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Severe Neonatal Metabolic Decompensation in Methylmalonic Acidemia Caused by CblD Defect

  • R. PariniEmail author
  • F. Furlan
  • A. Brambilla
  • D. Codazzi
  • S. Vedovati
  • C. Corbetta
  • T. Fedeli
  • B. Merinero
  • B. Pérez
  • M. Ugarte
Part of the JIMD Reports book series (JIMD, volume 11)

Abstract

CblD disorder is an autosomal recessive, rare, heterogeneous disease with variable clinical presentations, depending on the nature and location of the MMADHC gene mutations. Mutations in MMADHC lead to three distinct phenotypes: cblD-MMA, cblD-HC, and cblD-MMA/HC. To date, 18 cblD patients have been reported. Six of them were affected by cblD-MMA, but only three had a known clinical history. One of these patients presented with a metabolic decompensation at 11 months; the second one, born prematurely, was diagnosed with cblD after being treated for intracranial hemorrhage, respiratory distress syndrome, necrotizing enterocolitis, and convulsions at birth; the third one was diagnosed at 5 years of age.

Here we present a case of a cblD-MMA patient who had an acute neonatal onset with severe hyperammonemia requiring hemodiafiltration. To the best of our knowledge, this is the first cblD-MMA patient who presented acutely in the newborn period. He has developed well upon treatment with B12, carnitine, and hypoproteic diet. At present time, at the age of 7, he shows normal growth and cognitive development. Thus, it is likely that the aggressive treatment of this child with hemodiafiltration might have prevented him from long-term neurological sequelae. Overall, this case shows that even severe, neonatal-onset patients may display a vitamin B12-responsive MMA. Furthermore, it suggests that an early treatment with vitamins might be beneficial for patients presenting with neonatal-onset hyperammonemia regardless of the suspected disease and before receiving the biochemical diagnosis.

Keywords

Sodium Benzoate Megaloblastic Anemia Orotic Acid Metabolic Decompensation Methylmalonic Aciduria 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

Ado-Cbl

Adenosylcobalamin

Cbl

Cobalamin

HC

Homocystinuria

Met-Cbl

Methylcobalamin

MLS

Mitochondrial leader sequence

MMA

Methylmalonic aciduria

MMADHC

Methylmalonic aciduria cblD type with homocystinuria gene

Notes

Acknowledgments

We acknowledge Fondazione Pierfranco e Luisa Mariani, Milano, for their generous support to our clinical activities and Dr. Marcello Arsura, American Business English School, Novara, Italy, for the English editing of the text.

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • R. Parini
    • 1
    Email author
  • F. Furlan
    • 1
  • A. Brambilla
    • 1
  • D. Codazzi
    • 2
  • S. Vedovati
    • 2
  • C. Corbetta
    • 3
  • T. Fedeli
    • 1
  • B. Merinero
    • 4
  • B. Pérez
    • 4
  • M. Ugarte
    • 4
  1. 1.Rare Metabolic Diseases Unit and Neonatal Intensive Care Unit, Fondazione MBBMA.O. San GerardoMonzaItaly
  2. 2.Pediatric Intensive Care UnitA.O. Ospedali Riuniti di BergamoBergamoItaly
  3. 3.Laboratory for Neonatal Screening and Metabolic DiseasesOspedale Buzzi, A.O. Istituti Clinici di PerfezionamentoMilanItaly
  4. 4.CEDEM, CBM-SO, CIBERERUniversidad Autónoma MadridMadridSpain

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