Endocrine Abstracts

Sulfite oxidase deficiency encephalopathy is a rare genetic disease, secondary to the mutation of the SUOX gene, which codes for the enzyme sulfite oxidase that catalyzes the oxidation of sulfite to sulfate, an essential process for the catabolism of sulfur amino acids. This rare disease is characterized clinically by seizures, progressive encephalopathy and lens dislocation. The objectives of this report are to describe the clinical, paraclinical and evolutionary characteristics of this pathology, as well as the interest of prenatal and pre-implantation diagnosis in its management. This case involved a first-degree relative referred to the medical genetics department because of a personal history of 3 neonatal deaths in their offspring, at d6, d5 and d21 of life respectively, in a picture of epileptic encephalopathy appearing 12 hours after birth. The 3 pregnancies were well followed, carried to term, without any notion of acute fetal suffering, infectious syndrome or toxic intake. The newborns had normal birth weight and Apgar score, and no malformative or dysmorphic signs. A brain MRI could be performed in the last child and showed a T2 hypersignal of the supratentorial white matter, an arachnoid cyst of the posterior cerebral fossa, and hypoplasia of the cerebellum. Since no genetic analysis could be performed in the 3 newborns, and in view of the clinical and paraclinical picture suggesting an inborn metabolic disorder and the notion of 1st degree consanguinity, a high-speed sequencing of the exome of both parents was requested. A missense mutation NM_000456.2:c.1187A>G p.(Gln396Arg) of unknown significance (class 3) in the SUOX gene was found in the heterozygous state in both parents. In addition, a pathogenic missense mutation (class 1) of the TTC21B gene was found incidentally in the heterozygous state in the father. This mutation is responsible for hereditary nephronophthisis in the homozygous state. Given the family history and the results of genetic tests, the diagnosis of encephalopathy by sulfite oxidase deficiency by homozygous mutation of the SUOX gene was retained. This rare genetic disease, of unknown prevalence, is transmitted by autosomal recessive mode. Thus, the risk of recurrence for this couple is 25%. This explains the interest of genetic counselling, in order to propose a prenatal or pre-implantation diagnosis to the couple, and a search for the mutation in relatives at risk.

Keywords: encephalopathy by sulfite oxidase deficiency, SUOX gene, prenatal diagnosis, pre-implantation diagnosis.