Investigation of molybdenum cofactor deficiency due to MOCS2 deficiency in a newborn baby

Abstract

BackgroundMolybdenum cofactor deficiency (MOCD) is a severe autosomal recessive neonatal metabolic disease that causes seizures and death or severe brain damage. Symptoms, signs and cerebral images can resemble those attributed to intrapartum hypoxia. In humans, molybdenum cofactor (MOCO) has been found to participate in four metabolic reactions: aldehyde dehydrogenase (or oxidase), xanthine oxidoreductase (or oxidase) and sulfite oxidase, and some of the components of molybdenum cofactor synthesis participate in amidoxime reductase. A newborn girl developed refractory seizures, opisthotonus, exaggerated startle reflexes and vomiting on the second day of life. Treatment included intravenous fluid, glucose supplementation, empiric antibiotic therapy and anticonvulsant medication. Her encephalopathy progressed, and she was given palliative care and died aged 1 week. There were no dysmorphic features, including ectopia lentis but ultrasonography revealed a thin corpus callosum.ObjectivesThe aim of this study is to provide etiology, prognosis and genetic counseling.MethodsBiochemical analysis of urine, blood, Sanger sequencing of leukocyte DNA, and analysis of the effect of the mutation on protein expression.ResultsUric acid level was low in blood, and S-sulfo-L-cysteine and xanthine were elevated in urine. Compound Z was detected in urine. Two MOCS2 gene mutations were identified: c.501 + 2delT, which disrupts a conserved splice site sequence, and c.419C > T (pS140F). Protein expression studies confirmed that the p.S140F substitution was pathogenic. The parents were shown to be heterozygous carriers.ConclusionsMutation analysis confirmed that the MOCD in this family could not be treated with cPMP infusion, and enabled prenatal diagnosis and termination of a subsequent affected pregnancy.

Molybdenum cofactor and isolated sulphite oxidase deficiencies: Clinical and molecular spectrum among Egyptian patients

“…Seizure onset ranged from day 2 to day 50 of life, and a single case had a late onset at the age of 1 year which is considered to be rare in comparison with other more common neonatal MoCD onset. 8,17 The initial symptom of all our patients was seizures, which was reported to be the most common presenting symptom in both disorders. 18,19 …”

“…2,17 These entities are clinically similar, but normal xanthine, hypoxanthine, and uric acid levels are seen in SOD. 30,31 Our findings demonstrated increased S-sulphocysteine in all patients.…”

Molybdenum cofactor and isolated sulphite oxidase deficiencies: Clinical and molecular spectrum among Egyptian patients

“…Seizure onset ranged from day 2 to day 50 of life, and a single case had a late onset at the age of 1 year which is considered to be rare in comparison with other more common neonatal MoCD onset. 8,17 The initial symptom of all our patients was seizures, which was reported to be the most common presenting symptom in both disorders. 18,19 All the patients had accompanying severe developmental delay, and 7 had failure to thrive, which is in accordance with previous observations.…”

Diffic ulties of diagnostics of epilepsy due to mol ybdenum cofactor deficienc y: a case report

“…The results showed a homozygotic mutation on the exon 6 of MOCS2 gene, leading to deletion of amino acid in position 158 of the protein, which was described before in patients with molybdenum cofactor deficiency (OMIM: 252160). Дефицит кофактора молибдена является тяжелым наследственным аутосомно-рецессивным неонатальным метаболическим заболеванием, которое вызывает рефрактерные к терапии эпилептические приступы, черепные дизморфии, выраженное нервно-психическое недоразвитие и зачастую приводит к ранней смерти [1,4]. Клинические симптомы и данные нейровизуализации могут напоминать признаки, характерные для гипоксически-ишемической энцефалопатии новорожденных, что нередко приводит к диагностическим ошибкам [6,7].…”

“…У людей кофактор молибдена необходим для нормальной работы 3 ферментов: сульфитоксидазы, ксантиноксидазы (или ксантиндегидрогеназы, ксантиноксидоредуктазы) и альдегидоксидазы (или альдегиддегидрогеназы). Кроме того, некоторые из компонентов синтеза кофактора молибдена нужны для функционирования амидоксимедуктазы [1]. Аномальное накопление в мозге сульфита из-за потери активности сульфитоксидазы приводит к эксайтотоксическому повреждению нейронов [8].…”