NDUFS8-Related Leigh Syndrome Mimicking a Leukodystrophy

Area of Science:

• Neuroscience
• Genetics
• Mitochondrial Biology

Background:

• Leigh syndrome is a progressive infantile neurodegenerative disorder affecting mitochondrial metabolism.
• It is genetically heterogeneous, with various inheritance patterns.
• NDUFS8-related Leigh syndrome involves a nuclear gene encoding a mitochondrial complex I subunit.

Purpose of the Study:

• To present a case of Leigh syndrome with an unusual presentation of confluent white matter disease.
• To highlight a novel homozygous variant in the NDUFS8 gene.
• To emphasize the differential diagnosis of mitochondrial disorders in early childhood white matter disease.

Main Methods:

• Clinical case presentation of a 6-month-old girl.
• Initial neuroimaging suggestive of leukodystrophy.
• Genetic analysis revealing a novel homozygous variant in the NDUFS8 gene.

Main Results:

• The patient presented with clinical symptoms consistent with Leigh syndrome.
• Neuroimaging showed confluent white matter disease, atypical for classic Leigh syndrome.
• A novel homozygous variant in the NDUFS8 gene was identified as the likely cause.

Conclusions:

• Mitochondrial disorders, specifically NDUFS8-related Leigh syndrome, should be considered in the differential diagnosis of infantile confluent cerebral white matter disease.
• This case expands the phenotypic spectrum of NDUFS8-related disorders.
• Early consideration of mitochondrial dysfunction is crucial for accurate diagnosis and management.