title: Optico-cochleo-dentate degeneration associated with severe peripheral neuropathy and caused by peroxisomal D-bifunctional protein deficiency.
abstract: The clinical, neuroradiological, neuropathological and biochemical findings in a patient with optico-cochleo-dentate degeneration (OCDD; OMIM 258700) are presented in a severe case succumbing at the age of 4 years. The electron microscopic and biochemical data showed for the first time that OCDD may occur as the phenotypic expression of D-bifunctional protein deficiency, i.e., a peroxisomal disorder. The boy was born as the first child of healthy, consanguineous parents of Turkish origin. No other family members were affected. The main clinical symptoms consisted of muscle hypotonia ("floppy infant"), generalized epileptic fits, hypacusis, rotatory nystagmus, insufficient pupillary reactions, and mental retardation. Fibroblast cultures revealed D-bifunctional protein deficiency. Neuropathological examination displayed moderate frontoparietal and insular microgyria, and atrophy of the cerebellum. Loss of neurons was severe in the granular layer, the Purkinje cell band of the cerebellum, and rather complete in the dentate nucleus. A corresponding loss of myelinated fibers associated with characteristic periodic acid-Schiff-positive macrophages was most prominent in the white matter of the cerebellum. There was additional severe loss of myelinated fibers in the central portions of the optic nerve, reduction of the nerve fiber density in the cochlear nerve, and reduction of myelinated nerve fibers by about 80-90% in the sural nerve, which has not been studied in previous cases. At the electron microscopic level, characteristic inclusions mainly in perivascular macrophages and astrocytes were the most prominent finding. The inclusions usually showed a bilaminar structure, whereas trilaminar structures, typically seen in adrenoleukodystrophy, and multilaminar structures were less frequently seen.
authors.affiliation: Department of Neuropathology, University Hospital, RWTH Aachen, Pauwelsstr. 30, 52074 Aachen, Germany. jmschroder@ukaachen.de
authors.forename: J M
authors.initials: JM
authors.lastname: Schröder
authors.forename: V
authors.initials: V
authors.lastname: Hackel
authors.forename: R J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: G
authors.initials: G
authors.lastname: Göhlich-Ratmann
authors.forename: T
authors.initials: T
authors.lastname: Voit
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency*; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D016022:Case-Control Studies; D002526:Cerebellar Diseases / Q000150:complications* / Q000473:pathology; D002529:Cerebellar Nuclei / Q000473:pathology / Q000648:ultrastructure; D002675:Child, Preschool; D003056:Cochlear Nerve / Q000473:pathology / Q000648:ultrastructure; D004746:Enoyl-CoA Hydratase / Q000172:deficiency*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007535:Isomerases / Q000172:deficiency*; D008297:Male; D008854:Microscopy, Electron; D009097:Multienzyme Complexes / Q000172:deficiency*; D009900:Optic Nerve / Q000473:pathology / Q000648:ultrastructure; D010523:Peripheral Nervous System Diseases / Q000150:complications* / Q000473:pathology; D063994:Peroxisomal Bifunctional Enzyme; D018901:Peroxisomal Disorders / Q000150:complications*; D020675:Peroxisomes / Q000378:metabolism; D011180:Postmortem Changes; D013497:Sural Nerve / Q000473:pathology / Q000648:ultrastructure; D000160:Vestibulocochlear Nerve Diseases / Q000150:complications* / Q000473:pathology; D000097382:CD68 Molecule
chemical_list: D015094:3-Hydroxyacyl CoA Dehydrogenases; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D004746:Enoyl-CoA Hydratase; D007535:Isomerases; D009097:Multienzyme Complexes; D063994:Peroxisomal Bifunctional Enzyme; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C576253:EHHADH protein, human