A scoring system predicting the clinical course of CLPB defect based on the foetal and neonatal presentation of 31 patients

Research output: Contribution to journalJournal articleResearchpeer-review

  • Ewa Pronicka
  • Mariola Ropacka-Lesiak
  • Joanna Trubicka
  • Magdalena Pajdowska
  • Markus Linke
  • Østergaard, Elsebet
  • Carol Saunders
  • Sandra Horsch
  • Clara van Karnebeek
  • Joy Yaplito-Lee
  • Felix Distelmaier
  • Katrin Õunap
  • Shamima Rahman
  • Martin Castelle
  • John Kelleher
  • Safa Baris
  • Katarzyna Iwanicka-Pronicka
  • Colin G Steward
  • Elżbieta Ciara
  • Saskia B Wortmann
  • Additional individual contributors

Recently, CLPB deficiency has been shown to cause a genetic syndrome with cataracts, neutropenia, and 3-methylglutaconic aciduria. Surprisingly, the neurological presentation ranges from completely unaffected to patients with virtual absence of development. Muscular hypo- and hypertonia, movement disorder and progressive brain atrophy are frequently reported. We present the foetal, peri- and neonatal features of 31 patients, of which five are previously unreported, using a newly developed clinical severity scoring system rating the clinical, metabolic, imaging and other findings weighted by the age of onset. Our data are illustrated by foetal and neonatal videos. The patients were classified as having a mild (n = 4), moderate (n = 13) or severe (n = 14) disease phenotype. The most striking feature of the severe subtype was the neonatal absence of voluntary movements in combination with ventilator dependency and hyperexcitability. The foetal and neonatal presentation mirrored the course of disease with respect to survival (current median age 17.5 years in the mild group, median age of death 35 days in the severe group), severity and age of onset of all findings evaluated. CLPB deficiency should be considered in neonates with absence of voluntary movements, respiratory insufficiency and swallowing problems, especially if associated with 3-methylglutaconic aciduria, neutropenia and cataracts. Being an important differential diagnosis of hyperekplexia (exaggerated startle responses), we advise performing urinary organic acid analysis, blood cell counts and ophthalmological examination in these patients. The neonatal presentation of CLPB deficiency predicts the course of disease in later life, which is extremely important for counselling.

Original languageEnglish
JournalJournal of Inherited Metabolic Disease
Issue number6
Pages (from-to)853-860
Number of pages8
Publication statusPublished - Nov 2017

    Research areas

  • Journal Article

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