001052:Apoferritins
Brain; Ferritin; Hereditary ferritinopathy; Iron; Neurodegeneration