Sulfite Oxidase Deficiency and Molybdenum Cofactor Deficiency Clinical Presentation

Updated: Feb 18, 2019
  • Author: Reena Jethva, MD; Chief Editor: Luis O Rohena, MD, PhD, FAAP, FACMG  more...
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Pregnancy and delivery history are typically normal, although numerous infants with sulfite oxidase deficiency have had depressed Apgar scores.

The "classic presentation" of sulfite oxidase deficiency includes intractable seizures in the first days or weeks of life and abnormal tone (particularly opisthotonos). Feeding difficulties are common shortly after birth. Poor growth may ensue. Affected individuals are at risk for severe psychomotor retardation, spasticity, and/or hypotonia. Most individuals have profound intellectual disability. Strokelike episodes (”metabolic stroke”) have been reported in cases of isolated sulfite oxidase deficiency.

Later or milder presentations of sulfite oxidase deficiency are being reported with increasing frequency. These presentations include neurologic regression with loss of previously acquired milestones or movement disorders. A review of 22 cases of isolated sulfite oxidase deficiency noted that age of onset was after the first month of life in 9 cases (10 weeks to 15 months) and that the oldest onset cases were more likely to have mild or no developmental delays; in some cases, movement or tone abnormalities were presenting symptoms instead of seizures. [2]

Other reported systemic issues include renal stones and ocular abnormalities such as lens dislocation. Hypertrophic cardiomyopathy was reported in a patient with molybdenum cofactor deficiency. [5]



Birth weight, height, and head circumference are usually normal in individuals with sulfite oxidase deficiency. Progressive microcephaly is commonly described to develop in infancy.

Neurologic examination may note the following [7] :

  • Axial hypotonia with peripheral hypertonia
  • Intractable tonic/clonic seizures
  • Myoclonus
  • Opisthotonos
  • Movement disorder
  • Hyperekplexia

The following characteristic craniofacial anomalies may be observed (see the image below):

Pictured is an infant with sulfite oxidase deficie Pictured is an infant with sulfite oxidase deficiency. Note the narrow bifrontal diameter and deep-set eyes.

See the list below:

  • Narrow bifrontal diameter
  • Frontal bossing
  • Depressed nasal bridge
  • Deep-set eyes
  • Full cheeks

The following ocular abnormalities are also common:

  • Dislocated lenses (may develop after the neonatal period)
  • Lack of response to light


Both isolated sulfite oxidase deficiency [8] and molybdenum cofactor deficiency are autosomal-recessive disorders. Two complementation groups are involved in molybdenum cofactor synthesis.

When sulfite oxidase is deficient, alternate metabolic pathways for sulfite are augmented, including formation of the metabolites S-sulfocysteine and thiosulfate. S-sulfocysteine probably substitutes for cysteine in connective tissues, which appears to weaken the zonule of the lens (a tissue normally rich in cysteine) and to result in the characteristic dislocated lenses. The pathogenesis of brain damage in individuals with sulfite oxidase deficiency is unknown but may be related to sulfite accumulation or lack of sulfate in the CNS. Animal studies have found that elevated sulfite levels have neurotoxic effects in rats.



Neurologic complications of sulfite oxidase deficiency include poor seizure control, spasticity, and profound intellectual disabilities. Other systemic complications include abnormal respiratory drive, poor feeding that requires a gastrostomy tube, vomiting, gastroesophageal reflux, and aspiration pneumonia.