Dear colleague,
I reviewed in the pediatric department the child Léo AILLEBOUST, born on 21/01/2023, for the results report.
As a reminder, I had met Léo during a first hospitalization for advice on Leigh syndrome. The first symptoms began around 3 months of age with the observation of hypotonia and nystagmus, followed by the appearance of myoclonic seizures around 5 months of age. During his hospitalization for assessment, a permanent hyperlactacidemia and symmetrical hyperintensities of the substantia nigra and spinothalamic tracts were evidenced.
Given this strong suspicion of mitochondrial disease, a trio WES analysis and mitochondrial DNA sequencing on blood and urine were performed.
These analyses revealed a homozygous nonsense variant (p.Arg45Ter) in the NDUFAF2 gene, confirming a diagnosis of isolated Complex I deficiency in Léo. This pathology is an autosomal recessive condition, for which both of Léo's parents are heterozygous carriers. The recurrence risk for each new pregnancy is 25%.

Regarding Léo's evolution:
The pathology is progressive, and Léo had to be re-hospitalized for recurrent vomiting. Urinary amino acid chromatography also revealed a renal tubulopathy. The neurological examination has also deteriorated with the appearance of choreic movements.
We discussed the often grim evolution of the pathology and began to discuss palliative care. A multidisciplinary consultation meeting will be organized.

In summary:
Molecular confirmation of isolated Complex I deficiency linked to a homozygous pathogenic variant in NDUFAF2.
I will see the family again in a post-announcement consultation in 2 weeks.
Sincerely,