Chronic Leigh Disease: a genetic and biochemical study

Area of Science:

• Genetics and Neurology
• Biochemistry

Background:

• Leigh disease is a rare, severe neurological disorder.
• Investigating the genetic and biochemical basis of adult-onset Leigh disease is crucial for understanding its inheritance patterns and clinical variability.

Observation:

• A large family with a history of Leigh disease was studied, including neurological and biochemical examinations of 68 individuals across seven generations.
• An adenosine triphosphate-thiamine diphosphate phosphoryltransferase inhibitor factor was detected in 20% of examined individuals, with 5 exhibiting neurological abnormalities.

Findings:

• The inhibitor factor was present in individuals with varying degrees of neurological deficits, from severe to subtle.
• Parental consanguinity was noted in affected family members, and the trait affected both males and females without vertical transmission.
• The study identified a chronic relapsing course in some patients, exacerbated by metabolic stress.

Implications:

• Multigenerational data suggest Leigh disease in adults follows an autosomal recessive inheritance pattern.
• The findings highlight variable expression and a wide spectrum of neurological manifestations in adult Leigh disease.
• Identifying the inhibitor factor may aid in diagnosing and understanding the pathogenesis of Leigh disease.