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Updated: Mar 12, 2026
An In Vitro Model for the Study of Cellular Pathophysiology in Globoid Cell Leukodystrophy
Published on: October 21, 2014
[A Case of Pol III-related Leukodystrophy with Homozygous Mutation in POLR3A]
Tomoaki Shima1, Takeshi Fujimoto, Teiichiro Miyazaki
1Department of Neurology, Sasebo City General Hospital, Department of Neurology, Sasebo City General Hospital.
Abstract:
We describe a 27-year-old man with mental retardation, symptomatic epilepsy, myopia, and cerebellar ataxia without spontaneous puberty whose brain magnetic resonance imaging showed hypomyelination. He had child-like facial appearance, with thin facial hair. He had no underarm and pubic hairs, and his penis was small. Laboratory tests showed low levels of luteinizing hormone, follicle-stimulating hormone, and testosterone. Brain MRI showed diffuse hypomyelination, atrophy of the cerebellum and brainstem, and hypoplastic corpus callosum. Ictal N-isopropyl-p-(indone-123)-iodoamphetamine single photon emission computed tomography (123I-IMP SPECT) revealed hypoperfusion of bilateral frontal cingulate and temporal lobe and cerebellar hemispheres. Homozygous missense mutation c.2350G>A was found in POLR3A and the patient was diagnosed with Pol III-related leukodystrophy, which is a rare disease. We describe the present case in light of the characteristics of the past reports in Japan. (Received April 5, 2016: Accepted June 30, 2016; Published November 1, 2016).
Insights
This study details a rare case of Pol III-related leukodystrophy in a man with hypomyelination, epilepsy, and hypogonadism. Genetic analysis identified a POLR3A mutation, confirming the diagnosis of this rare neurological disorder.
Area of Science:
- Neurology
- Genetics
- Radiology
Background:
- Pol III-related leukodystrophy is a rare genetic disorder affecting brain white matter.
- It is characterized by hypomyelination and can present with various neurological and developmental issues.
Observation:
- A 27-year-old man presented with mental retardation, epilepsy, myopia, cerebellar ataxia, and absent puberty.
- Clinical examination revealed a child-like appearance, sparse facial and pubic hair, and small genitalia.
- Brain MRI showed diffuse hypomyelination, cerebellar and brainstem atrophy, and a hypoplastic corpus callosum.
- 123I-IMP SPECT imaging indicated hypoperfusion in frontal, temporal, and cerebellar regions.
Findings:
- Laboratory tests revealed low luteinizing hormone, follicle-stimulating hormone, and testosterone levels.
- Genetic testing identified a homozygous missense mutation (c.2350G>A) in the POLR3A gene.
- The patient was diagnosed with Pol III-related leukodystrophy.
Implications:
- This case expands the understanding of POLR3A mutations and their clinical manifestations.
- It highlights the importance of neuroimaging and genetic testing in diagnosing rare leukodystrophies.
- Further research into Pol III-related leukodystrophy can aid in developing targeted therapies.
