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MRI in an unusually protracted neuronopathic variant of acid sphingomyelinase deficiency
J Obenberger1, Z Seidl, H Pavlů
1Department of Neurology, First Medical Faculty, Charles University, Prague, Czech Republic. joben@1f1.cuni.cz
Abstract:
MRI was performed in two siblings with the neuropathic sphingomyelinase deficiency caused by identical mixed heterozygosity in the structural acid sphingomyelinase gene. The clinical phenotype of the cases is unique in showing a rather protracted course, both having reached the fourth decade. Pronounced cerebellar and mild supratentorial atrophy was seen on MRI in both siblings, in contrast to their strikingly different clinical status. One has no overt neurological deficit, while the second had neocerebellar symptoms and signs, nystagmus and cranial nerve palsies for some years. The MRI findings, together with the cherry-red spot in the ocular fundus, ultrastructurally proved storage in cutaneous nerve Schwann cells and the histopathologically proven brain neuronal storage in a third sibling who died after a relatively rapid course dominated by fatal visceral storage, is evidence that a remarkably restricted neuropathology can be caused by this enzymopathy.
Insights
Neuropathic sphingomyelinase deficiency presents unique MRI findings in siblings, showing brain atrophy despite varied clinical symptoms. This suggests a restricted neuropathology in this rare genetic disorder.
Area of Science:
- Genetics
- Neurology
- Biochemistry
Background:
- Neuropathic sphingomyelinase deficiency is a rare genetic disorder.
- It is caused by mutations in the acid sphingomyelinase gene.
- Understanding its clinical and pathological spectrum is crucial for diagnosis and management.
Observation:
- Two siblings with identical mixed heterozygosity in the acid sphingomyelinase gene were studied.
- Both siblings presented with a protracted clinical course, reaching the fourth decade.
- MRI revealed pronounced cerebellar and mild supratentorial atrophy in both.
Findings:
- Despite similar MRI findings, the siblings exhibited strikingly different clinical statuses.
- One sibling had no overt neurological deficit, while the other showed neocerebellar symptoms, nystagmus, and cranial nerve palsies.
- Evidence of neuronal and Schwann cell storage was confirmed histopathologically and ultrastructurally.
Implications:
- This case series highlights a remarkably restricted neuropathology in neuropathic sphingomyelinase deficiency.
- The findings underscore the variability of clinical presentation despite a common genetic defect.
- Further research is needed to elucidate the genotype-phenotype correlations in this enzymopathy.