Introduction
Molybdenum cofactor deficiency type B (MOCODB, #252160) is an autosomal
recessive metabolic disorder characterized by intractable seizures of
neonatal-onset, muscular spasticity, accompanying with hypouricemia,
elevated urinary sulfite levels and craniofacial dysmorphism. It came to
medical attention first in 1980 (Johnson, 1980). Affected children show
severe neurologic complications, which may lead to early death, rarely
(only three cases described to date) presented with a milder form with
global developmental delay without seizures (Arican, 2019). The disorder
results from decreased activity of sulfite oxidase (SUOX; EC 1.8.3.1)
and xanthine dehydrogenase (XDH; EC 1.17.1.4 and 1.17.3.2), which are
molybdenum cofactor-dependent for their activity.
Molybdenum cofactor (MOSC2) is encoded by the MOCS2 gene,
localized on chromosome 5q11.2. Its biosynthesis is, however, a
multistep process, involving: synthesis of precursor Z by proteins
encoded by MOCS1 (603707), conversion of precursor Z to
molybdopterin (MPT) by MPT synthase (MOCS2), attachment of molybdenum to
the dithiolene moiety of MPT by gephyrin (GPHN; EC 2.10.1.1 and
2.7.7.75) (Reiss, 1999; Reiss and Hahnewald, 2011). MOCS2 is
bicistronic, overlapping open reading frames (ORFs) which encode MOCS2A
and MOCS2B, the two subunits of MPT synthase (Leimkuhler, 2003), what
implicates its functioning and molecular diagnostics of MOSC deficiency.
In this paper, we like to present another patient, in whom novel,
inframe variant within the MOCS2 gene was identified. We aim to
delineate the MOCS2 phenotype and give evidence of the clinical
significance of the novel variant.