Table 9.

Routine Daily Treatment in Individuals with Early-Onset Neonatal Dihydrolipoamide Dehydrogenase Deficiency

Principle/ManifestationTreatmentConsideration/Other
Protein/BCAA restriction 1, 2, 3 Protein intake at RDA if no hyperleucinosis is present
If significant hyperleucinosis is present, consider providing protein that consists of 2-3 g/kg/day from BCAA-free amino acids.
  • Leucine tolerance for neonates: 65-85 mg/kg/day
  • Breast milk or regular infant formula can be used as a natural protein source.
  • Dried blood spots by overnight mail for monitoring of amino acid concentrations if available (See Surveillance.) 4
  • Leucine restriction should be maintained until hyperleucinosis resolves.
Defective carbohydrate oxidation Ketogenic/high-fat diet 5Of 7 persons treated:
  • 5 had no clinical benefit, & 2 of the 5 experienced ↑ in acidosis & hypoglycemia; 5
  • 2 improved clinically. 6
Inhibition of PDH kinase activity DCA supplementation (50-75 mg/kg/day)
  • 4 of 5 persons treated w/DCA in the literature experienced at least transient ↓s in lactic acid elevations.
  • Chronic use of DCA can result in polyneuropathy.
Poor weight gain /
Failure to thrive 		Feeding therapy; gastrostomy tube placement may be required for persistent feeding issues.Low threshold for clinical feeding eval &/or radiographic swallowing study when showing clinical signs or symptoms of dysphagia
Developmental delay /
Intellectual disability 		Standard treatment per developmental pediatrician / neurodevelopmental teamIncl PT, OT, & speech therapy as indicated
Cardiac dysfunction Standard treatment per cardiologist
Vision impairment /
Optic atrophy 		Standard treatment per ophthalmologist

BCAA = branched-chain amino acids; DCA = dichloroacetate; OT = occupational therapy; PDH = pyruvate dehydrogenase; PT = physical therapy; RDA = recommended dietary allowance

1.

Recommendations are based on decreased branched-chain α-ketoacid dehydrogenase (BCKDH) complex activity.

2.

Restriction of protein to recommended dietary allowances has been attempted with questionable results.

3.

Three of the six reported individuals experienced laboratory and/or clinical improvement with the use of protein restriction alone or in combination with medication therapy.

4.

For rapidly growing infants, monitoring weekly or twice weekly is recommended.

5.

Ketogenic/high-fat diets are frequently employed in individuals who have pyruvate dehydrogenase (PDH) complex deficiency [Patel et al 2012].

6.

One was treated with lipid infusions (instead of high-dextrose infusions) during acute episodes [Hong et al 1997, Cerna et al 2001].

From: Dihydrolipoamide Dehydrogenase Deficiency

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