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Washington University Experience | NEURODEGENERATION | Infantile Neuroaxonal Dystrophy (INAD) | 2J Comment
Final Neuropathologic Diagnosis: Infantile neuroaxonal dystrophy (Seitelberger's disease). ---- Comment: INAD may represent a central-peripheral distal axonopathy or dying-back neuropathy. Resemblance of these lesions to the localized axonal dystrophy involving the gracile and cuneate nuclei of animals and man with presumed vitamin E deficiency prompted the unsuccessful attempt to reverse this disease in a few cases of INAD with vitamin E therapy, even though no abnormalities in vitamin E levels have been demonstrated in INAD. Pigment deposition in the putamen in this case stimulates comparison with PKAN, previously known as Hallervorden-Spatz disease, an autosomal recessive condition caused by mutations in the PANK2 gene, that encodes the enzyme pantothenate kinase, which causes problems with vitamin B5 (pantothenate) metabolism. In PKAN many clinical and pathological differences exist when compared to classical INAD. Differences exist in the age of onset (younger in INAD), course (shorter in INAD), clinical findings (typically hypotonia without movement disorder in INAD and rigidity and extrapyramidal signs in PKAN) and greater frequency of familial cases in INAD. Neuropathological findings typically show generalized involvement of the PNS and CNS in INAD compared to the restricted involvement of the substantia nigra and globus pallidus in PKAN; absent, minimal or inconstant pigmentation of the basal ganglia in INAD vs. prominent pigment deposition in the substantia nigra and globus pallidus in PKAN. Profound cerebellar and optic atrophy characterizes INAD and is of much lesser severity in PKAN. PKAN & INAD are now separate entities but histopathology demonstrated a continuum of cases between the classic presentations of PKAN and INAD in which neuropathologic and clinical findings are intermediate or combinations of the classical presentations, suggesting a possible relationship between the two. It is interesting in this regard that within any single family, the clinical and pathologic presentations are quite similar as in this family.
