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

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.

• Authors: Matthias Gautschi, Christian Weisstanner, Johannes Slotboom, Esmeralda Nava, Theres Zürcher, Jean-Marc Nuoffer
• Journal: Pediatric research (Pediatr Res) Vol. 77 Issue 1-1 Pg. 91-8 (Jan 2015) ISSN: 1530-0447 [Electronic] United States
• PMID: 25289702 (Publication Type: Case Reports, Journal Article)

Chemical References

• Dietary Fats
• Ketones
• Ubiquinone
• coenzyme Q10
• Carnitine
• Riboflavin

Topics

• Brain (pathology)
• Carnitine (chemistry)
• Child, Preschool
• Coma (complications)
• Consanguinity
• Dietary Fats
• Hereditary Central Nervous System Demyelinating Diseases (metabolism)
• Humans
• Hypoglycemia (complications)
• Ketones (metabolism)
• Magnetic Resonance Imaging
• Male
• Multiple Acyl Coenzyme A Dehydrogenase Deficiency (metabolism)
• Muscle Weakness (pathology)
• Riboflavin (chemistry)
• Treatment Outcome
• Ubiquinone (analogs & derivatives, chemistry)