Isolated sulfite oxidase deficiency: mutation analysis and DNA‐based prenatal diagnosis

Abstract

Isolated sulfite oxidase deficiency is an autosomal recessive, neurological disorder resulting from a defect in SUOX, the gene encoding the enzyme that catalyzes the terminal reaction in the sulfur amino acid degradation pathway. In its classical, severe form, sulfite oxidase deficiency leads to intractable seizures, severe and progressive brain pathology and death at an early age. We report here on clinical features and mutational analysis of the genetic defect in a newborn with sulfite oxidase deficiency. Cultured fibroblasts from this patient exhibited no detectable sulfite oxidase activity, and a unique four base pair deletion was present in the cDNA isolated from the same source. Identification of the same genetic defect in a heterozygous state in each of the parents and the monitoring of subsequent pregnancies in this family by DNA-based prenatal diagnosis are also described. The deletion mutation was identified in a homozygous state in uncultured chorionic villus tissue from the second pregnancy that was subsequently terminated. In the third pregnancy, the presence of sulfite oxidase activity and identification of the mutation in a heterozygous state suggested that the fetus was not affected. This pregnancy resulted in the birth of a normal child.

Isolated sulphite oxidase deficiency mimics the features of hypoxic ischaemic encephalopathy

“…Prenatal diagnosis may be carried out by assay of sulphite oxidase activity or DNA mutation analysis on uncultured chorionic villus samples collected at 11-14 weeks gestation. The use of DNA analysis is only possible if the index case has been previously characterised by those means [6,7]. These techniques avoid the delays inherent in enzyme analysis on cultured amniocytes, a method that has also been used in this condition [9].…”

Characterization of Chloride-Depleted Human Sulfite Oxidase by Electron Paramagnetic Resonance Spectroscopy: Experimental Evidence for the Role of Anions in Product Release

“…In humans SO is essential for normal neonatal neurological development, and inborn deficiencies in SO result in severe physical and neurological disorders and early death (2, 3). …”

Sulfite-oxidizing enzymes

“…These severe neurological symptoms result from either point mutations in the SO protein itself (so-called isolated SO deficiency, in which only SO activity is affected), or the inability to properly produce the pyranopterindithiolate cofactor, which results in deficiencies in all Mo-containing enzymes (so-called Mo cofactor deficiency) [10][11][12]. The development of methods to clone and express human SO has revealed several different clinical point mutations that result in isolated SO deficiency [13][14][15][16]. The X-ray structure of the human SO is not yet available, although the structure of the human SO heme domain was reported [17].…”