Stéphanie Paquay

Uncommon Leber “Plus” Disease Associated With Mitochondrial Mutation m.11778G>A in a Premature Child

Leber hereditary optic neuropathy is a well-known mitochondrial disorder that leads to bilateral subacute visual failure. Although visual impairment is often the sole clinical feature, additional and severe neurologic abnormalities also have been documented for this disease. We report on a 13-year-old boy who has presented with severe visual failure since early childhood in a context of prematurity. In the first years of his life, clinical features included delayed psychomotor development and ataxia. The clinical presentation, which was initially attributed to prematurity, worsened thereafter, and the child developed acute neurologic degradation with the typical radiological findings of Leigh syndrome. The mitochondrial DNA point mutation 11778G>A was identified in the ND4 gene. The probable influence of environmental background on clinical expression of Leber optic neuropathy, particularly those of prematurity and oxygen therapy, is discussed in our manuscript.

Transient neonatal renal failure and massive polyuria in MEGDEL syndrome

Background MEGDEL (3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome) syndrome is a mitochondrial disorder associated with recessive mutations in SERAC1. Objectives To report transient neonatal renal findings in MEGDEL syndrome. Results This 7 year-old girl was the first child of consanguineous Turkish parents. She exhibited an acute neonatal deterioration with severe lactic acidosis and liver failure. Initial evaluation revealed massive polyuria and renal failure with 3-methylglutaconic aciduria. Symptoms and biological findings progressively improved with symptomatic treatment but lactic acidosis and high lactate to pyruvate ratio along with 3-methylglutaconic aciduria persisted. At 8 months of age, a subacute neurological degradation occurred with severe hypotonia, dystonia with extrapyramidal movements and failure to thrive. Brain MRI revealed basal ganglia lesions suggestive of Leigh syndrome. At 3 years of age, sensorineural deafness was documented. MEGDEL syndrome was further confirmed by the identification of an already reported homozygous mutation in SERAC1. Conclusion Transient neonatal polyuria and renal failure have not been reported to date in SERAC1 defective patients. Such neonatal kidney findings expand the clinical spectrum of MEGDEL syndrome.