Table 10.

Acute Inpatient Treatment in Individuals with Early-Onset Neonatal Dihydrolipoamide Dehydrogenase Deficiency

Manifestation/ConcernTreatmentConsideration/Other
Underlying precipitating factors Any precipitating factors (infection, fasting, medications) should be treated/discontinued as soon as possible.
Metabolic acidosis
  • For severe metabolic acidosis (pH <7.20) or if bicarbonate is ≤14 mEq/L, initiate bicarbonate therapy.
  • A common formula for bicarbonate dose: bicarbonate (mEq) = 0.5 x weight (kg) x [desired bicarbonate - measured bicarbonate]
  • Administer 1/2 of calculated dose as slow bolus & remaining 1/2 over 24 hrs.
  • Metabolic acidosis usually improves w/generous fluid & calorie support. 1
  • Bicarbonate therapy needed for severe metabolic acidosis 2
Promotion of an anabolic state D10 (half or full-normal saline) w/age-appropriate electrolytes should be started at maintenance rate & adjusted based on presence or absence of ↑ intracranial pressure or hypoglycemia.
  • Maintain glucose concentration in normal range.
  • Intralipids can be added to provide addl calories w/cautious monitoring for acidemia.
Correction of ↑ leucine concentration 3, 4
  • Withhold protein initially for a maximum of 24 hrs to avoid worsening of catabolism.
  • Then gradually reintroduce protein.
BCAAs should be introduced slowly & followed closely w/frequent plasma amino acid evaluations; see also MSUD.
Consider renal replacement therapies in clinical settings w/appropriate resources & expertise.When hemodialysis is used it must be coupled w/effective nutritional mgmt to constrain the catabolic response & prevent recurrent clinical intoxication. 5
Total protein intake (enteral + parenteral): 2-3.5 g/kg/day as BCAA-free amino acidsFor persons of any age who can tolerate enteral feeding (even if intubated), continuous nasogastric delivery (30-60 mL/hr) of a BCAA-free formula (0.7-1.2 kcal/mL) supplemented w/1% liquid solutions of isoleucine & valine can meet protein goals while providing addl calories.
Isoleucine & valine supplements (enteral + parenteral): 20-120 mg/kg/day each; titrate to plasma concentrations of 400-800 µmol/LFor parenteral administration, isoleucine & valine are each prepared as separate 1% solutions in normal saline.
Maintain serum osmolality w/in normal reference range (i.e., 275-300 mOsm/kg H2O). 6 Establish euvolemia using isotonic sodium chloride solutions.Overhydration & quickly infused boluses of fluids should be avoided if possible.
Measure serum osmolality & electrolytes every 6-12 hrs.Prevent serum osmolality from decreasing >5 mOsm/kg H2O per day (0.20 mOsm/kg H2O per hr).
Hypoglycemia
  • Start IV fluid.
  • Maintain blood glucose >100 mg/dL. 7
  • High-dose glucose needed to avoid catabolism
  • If there is hyperglycemia, start insulin infusion rather than ↓ glucose infusion rate.
Hyperammonemia
  • Hyperammonemia improves w/reversal of catabolism.
  • A high-dose glucose infusion w/insulin infusion is helpful in achieving this goal.
  • If severe hyperammonemia & altered mental status persist after above measures, extracorporeal toxin removal procedures such as hemodialysis & hemofiltration should be considered.
Although IV sodium benzoate + sodium phenylacetate have been used in such circumstances, their utility in DLD deficiency is doubtful, as most hyperammonemia is accompanied/caused by liver dysfunction, which is responsible for metabolism of nitrogen scavenger medications as well.
Carnitine deficiency Levocarnitine (IV or PO) 50-100 mg/kg/day divided three times per day should be given during the acute period.
Lactic acidosis DCA can be considered & continued.
  • If lactate decreases with its introduction
  • Polyneuropathy is a concern w/long-term use.
Seizures Standardized treatment w/ASM by experienced neurologist
  • Many ASMs may be effective; none has been demonstrated effective specifically for this disorder.
  • As seizures typically occur during acute decompensations, ASM may be discontinued when metabolic control is achieved.

ASM = anti-seizure medication; BCAAs = branched-chain amino acids; DCA = dichloroacetate; IV = intravenous; MSUD = maple syrup urine disease; PO = orally

1.

Although dextrose infusions may theoretically cause further lactate elevations during acute episodes, provision of dextrose-containing IV fluids is essential for the majority of acutely decompensated individuals. Only one affected individual experienced worsening acidosis with increased dextrose concentrations in the TPN.

2.

Note that bicarbonate therapy alone is not sufficient to correct the metabolic acidosis. Correction of metabolic acidosis relies on reversing the catabolic state by providing calorie support from glucose and interlipids.

3.
4.

If there is no evidence of hyperleucinosis, total protein intake can be at the recommended dietary allowance (RDA).

5.

Dialysis without simultaneous management of the underlying disturbance of protein turnover is analogous to treating diabetic ketoacidosis with invasive removal of glucose and ketones rather than insulin infusion. In both conditions, effective treatment depends not only on lowering concentrations of pathologic metabolites, but also on controlling the underlying metabolic derangement.

6.

To help avoid increased intracranial pressure

7.

If provision of dextrose-containing fluids worsens metabolic acidosis, consider decreasing the infusion rate and providing the majority of calories in the form of intralipid.

From: Dihydrolipoamide Dehydrogenase Deficiency

Cover of GeneReviews®
GeneReviews® [Internet].
Adam MP, Feldman J, Mirzaa GM, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-2024.
Copyright © 1993-2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.