Molybdenum cofactor deficiency and isolated sulfite oxidase deficiency
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A term newborn feeds poorly and develops intractable seizures on day 2. Glucose, ammonia, and lactate are normal, so the workup moves away from the usual metabolic causes. Brain MRI at the end of the first week shows diffuse cystic encephalomalacia resembling severe hypoxic-ischemic injury, though the delivery was uncomplicated. Serum uric acid is very low.
- Autosomal recessive
- Molybdenum cofactor deficiency: MOCS1 (type A, most common), MOCS2 (type B), GPHN (type C, gephyrin)
- Isolated sulfite oxidase deficiency: SUOX, a clinical phenocopy
- The cofactor is required by three enzymes: sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase. Nearly all the damage comes from losing sulfite oxidase, because sulfite accumulation is neurotoxic
- Intractable neonatal seizures, typically within the first days of life
- Severe encephalopathy, feeding difficulty, exaggerated startle
- Ectopia lentis (dislocated lens), usually appearing after the neonatal period
- Progressive microcephaly, spastic quadriparesis
- Brain MRI mimics severe hypoxic-ischemic encephalopathy, which is the usual misdiagnosis in a baby with no perinatal event to explain it
- Low or undetectable serum uric acid is the cheap screening clue, and it is often already on the chart. Xanthine dehydrogenase makes uric acid, so losing the cofactor removes the supply
- Fresh urine sulfite by dipstick, which must be tested on a fresh sample because sulfite oxidizes on standing and gives a false negative
- Elevated urine S-sulfocysteine, the more reliable confirmatory metabolite
- Low plasma total homocysteine (sulfite inhibits the transsulfuration pathway), a useful supporting clue
- Confirm with sequencing of MOCS1, MOCS2, GPHN, or SUOX
Separating the two
| Molybdenum cofactor deficiency | Isolated sulfite oxidase deficiency | |
|---|---|---|
| Urine sulfite, S-sulfocysteine | High | High |
| Serum uric acid | Low | Normal |
| Treatable | Type A only, with fosdenopterin | No specific therapy |
Uric acid is the single test that separates them, because sulfite oxidase deficiency leaves xanthine dehydrogenase intact.
- Fosdenopterin (cPMP) is approved for molybdenum cofactor deficiency type A and is effective only if started very early, before irreversible injury. This makes rapid recognition genuinely consequential rather than academic
- No specific therapy exists for type B, type C, or isolated sulfite oxidase deficiency; care is supportive with seizure management
- Dietary restriction of methionine and cysteine has been tried with limited benefit
- Prenatal diagnosis and immediate postnatal treatment for a subsequent affected pregnancy
- A newborn with intractable seizures, cystic brain injury, and no birth asphyxia should have a uric acid checked. It is a routine test that points straight at a diagnosis most workups miss.
- Molybdenum makes uric acid. No molybdenum cofactor, no uric acid. That one sentence carries both the mechanism and the test.
- Test urine sulfite on a fresh sample. A dipstick run on a sample that has been sitting is the classic false negative.
- Lens dislocation plus seizures also occurs in classical homocystinuria, but there homocysteine is high, whereas here it is low.