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

Matthew Edwards, Juliane Roeper, Catherine Allgood, Raymond Chin, Jose Angel Santamaria-Araujo, Flora Yuen-Wait Wong, Guenter Schwarz, John Whitehall

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Molybdenum 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. OBJECTIVES: The aim of this study is to provide etiology, prognosis and genetic counseling. METHODS: Biochemical analysis of urine, blood, Sanger sequencing of leukocyte DNA, and analysis of the effect of the mutation on protein expression. RESULTS: Uric 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. CONCLUSIONS: Mutation 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.
Original languageEnglish
Pages (from-to)43 - 49
Number of pages7
JournalMeta Gene
Volume3
DOIs
Publication statusPublished - 2015

Cite this

Edwards, M., Roeper, J., Allgood, C., Chin, R., Santamaria-Araujo, J. A., Wong, F. Y-W., ... Whitehall, J. (2015). Investigation of molybdenum cofactor deficiency due to MOCS2 deficiency in a newborn baby. Meta Gene, 3, 43 - 49. https://doi.org/10.1016/j.mgene.2014.12.003
Edwards, Matthew ; Roeper, Juliane ; Allgood, Catherine ; Chin, Raymond ; Santamaria-Araujo, Jose Angel ; Wong, Flora Yuen-Wait ; Schwarz, Guenter ; Whitehall, John. / Investigation of molybdenum cofactor deficiency due to MOCS2 deficiency in a newborn baby. In: Meta Gene. 2015 ; Vol. 3. pp. 43 - 49.
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abstract = "Molybdenum 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. OBJECTIVES: The aim of this study is to provide etiology, prognosis and genetic counseling. METHODS: Biochemical analysis of urine, blood, Sanger sequencing of leukocyte DNA, and analysis of the effect of the mutation on protein expression. RESULTS: Uric 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. CONCLUSIONS: Mutation 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.",
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language = "English",
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Edwards, M, Roeper, J, Allgood, C, Chin, R, Santamaria-Araujo, JA, Wong, FY-W, Schwarz, G & Whitehall, J 2015, 'Investigation of molybdenum cofactor deficiency due to MOCS2 deficiency in a newborn baby', Meta Gene, vol. 3, pp. 43 - 49. https://doi.org/10.1016/j.mgene.2014.12.003

Investigation of molybdenum cofactor deficiency due to MOCS2 deficiency in a newborn baby. / Edwards, Matthew; Roeper, Juliane; Allgood, Catherine; Chin, Raymond; Santamaria-Araujo, Jose Angel; Wong, Flora Yuen-Wait; Schwarz, Guenter; Whitehall, John.

In: Meta Gene, Vol. 3, 2015, p. 43 - 49.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Investigation of molybdenum cofactor deficiency due to MOCS2 deficiency in a newborn baby

AU - Edwards, Matthew

AU - Roeper, Juliane

AU - Allgood, Catherine

AU - Chin, Raymond

AU - Santamaria-Araujo, Jose Angel

AU - Wong, Flora Yuen-Wait

AU - Schwarz, Guenter

AU - Whitehall, John

PY - 2015

Y1 - 2015

N2 - Molybdenum 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. OBJECTIVES: The aim of this study is to provide etiology, prognosis and genetic counseling. METHODS: Biochemical analysis of urine, blood, Sanger sequencing of leukocyte DNA, and analysis of the effect of the mutation on protein expression. RESULTS: Uric 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. CONCLUSIONS: Mutation 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.

AB - Molybdenum 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. OBJECTIVES: The aim of this study is to provide etiology, prognosis and genetic counseling. METHODS: Biochemical analysis of urine, blood, Sanger sequencing of leukocyte DNA, and analysis of the effect of the mutation on protein expression. RESULTS: Uric 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. CONCLUSIONS: Mutation 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.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4329827/pdf/main.pdf

U2 - 10.1016/j.mgene.2014.12.003

DO - 10.1016/j.mgene.2014.12.003

M3 - Article

VL - 3

SP - 43

EP - 49

JO - Meta Gene

JF - Meta Gene

SN - 2214-5400

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