Dimethylglycine Dehydrogenase Deficiency in Siblings with Skeletal and Neurodevelopmental Manifestations
Biochemical/Metabolic and Therapeutics
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Primary Categories:
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Secondary Categories:
Introduction
Dimethylglycine dehydrogenase deficiency is a very rare inborn error of metabolism first described in 1999. The initial description of the condition involved an adult patient with a history of fishy body odor and unusual muscle fatigue with increased serum creatine kinase. A second case, described in 2017, involved an 11-month-old boy who presented with pneumonia and was found to have persistently increased serum creatine kinase, without fishy odor.
Case Presentation
In this case report, we describe a female proband who has skeletal manifestations including bilateral developmental hip dysplasia, intoeing gait, genu valgum, spondylolisthesis, mild scoliosis, as well as learning difficulties and autism spectrum disorder.
Diagnostic Workup
Extensive genetic testing did not identify a clear cause for her symptoms. Exome analysis revealed she is homozygous for a pathogenic variant in the DMGDH gene (c.2048dup, p.Leu684Alafs*13), without any other cause for her manifestations identified. Dosage of dimethylglycine in urine was significantly elevated, corroborating a diagnosis of dimethylglycine dehydrogenase deficiency. Screening of the proband’s siblings confirmed that her twin brother, who presents with language difficulties including dyspraxia, oppositional defiant disorder, attention deficit hyperactivity disorder, anxiety and a past medical history of mild developmental hip dysplasia, is also homozygous for the familial DMGDH variant. Her younger brother, who is not known for any physical or developmental abnormalities, was found to be a heterozygous carrier.
Discussion
This family represents the third published report of DMGDH deficiency, with a presentation that differs from the previously described individuals and includes skeletal and neurodevelopmental manifestations; the literature is currently too limited to determine if these features could be secondary to DMGDH deficiency. The previously reported “fishy body odor” was not present to date in this family, perhaps this feature appears with age.
Conclusion
This case report contributes to the limited literature on DMGDH deficiency and expands the phenotype potentially associated with this condition.
Dimethylglycine dehydrogenase deficiency is a very rare inborn error of metabolism first described in 1999. The initial description of the condition involved an adult patient with a history of fishy body odor and unusual muscle fatigue with increased serum creatine kinase. A second case, described in 2017, involved an 11-month-old boy who presented with pneumonia and was found to have persistently increased serum creatine kinase, without fishy odor.
Case Presentation
In this case report, we describe a female proband who has skeletal manifestations including bilateral developmental hip dysplasia, intoeing gait, genu valgum, spondylolisthesis, mild scoliosis, as well as learning difficulties and autism spectrum disorder.
Diagnostic Workup
Extensive genetic testing did not identify a clear cause for her symptoms. Exome analysis revealed she is homozygous for a pathogenic variant in the DMGDH gene (c.2048dup, p.Leu684Alafs*13), without any other cause for her manifestations identified. Dosage of dimethylglycine in urine was significantly elevated, corroborating a diagnosis of dimethylglycine dehydrogenase deficiency. Screening of the proband’s siblings confirmed that her twin brother, who presents with language difficulties including dyspraxia, oppositional defiant disorder, attention deficit hyperactivity disorder, anxiety and a past medical history of mild developmental hip dysplasia, is also homozygous for the familial DMGDH variant. Her younger brother, who is not known for any physical or developmental abnormalities, was found to be a heterozygous carrier.
Discussion
This family represents the third published report of DMGDH deficiency, with a presentation that differs from the previously described individuals and includes skeletal and neurodevelopmental manifestations; the literature is currently too limited to determine if these features could be secondary to DMGDH deficiency. The previously reported “fishy body odor” was not present to date in this family, perhaps this feature appears with age.
Conclusion
This case report contributes to the limited literature on DMGDH deficiency and expands the phenotype potentially associated with this condition.