Highly efficient ketone body treatment in multiple acyl-CoA dehydrogenase deficiency-related leukodystrophy

作者：Gautschi Matthias^*; Weisstanner Christian; Slotboom Johannes; Nava Esmeralda; Zuercher Theres; Nuoffer Jean Marc

来源：Pediatric Research, 2015, 77(1): 91-98.

DOI：10.1038/pr.2014.154

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 (approximate to 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 (motorfunction 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.

• 出版日期2015-1