Abstract
Aim—Molybdenum cofactor deficiency (MoCD) and Sulfite oxidase deficiency (SOD) are rare
autosomal recessive conditions of sulfur-containing amino acid metabolism with overlapping
clinical features and emerging therapies. The clinical phenotype is indistinguishable and they can
only be differentiated biochemically. MOCS1, MOCS2, MOCS3, and GPRN genes contribute to
the synthesis of molybdenum cofactor, and SUOX gene encodes sulfite oxidase. The aim of this
study was to elucidate the clinical, radiological, biochemical and molecular findings in patients
with SOD and MoCD.
Methods—Detailed clinical and radiological assessment of 9 cases referred for neonatal
encephalopathy with hypotonia, microcephaly, and epilepsy led to a consideration of disorders of
sulfur-containing amino acid metabolism. The diagnosis of six with MoCD and three with SOD
was confirmed by biochemical tests, targeted sequencing, and whole exome sequencing where
suspicion of disease was lower.
Results—Novel SUOX mutations were detected in 3 SOD cases and a novel MOCS2 mutation in
1 MoCD case. Most patients presented in the first 3 months of life with intractable tonic–clonic
seizures, axial hypotonia, limb hypertonia, exaggerated startle response, feeding difficulties, and
progressive cystic encephalomalacia on brain imaging. A single patient with MoCD had
hypertrophic cardiomyopathy, hitherto unreported with these diseases.
Interpretation—Our results emphasize that intractable neonatal seizures, spasticity, and feeding
difficulties can be important early signs for these disorders. Progressive microcephaly, intellectual
disability and specific brain imaging findings in the first year were additional diagnostic aids.
These clinical cues can be used to minimize delays in diagnosis, especially since promising
treatments are emerging for MoCD type A.