Association of Infantile Neuroaxonal Dystrophy and Osteopetrosis: A Rare Autosomal Recessive Disorder

Abstract

The association of neuroaxonal dystrophy and osteopetrosis is reported in 2 siblings born to non-consanguineous parents. The 1 st child was diagnosed as having infantile osteopetrosis shortly after delivery. A computed tomography scan of the head revealed agenesis of the corpus callosum. She died at the age of 9 months. Post-mortem examination showed pneumonia and bony sclerosis. Neuropathological examination revealed cerebral atrophy, ventricular dilation, absence of the corpus callosum, and a small hippocampus. Neuroaxonal spheroids were found in hippocampus, basal ganglia, pons, medulla, spinal cord, cranial nerves, cerebellum, and peripheral nerves. Ultrastructural examination revealed membranous cytoplasmic bodies and electron-dense granular deposits within the neuroaxonal spheroids as well as the soma of neurons. The 2nd child was delivered at 36 weeks of gestation because of intrauterine fetal distress. The diagnosis of osteopetrosis and partial agenesis of the corpus callosum was made shortly after delivery. The child died at 1 month without an autopsy. There are rare cases reported previously with the association of neuroaxonal dystrophy and osteopetrosis. We review these cases and compare them with ours.

Importance of neurological assessment before bone marrow transplantation for osteopetrosis

“…Although the visual loss has usually been attributed solely to optic atrophy secondary to bony compression of the optic nerve, it can be caused by primary retinal degeneration, either isolated or as a part of a progressive generalised neurodegenerative disorder 13 4In some children, the association of osteopetrosis with neuronal ceroid lipofuscinosis has been documented,4 and in others osteopetrosis was associated with infantile neuroaxonal dystrophy 3…”

Infantile neuroaxonal dystrophy (Seitelberger's disease)

“…This may be caused by gene deletions or duplications or other such impairments. 6 Diagnostic findings A conclusive diagnosis of IND is made by the histological study of brain, nerve and muscle, skin, or conjunctival 7 biopsy showing axonal spheroids. Biopsies of the nerve and muscle should be performed as soon as there is a suspicion of the disease.…”

Distrofia neuroaxonal infantil: relato de dois casos

“…A biópsia do músculo biceps braquial, o qual é frequentemente acessado para o diagnós-tico de doenças neuromusculares, geralmente possui nervos periféricos e junções neuromusculares abundantes, podendo desta forma contribuir para o diagnóstico [7][8][9][10] . A ressonância nuclear magnética não possui sensibilidade nem especificidade para o diagnóstico, porém descreve-se o achado de hiperintensidade difusa do córtex cerebelar, devido a astrogliose e a perda neuronal extensa que ocorre nessa doença 11 . Os dois casos descritos mostram as manifestações clínicas comumente encontradas, como o atraso do desenvolvimento psicomotor, atrofia com fraqueza muscular, hiperreflexia e desordem visual 1 .…”

“…Portanto, o conjunto de achados clínicos característicos e o achado de esferóides neuroaxonais típicos na biópsia cortical ou periférica permite que o diagnóstico presuntivo seja feito ainda durante a vida 11 .…”