title: A novel type of familial proximal axonal dystrophy: three cases and a review of the axonal dystrophies.
abstract: Three related infants of Roma ancestry, two of them siblings, showed hypotonia, predominantly axial, from birth, difficulty swallowing, myoclonic seizures, and respiratory difficulty. Dysmorphic features, principally micrognathia were present. EEGs showed focal epileptiform abnormalities. All three died in their 5th month from respiratory insufficiency complicated by pneumonia. Autopsy showed small brains without malformation. Microscopy revealed numerous axonal spheroids involving particularly the brain stem and spinal cord, with especial prominence in the middle cerebellar peduncle, the anterior part of the thalamic reticular nuclei, and the anterior horns and columns of the spinal cord. Spheroids that appeared to be on axons of lower motor neurons were especially large. No spheroids were seen in peripheral nerves; electron microscopy did not show spheroids in skin. By electron microscopy spheroids contained neurofilaments, sparse mitochondria, and electron dense granules. The material did not allow identification of microtubules. Closely packed vesicles excluded neurofilamanets from the center of many spheroids, especially in the middle cerebellar peduncle. Sprouting of axons from the surface of many spheroids was seen. This disease is distinct from the well described type of infantile neuroaxonal dystrophy (Seitelberger's disease) in view of the distribution of spheroids, presence of spheroids on proximal rather than distal parts of axons, sparing of the peripheral nerves, lack of staining for synuclein, presence of sprouting, and lack of membranous profiles in the spheroids. A review of reported types of axonal dystrophy has not shown identical cases.
authors.affiliation: Department of Anatomic Pathology, Hospital São Joâo, Alameda Professor Hernani Monteiro, Porto 4200, Portugal. stirling.carpenter@gmail.com
authors.forename: Stirling
authors.initials: S
authors.lastname: Carpenter
authors.forename: Henrique
authors.initials: H
authors.lastname: Soares
authors.forename: Otília
authors.initials: O
authors.lastname: Brandão
authors.forename: Conceição
authors.initials: C
authors.lastname: Souto Moura
authors.forename: Lígia
authors.initials: L
authors.lastname: Castro
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Rodrigues
authors.forename: Ana Luisa
authors.initials: AL
authors.lastname: Cunha
authors.forename: Carla
authors.initials: C
authors.lastname: Bartosch
mesh_terms: D001921:Brain / Q000473:pathology*; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008854:Microscopy, Electron; D019150:Neuroaxonal Dystrophies / Q000473:pathology* / Q000503:physiopathology; D010375:Pedigree; D006178:Romani People; D035781:Siblings; D013116:Spinal Cord / Q000473:pathology*