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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.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.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.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.

Objective To describe the clinical, biochemical and molecular genetic findings in Egyptian children with Molybdenum Cofactor and isolated sulfite oxidase deficiencies, for the first time in Egypt. Methods Six Egyptian patients from different pedigrees with confirmed Molybdenum co Factor or isolated sulfite oxidase deficiencies were included in the study. All the patients were subjected to a thorough general and neurologic examination, expanded metabolic screen and urine organic acid profile, brain MRI and quantitation of S-sulphocysteine and xanthine in urine by LC-Ms/Ms and 5/6 patients had molecular analysis for MCOS1 gene. Results All six patients presented with intractable seizures immediately after birth. Microcephaly, severe neurodevelopmental delay, swallowing dysfuction, axial hypotonia, spastic quadriparesis, hyperekeplexia, characteristic craniofacial abnormalities as narrow bifrontal diameter and deeply seated eyes was present in all 6 patients. Extraneurologic manifestations in the form of hypertrophic cardiomyopathy, and xanthine stones was detected in one patient each, both suffering from MCO deficiency. two patients were diagnosed biochemicaly as isolated sulphite oxidase deficiency and four patients with molybdenum cofactor deficiency. MRI of all patients was characterized by multiple severe volume loss & subcortical cysts. The common mutation detected was MCOS1. Conclusion Molybdenum co factor and sulphite oxidase deficiencies are a diagnosable inborn errors of metabolism. Brain MRI is crucial in pointing to the diagnosis by the presence of multiple cortical cysts simulating hypoxic cystic encephalomalacia.

Objective To study the prevalence of inherited metabolic disorders diagnosed at the Unit of inherited metabolic disease at Cairo University Children Hospital (CUCH), focusing on the wide variability of clinical presentations of these diseases as well as on the risk factors and demographic distribution. Methods 1289 patients were evaluated clinically at the neurometabolic unit from 2008 to 2010 with retrospective analysis of the data. Results Out of 1289 patients, 120 Patients were diagnosed as Phenylketonuria: 67 males (55.8%) and 53 females (44.2%), with age of presentation range (few days to 14 years). The remaining 1169 patients: 672 males (57.5%) with age range (1 week–18 years). Positive consanguinity was observed in 60.3% of patients. Excluding the PKU group: neurological manifestations were predominantly reported as 34.2% of clinical findings, non neurologic manifestations as 16.9%, dysmorphic/skeletal abnormalities and isolated short stature: 12.5%. Positive risk factors: 11.1%. Dermatological manifestations: 5.1%, ocular/auditory defects: 4.8%, failure to thrive: 4.7%. Metabolic disturbances: 4.3%. Organomegaly: 3.4%. CNS anomalies and neuroimaging findings: 2.7% and an asymptomatic group: 0.2%. A final diagnosis was confirmed in 782/1289 patients (60.6%) among which 288 (36.8%) were metabolic disorders: Aminoacidopathies were diagnosed in 146 patients (18.7%), lysosomal storage disorders in 78 (10%), organic acidurias in 18 (2.3%), dyslipideamias in 10 (1.3%), other leukodystrophies in 10 (1.3%), mitochondrial disorders in 9 (1.2%), carbohydrate metabolic disorders in 8 (1%), peroxisomal disorders in 6 (0.8%), metal disorders in 3 (0.4%), urea cycle disorders in 3 (0.4%) and 1 (0.1%) had a congenital disorder of glycosylation. 494 patients (63.2%) had genetic and other non metabolic diseases. Conclusion Inherited inborn errors of metabolism and genetic non metabolic disorders are not uncommon in Egyptian population due to high rate of consanguinous marriages. Therefore, we recommend initiation of a national newborn screening program or at least, a selective screening for the high risk families for early diagnosis and future prevention of disabilities caused by these disorders.