[Clinical and genetic features of early-onset progressive encephalopathy associated with NAXE gene mutations]

Area of Science:

• Genetics
• Neurology
• Biochemistry

Background:

• Early-onset progressive encephalopathy is a rare, lethal neurological disorder.
• Mutations in the NAXE gene are identified as the cause.
• The NAXE gene is crucial for the mitochondrial NAD(P)HX repair system.

Purpose of the Study:

• To report the clinical and genetic characteristics of a patient with early-onset progressive encephalopathy.
• To highlight new compound heterozygous mutations in the NAXE gene.
• To emphasize the link between NAXE mutations and the NAD(P)HX repair system deficiency.

Main Methods:

• Clinical case study of a 4-year-old boy.
• Genetic analysis to identify NAXE gene mutations.
• Review of patient's symptoms and family history.

Main Results:

• The patient presented with progressive walking instability, limb weakness, strabismus, ataxia, hypotonia, developmental delay, and recurrent respiratory failure.
• New compound heterozygous mutations (c.255 A>T and c.361 G>A) in the NAXE gene were identified.
• The identified mutations impair the epimerase function essential for NADHX and NADPHX repair.

Conclusions:

• NAXE gene mutations lead to a deficiency in the mitochondrial NAD(P)HX repair system, causing early-onset progressive encephalopathy.
• The disease is characterized by rapid progression and a high risk of respiratory failure, particularly after infections.
• This case expands the understanding of NAXE-related disorders and their genetic basis.