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Survival of a Male Infant with a Familial Xp11.4 Deletion Causing Ornithine Transcarbamylase Deficiency.

ABSTRACT: Ornithine transcarbamylase (OTC) deficiency is well known to cause severe neonatal hyperammonemia in males with absent enzyme activity. In families with large deletions of the X chromosome involving OTC and other contiguous genes, male infants appear to have an even more severe course. Notably, there are no published reports of these males surviving to liver transplant, even in cases where the diagnosis was known or suspected at birth. We describe two male newborns and their mother who all have a 1.5-Mb deletion of Xp11.4 encompassing the genes TSPAN7, OTC, and part of RPGR. The first child succumbed to his illness on his fourth day of life. His younger brother was diagnosed prenatally, and with early aggressive treatment, he survived the neonatal period. He suffered multiple life-threatening complications but stabilized and received a liver transplant at 7 months of age. This report demonstrates both the possibility of survival and the complications in caring for these patients.

SUBMITTER: McPheron M

PROVIDER: S-EPMC6336553 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Survival of a Male Infant with a Familial Xp11.4 Deletion Causing Ornithine Transcarbamylase Deficiency.

McPheron Molly M Lah Melissa M

JIMD reports 20181108

Ornithine transcarbamylase (OTC) deficiency is well known to cause severe neonatal hyperammonemia in males with absent enzyme activity. In families with large deletions of the X chromosome involving OTC and other contiguous genes, male infants appear to have an even more severe course. Notably, there are no published reports of these males surviving to liver transplant, even in cases where the diagnosis was known or suspected at birth. We describe two male newborns and their mother who all have ...[more]

PMID: 30406504

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Contiguous Xp11.4 Gene Deletion Leading to Ornithine Transcarbamylase Deficiency Detected by High-density Single-nucleotide Array.

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Hemizygous deletion in the <i>OTC</i> gene results in ornithine transcarbamylase deficiency: A case report.

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Complex management of a patient with a contiguous Xp11.4 gene deletion involving ornithine transcarbamylase: a role for detailed molecular analysis in complex presentations of classical diseases.

Project description:A male infant was diagnosed prenatally with a partial ornithine transcarbamylase (OTC) gene deletion and managed from birth. However, he displayed neurological abnormalities and developed pleural effusions, ascites and anasarca not solely explained by OTC deficiency (OTCD). Further evaluation of the gene locus using exon-specific PCR and high-density SNP array copy number analysis revealed a 3.9-Mb deletion from Xp11.4 to Xp21.1 including five additional gene deletions, three causing the known genetic diseases: Retinitis pigmentosa (RP3), X-linked chronic granulomatous disease (CGD) and McLeod syndrome. The case illustrates (1) the complexities of managing a patient with neonatal onset OTCD, CGD, RP3 and McLeod syndrome, (2) the need for detailed evaluation in seemingly "isolated" gene deletions and (3) the clinical utility of high-density copy number analysis for rapidly characterizing chromosomal lesions.

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Gene Mutation Analysis and Prenatal Diagnosis of the Ornithine Transcarbamylase (OTC) Gene in Two Families with Ornithine Transcarbamylase Deficiency.

Project description:BACKGROUND The aim of this study was to perform gene detection in 2 clinical cases of highly suspected ornithine transcarbamylase deficiency (OTCD) pediatric patients by first-generation sequencing technology in order to confirm the pathogenic genetic factors of their families and allow the families to undergo genetic counselling and prenatal diagnosis. MATERIAL AND METHODS The peripheral DNA samples of 2 children with highly suspected OTCD (the probands) and their parents were collected. DNA fragments corresponding to exons 1-10 of the OTC gene from the samples were amplified using polymerase chain reaction (PCR), and then subjected to Sanger sequencing to confirm the pathogenic mutation sites. RESULTS The probands were both confirmed to have OTCD. The proband in Family 1 was a male carrying a c.867+1G>C mutation at a splice site within the OTC gene. The gene detection results of amniotic fluid cells at 16 weeks of pregnancy showed that the fetus was a male who also carried the c.867+1G>C mutation. The proband in Family 2 was a male carrying a c.782T>C(p. I261T) mutation in the OTC gene. The gene detection results of amniotic fluid cells at 18 weeks showed that the fetus was a male without pathogenic mutations in the OTC gene. The gene detection results of peripheral blood from the fetus after birth were consistent with those obtained from amniotic fluid cells. CONCLUSIONS Pediatric children who are clinically suspected of OTCD can receive a definitive diagnosis through OTC gene detection.

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