Isolated sulfite oxidase deficiency

Isolated sulfite oxidase deficiency (ISOD) is a life-threatening, autosomal recessive disease characterized by severe neurological impairment. As no long-term effective treatment is available, distinction from other treatable diseases, such as molybdenum cofactor deficiency (MoCD) type A, should be made. We reviewed 47 patients (45 previously reported in the literature). Cases were reviewed for consanguinity, sex, age at onset, death, clinical findings (including spasticity, seizures, psychomotor retardation, feeding difficulties, ectopia lentis, microcephaly), laboratory findings [urinary sulfite, S-sulfocysteine (in plasma and urine), plasma cystine, total homocysteine, uric acid, and oxypurines in urine] and radiological findings (including cerebral/cerebellar atrophy, cystic white matter changes, ventriculomegaly). We also aligned the published SUOX gene mutations to the reference sequence NM_000456.2. Onset occurred mostly during the first 72 h of life (57%) and within the first year of life in all but two patients (96%). All patients presented with neurological abnormalities, such as neonatal axial hypotonia and/or peripheral hypertonia (100%), (pharmacoresistant) seizures (84%), or developmental delay (97%). Feeding problems were also common. As found in our review, measurement of homocysteine in plasma, amino acids in plasma/urine, and sulfite in fresh urine supports the diagnosis of ISOD. Analysis of uric acid (plasma) and oxypurines (urine) is useful to rule out MoCD. In all patients in whom brain magnetic resonance imaging/computed tomography (MRI/CT) was performed, brain abnormalities were found. The purpose of this literature review is to provide a thorough overview of clinical, neuroimaging, biochemical, and genetic findings of patients with ISOD.