Mild phenotype in Molybdenum cofactor deficiency: A new patient and review of the literature

Abstract

Background Molybdenum cofactor deficiency (MoCD) is a rare autosomal‐recessive disorder that results in the combined deficiency of molybdenum‐dependent enzymes. Four different genes are involved in Molybdenum cofactor biosynthesis: MOCS1, MOCS2, MOCS3, and GEPH. The classical form manifests in the neonatal period with severe encephalopathy, including intractable seizures, MRI changes that resemble hypoxic‐ischemic injury, microcephaly, and early death. To date, an atypical phenotype with late‐onset has been reported in the literature in 13 patients. Methods We describe a late‐onset and a relatively mild phenotype in a patient with MOCS2 homozygous mutation. Results Pyramidal and extrapyramidal signs are recognized in those patients, often exacerbated by intercurrent illness. Expressive language is usually compromised. Neurological deterioration is possible even in adulthood, probably due to accumulation of sulfite with time. Conclusion Sulfite inhibition of mitochondrial metabolism could be responsible for the ischemic lesions described in patients with MoCD or alternatively could predispose the brain to suffer an ischemic damage through the action of other insults, for instance intercurrent illness. It is possible that sulfite accumulation together with other external triggers, can lead to neurological deterioration even in adulthood. The role of other factors involved in clinical expression should be investigated to establish the reason for phenotypic variability in patients with the same mutation.

Proteins Structure Models in the Evaluation of Novel Variant (C.472_477del) in the MOCS2 Gene

“…It first came to medical attention in 1980 [ 1 ]. Affected children show severe neurologic complications, which may lead to early death, and rarely (only seven cases described to date) present with a milder form with global developmental delay without seizures [ 2 , 3 ]. The severe manifestation of the disease is characterized by neonatal-onset, intractable seizures, severe feeding difficulties, accompany by progressive neurological deterioration (opisthotonos, hypertonicity, spastic quadriplegia) and cystic leukomalacia in brain MR.…”

Genotype-Phenotype Dissociation in Two Taiwanese Children with Molybdenum Cofactor Deficiency Caused by MOCS2 Mutation

“…10 Recently published articles have reviewed MoCoD patients reported in the literature and delineated the phenotypic spectrum: a narrow phenotypic spectrum across patients in the early-onset form with severe neurological impairment and a pattern of global injury susceptibility of the forebrain and cerebellum may be driven mainly by genotype; a wider phenotypic spectrum in patients with the late-onset form ranged from static neurologic symptoms to progressive neurological involvement with periodic decompensation in function, even in adulthood, and the pattern of selective injury susceptibility of the basal ganglia and cerebellum may be driven by a complex interaction of genotype, external environment triggers, and developmental context. 5,8 In addition, the residual enzymatic activity of sulfite oxidase might contribute to the phenotypes. 5 One of the limitations of this study was the lack of available data on sulfite oxidase activity, so it was not possible to draw definitive conclusions from our results.…”

“…The neuroimaging features of the late-onset form could be isolated basal ganglia changes or similar to the early-onset form. 8 We herein describe two Taiwanese MoCoD patients who harbored the same MOCS2 genotypes and had diverse clinical neuroimaging features.…”

<p>Molybdenum Cofactor Deficiency: Mega Cisterna Magna in Two Consecutive Pregnancies and Review of the Literature</p>

“…14 A residual molybdenum cofactor enzymatic function can usually be found and all three MOCS genes had been involved in this variant. [12][13][14] Probably, there are other similar cases that have not been diagnosed due to their mild clinical symptoms that can be confused with other pathologies.…”