Infantile Refsum's disease: a generalized peroxisomal disorder. Case report with postmortem examination
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Infantile Refsum's disease (IRD) is a peroxisomal disorder. Autopsy findings in an IRD patient revealed specific liver, adrenal, and brain changes, differentiating it from related Zellweger syndrome and neonatal adrenoleukodystrophy.
Area of Science:
- Neurology
- Genetics
- Pathology
Background:
- Infantile Refsum's disease (IRD) is a peroxisomal deficiency disorder.
- Its distinction from neonatal adrenoleukodystrophy (NALD) and Zellweger syndrome (ZS) requires further clarification.
- This study presents the first autopsy report of a clinically and biochemically diagnosed IRD patient.
Observation:
- The patient exhibited micronodular liver cirrhosis, hypoplastic adrenals, and lipid macrophages in the liver, lymph nodes, and brain.
- Cerebral findings included cerebellar granule layer hypoplasia and ectopic Purkinje cells, with mild axonal and myelin reduction.
- Severe retinal and cochlear degenerative changes were noted, while peripheral nerves, skeletal system, and kidneys were normal.
Findings:
- Electron microscopy revealed characteristic bilamellar inclusions in macrophages and other cells, distinct from ZS and NALD.
- The IRD case lacked the active demyelination, cerebral cortical malformations, and adrenal degenerative changes seen in NALD.
- Key differences were observed in liver, adrenal, and central nervous system pathology compared to ZS and NALD.
Implications:
- This autopsy report provides crucial pathological data for understanding IRD.
- Distinguishing IRD from NALD and ZS is essential for accurate diagnosis and management.
- Further autopsy studies are needed to confirm these findings as consistent features of IRD.
Abstract:
Infantile Refsum's disease (IRD) is a peroxisomal deficiency disease which is closely related to neonatal adrenoleukodystrophy (NALD) and the Zellweger syndrome (ZS). Recent observations suggest that NALD and ZS are separate genetic disorders but the delimitation towards IRD remains uncertain. We present here the first autopsy report of a patient who was clinically and biochemically diagnosed as having IRD, and we compare the findings with those from NALD and ZS. The main gross and microscopic findings comprised micronodular liver cirrhosis, small hypoplastic adrenals without degenerative changes, and large groups of lipid macrophages in liver, lymph nodes and certain areas of the cerebral white matter. The brain showed no malformations except for a severe hypoplasia of the cerebellar granule layer and ectopic location of the Purkinje cells in the molecular layer. A mild and diffuse reduction of axons and myelin was found in the corpus callosum and periventricular white matter, the corticospinal tracts, and the optic nerves. Large numbers of perivascular macrophages were present in the same areas but there was no active demyelination. The retina and cochlea showed severe degenerative changes. Peripheral nerves, skeletal system and kidneys were normal. Electron microscopy showed characteristic cytoplasmic inclusions with bilamellar profiles in macrophages in the liver, lymph nodes and brain but not in the adrenals. Similar inclusions were found in liver cells and astrocytes. The findings differ from ZS which shows cortical renal cysts, skeletal changes, liver changes, cerebral micropolygyria, neuronal heterotopias, and demyelination of the white matter. Cases with NALD show mild cerebral malformations, active demyelination, degenerative changes of the adrenals, liver changes, and bilamellar electromicroscopic inclusions in macrophages. Our cases thus resembled NALD but lacked active demyelination, cerebral cortical malformations and adrenal degenerative changes. Further autopsy studies will be necessary to determine whether these changes are consistent findings in IRD.