Sulfite oxidase deficiency – An unusual late and mild presentation

Abstract

Introduction: Sulfite oxidase deficiency (SOD) is an autosomal recessive inherited disease usually presenting in the neonatal period with severe neurological symptoms including seizures, often refractory to anticonvulsant therapy, and a rapidly progressive encephalopathy resembling neonatal hypoxic ischemia, with premature death. Most patients develop dislocated ocular lenses. Later or milder presentations of SOD are being reported with increasing frequency. These presentations include neurological regression with loss of previously acquired milestones or movement disorders. Case report: We report a four years old girl presenting with intermittent ataxia and uncoordinated limb movements. A similar episode of ataxia had occurred previously, one year before, with complete neurologic recovery and normal developmental milestones. Bilateral lens dislocation had been recently diagnosed. Cranial MRI demonstrated bilateral globus pallidus enhancement. Low homocysteine was found in plasma and Sulfitest R was positive. Further investigations led to confirmation of isolated sulfite oxidase deficiency with no enzyme activity detected on skin fibroblasts culture. Discussion: This case illustrates the clinical variability of SOD and it is not only atypical but also seems to be the mildest form described so far. The association of ectopia lentis with a movement disorder, even without psychomotor regression, should prompt us to look for this diagnosis.

Homeostatic impact of sulfite and hydrogen sulfide on cysteine catabolism

“…Both hypotheses suggest that iSOD might cause a reduction in H 2 S levels, and therefore, some aspects of the disease symptoms may be associated with reduced H 2 S production. The SQR‐dependent thiosulfate production may gain further importance in iSOD when considering the reduced plasma cystine levels in iSOD patients (Touati et al, ; Rocha et al, ), since cysteine/cystine levels regulate GSH homeostasis (Yu and Long, ). With a K M for sulfite similar to SO (Jackson et al, ), a reduction in its primary substrate GSH would likely cause a switch from the production of persulfidated GSH to the production of thiosulfate (Figure ), which further supports the view of a depletion of H 2 S in iSOD/MoCD.…”

“…An alternative scenario could also explain high thiosulfate levels: the low concentration of cystine in iSOD patients (Touati et al, ; Rocha et al, ) may trigger an up‐regulation of the transsulfuration pathway via CSE (Yu and Long, ; Paul et al, ), which is an important factor in H 2 S biosynthesis. As a result, high H 2 S levels would contribute to increased thiosulfate production under sulfite excess.…”

Isolated Sulfite Oxidase Deficiency: Response to Dietary Treatment in a Patient with Severe Neonatal Presentation

“…Late onset cases often lack the more characteristic features like neonatal onset seizures. Atypical presentations have included metabolic stroke 8 and a movement disorder with ectopia lentis and regression 11 .…”

Whole Exome Sequencing Identified Novel Mutation in SUOX Gene Causes Extremely Rare Autosomal Recessive Isolated Sulfite Oxidase Deficiency

“…The patients with ISOD usually manifested with either fatal early-onset form presented with seizures, severe psychomotor retardation and death or late-onset form with comparatively milder clinical symptoms [8,9]. Genotype-phenotype relationship is quite clear, as type of mutation and residual sul te oxidase activity is directly correlated with the disease severity [10].…”

“…ISOD patient's laboratory test were majorly identi ed with positive urinary sul te test, i.e. (i) increased level of S-sulfocysteine, taurine, and thiosulfate with normal level of uric acid in urine, (ii) high level of Ssulfocysteine and taurine, normal level of uric acid and methionine and low level of cystine and homocysteine in plasma [8]. Patients with ISOD harbouring homozygous or compound heterozygous mutation in SUOX gene were identi ed with complete loss of sul te oxidase activity while asymptomatic carrier individual with heterozygous mutations in SUOX gene were usually presented with 50% loss of sul te oxidase activity [11,12].…”