Matthias Gautschi1, Christian Weisstanner2, Johannes Slotboom2, Esmeralda Nava3, Theres Zürcher3, Jean-Marc Nuoffer1. 1. 1] Department of Paediatrics, University Hospital Bern, Inselspital, Bern, Switzerland [2] Institute of Clinical Chemistry, University Hospital Bern, Inselspital, Bern, Switzerland. 2. Institute of Neuroradiology, University Hospital Bern, Inselspital, Bern, Switzerland. 3. Department of Paediatrics, University Hospital Bern, Inselspital, Bern, Switzerland.
Abstract
BACKGROUND: Multiple acyl-CoA dehydrogenase deficiency- (MADD-), also called glutaric aciduria type 2, associated leukodystrophy may be severe and progressive despite conventional treatment with protein- and fat-restricted diet, carnitine, riboflavin, and coenzyme Q10. Administration of ketone bodies was described as a promising adjunct, but has only been documented once. METHODS: We describe a Portuguese boy of consanguineous parents who developed progressive muscle weakness at 2.5 y of age, followed by severe metabolic decompensation with hypoglycaemia and coma triggered by a viral infection. Magnetic resonance (MR) imaging showed diffuse leukodystrophy. MADD was diagnosed by biochemical and molecular analyses. Clinical deterioration continued despite conventional treatment. Enteral sodium D,L-3-hydroxybutyrate (NaHB) was progressively introduced and maintained at 600 mg/kg BW/d (≈ 3% caloric need). Follow up was 3 y and included regular clinical examinations, biochemical studies, and imaging. RESULTS: During follow up, the initial GMFC-MLD (motor function classification system, 0 = normal, 6 = maximum impairment) level of 5-6 gradually improved to 1 after 5 mo. Social functioning and quality of life recovered remarkably. We found considerable improvement of MR imaging and spectroscopy during follow up, with a certain lag behind clinical recovery. There was some persistent residual developmental delay. CONCLUSION: NaHB is a highly effective and safe treatment that needs further controlled studies.
BACKGROUND:Multiple acyl-CoA dehydrogenase deficiency- (MADD-), also called glutaric aciduria type 2, associated leukodystrophy may be severe and progressive despite conventional treatment with protein- and fat-restricted diet, carnitine, riboflavin, and coenzyme Q10. Administration of ketone bodies was described as a promising adjunct, but has only been documented once. METHODS: We describe a Portuguese boy of consanguineous parents who developed progressive muscle weakness at 2.5 y of age, followed by severe metabolic decompensation with hypoglycaemia and coma triggered by a viral infection. Magnetic resonance (MR) imaging showed diffuse leukodystrophy. MADD was diagnosed by biochemical and molecular analyses. Clinical deterioration continued despite conventional treatment. Enteral sodium D,L-3-hydroxybutyrate (NaHB) was progressively introduced and maintained at 600 mg/kg BW/d (≈ 3% caloric need). Follow up was 3 y and included regular clinical examinations, biochemical studies, and imaging. RESULTS: During follow up, the initial GMFC-MLD (motor function classification system, 0 = normal, 6 = maximum impairment) level of 5-6 gradually improved to 1 after 5 mo. Social functioning and quality of life recovered remarkably. We found considerable improvement of MR imaging and spectroscopy during follow up, with a certain lag behind clinical recovery. There was some persistent residual developmental delay. CONCLUSION:NaHB is a highly effective and safe treatment that needs further controlled studies.
Authors: Nina N Stolwijk; Mirjam Langeveld; Bart A W Jacobs; Liffert Vogt; Jorien A Haverkamp; Sacha Ferdinandusse; Carla E M Hollak Journal: JIMD Rep Date: 2022-06-25
Authors: Willemijn J van Rijt; Emmalie A Jager; Derk P Allersma; A Çiğdem Aktuğlu Zeybek; Kaustuv Bhattacharya; François-Guillaume Debray; Carolyn J Ellaway; Matthias Gautschi; Michael T Geraghty; David Gil-Ortega; Austin A Larson; Francesca Moore; Eva Morava; Andrew A Morris; Kimihiko Oishi; Manuel Schiff; Sabine Scholl-Bürgi; Michel C Tchan; Jerry Vockley; Peter Witters; Saskia B Wortmann; Francjan van Spronsen; Johan L K Van Hove; Terry G J Derks Journal: Genet Med Date: 2020-01-06 Impact factor: 8.822