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

• DOI: 10.1007/s10545-017-0057-z
• Publication Date: 2017-07-07T08:48:20Z
• Authors: Ewa Pronicka; Mariola Ropacka‐L...; Joanna Trubicka; Magdalena Pajdowska; Markus Linke; Elsebet Ostergaard; Carol Saunders; Sandra Horsch; Clara van Karnebeek; Joy Yaplito‐Lee; Felix Distelmaier; Katrin Õunap; Shamima Rahman; Martin Castelle; John Kelleher; Safa Baris; Katarzyna Iwanick...; Colin G. Steward; Elżbieta Ciara; Saskia B. Wortmann
• Keywords: DISORDER; Adult; Male; 0301 basic medicine; 3-METHYLGLUTACONIC ACIDURIA; Neutropenia; Adolescent; 610; Prenatal movement disorder; PROTEIN DISAGGREGATION; Cataract; 3-methylglutaconic Aciduria ; Cataracts ; Hyperekplexia ; Neutropenia ; Prenatal Movement Disorder ; Prenatal Seizures; Young Adult; 03 medical and health sciences; CATARACT; Fetus; Journal Article; Humans; Child; Brain Diseases; Movement Disorders; MUTATIONS; Cataracts; Infant, Newborn; Infant; Endopeptidase Clp; 3. Good health; CONGENITAL NEUTROPENIA; Hyperekplexia; Phenotype; Child, Preschool; Prenatal seizures; Female; 3-methylglutaconic aciduria; Atrophy; Metabolism, Inborn Errors

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