Mitochondrial Membrane Protein-Associated Neurodegeneration Mimicking Juvenile Amyotrophic Lateral Sclerosis.
Mitochondrial membrane protein associated neurodegeneration (MPAN) is the third most common subtype of neurodegeneration with brain iron accumulation (NBIA) and caused by mutations of the orphan gene C19ORF12 encoding a transmembrane mitochondrial protein. Like other NBIA disorders, the hallmark of neuropathology is iron deposition in the basal ganglia, but the clinical presentation is highly variable.



We present the relevant clinical history, neurological examination, electrophysiological and neuroimaging tests of a currently ten-year-old girl. The genetic analysis was carried out by exome sequencing focused on known NBIA and juvenile amyotrophic lateral sclerosis (ALS) genes.



The patient presented at four years of age with progressive lower extremity weakness and generalized hypotonia. She was initially diagnosed with juvenile ALS based on clinical signs, negative brain magnetic resonance imaging (MRI) and electromyography findings. As the disease progressed, a repeat brain MRI showed iron deposition in the basal ganglia at nine years of age. Exome sequencing of genes known to be associated with NBIA revealed a compound heterozygous mutation of C19ORF12 gene.



A C19orf12 gene mutation should be considered in young children with clinical signs of progressive upper and lower motor neuron disease. Finding iron accumulation in the basal ganglia helps to focus the genetic testing, but it may not be apparent for several years.
University of Connecticut School of Medicine, Farmington, Connecticut.
Jiyeon
J
Kim
Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut.
Yu-Hsien
YH
Liao
Yale Children's Hospital, New Haven, Connecticut.
Cristian
C
Ionita
Yale University School of Medicine, New Haven, Connecticut.
Allen E
AE
Bale
Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Basil
B
Darras
Children's Medical Center, University of Connecticut, Farmington, Connecticut. Electronic address: gacsadi@connecticutchildrens.org.
Gyula
G
Acsadi
D001921:Brain / Q000000981:diagnostic imaging; D002648:Child; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D024101:Mitochondrial Proteins / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy
C568481:C19orf12 protein, human; D024101:Mitochondrial Proteins
ALS; C19ORF12; MPAN; iron deposition; neurodegeneration