Due To LAD Deficiency Congenital Infantile Lactic Acidosis

Also Known As:

Lactic Acidosis, Congenital Infantile, Due To LAD Deficiency; DLD Deficiency; Dihydrolipoamide Dehydrogenase Deficiency; Lipoamide Dehydrogenase Deficiency, Lactic Acidosis due to; Maple Syrup Urine Disease, Type III

Networked: 16 relevant articles (0 outcomes, 0 trials/studies)

Disease Context: Research Results

Nutritional and Metabolic Diseases: 15
- Metabolic Diseases: 10142
Nervous System Diseases: 14178
- Central Nervous System Diseases: 4213
  - Brain Diseases: 15694
    - Metabolic Brain Diseases: 215
      - Inborn Metabolic Brain Diseases: 2
        Maple Syrup Urine Disease: 712
        Due To LAD Deficiency Congenital Infantile Lactic Acidosis: 16
Congenital, Hereditary, and Neonatal Diseases and Abnormalities: 933
- Inborn Genetic Diseases: 11939
  - Inborn Errors Metabolism: 1162
    - Inborn Metabolic Brain Diseases: 2
      - Maple Syrup Urine Disease: 712
        Due To LAD Deficiency Congenital Infantile Lactic Acidosis: 16
    - Inborn Errors Amino Acid Metabolism: 1
      - Maple Syrup Urine Disease: 712
        Due To LAD Deficiency Congenital Infantile Lactic Acidosis: 16

Related Diseases

1.	Lactic Acidosis
2.	Argininosuccinic Aciduria
3.	Mitochondrial Diseases (Mitochondrial Disease)
4.	Citrullinemia
5.	Mitochondrial Myopathies (Mitochondrial Myopathy)

Experts

1.	Dionisi-Vici, Carlo: 2 articles (01/2022 - 09/2014)
2.	Adam-Vizi, Vera: 2 articles (10/2019 - 08/2011)
3.	Ambrus, Attila: 2 articles (10/2019 - 08/2011)
4.	Torocsik, Beata: 2 articles (10/2019 - 08/2011)
5.	Ribes, Antonia: 2 articles (07/2014 - 12/2010)
6.	Tort, Frederic: 2 articles (07/2014 - 12/2010)
7.	Elpeleg, Orly: 2 articles (04/2007 - 07/2006)
8.	Angeloni, Antonio: 1 article (01/2022)
9.	Cairoli, Sara: 1 article (01/2022)
10.	Carducci, Claudia: 1 article (01/2022)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Due To LAD Deficiency Congenital Infantile Lactic Acidosis:

1.	Dihydrolipoamide Dehydrogenase (Lipoamide Dehydrogenase)IBA 12/01/2010 - "Dihydrolipoamide dehydrogenase (DLD) deficiency in a Spanish patient with myopathic presentation due to a new mutation in the interface domain." 07/15/2006 - "We have diagnosed dihydrolipoamide dehydrogenase (DLD) deficiency in two male second cousins, who presented with markedly different clinical phenotypes. " 11/01/2001 - "Dihydrolipoamide dehydrogenase (DLD) deficiency is a rare cause of primary lactic acidosis in infancy. " 08/01/2011 - "We investigated pathogenic mutations relevant in dihydrolipoamide dehydrogenase (LADH; gene: Dld) deficiency, a severe human disease, to elucidate how they alter reactive oxygen species (ROS) generation and associated biophysical characteristics of LADH. " 10/24/2022 - "Dihydrolipoamide dehydrogenase (DLD) deficiency is a recessive mitochondrial disorder caused by depletion of DLD from α-ketoacid dehydrogenase complexes. "
2.	Pyruvic Acid (Pyruvate)IBA 10/24/2022 - "Caenorhabditis elegans animal models of DLD deficiency generated by graded feeding of dld-1(RNAi) revealed that full or partial reduction of DLD-1 expression recapitulated increased pyruvate levels typical of pyruvate dehydrogenase complex deficiency and significantly altered animal survival and health, with reductions in brood size, adult length, and neuromuscular function. " 01/01/2014 - "Dihydrolipoamide dehydrogenase deficiency, also known as maple syrup urine disease (MSUD) type III, is caused by the deficiency of the E3 subunit of branched chain alpha-ketoacid dehydrogenase (BCKDH), α-ketoglutarate dehydrogenase (αKGDH), and pyruvate dehydrogenase (PDH). " 06/01/2014 - "A 16month-old female child on antiepileptic drugs (valproate and topiramate) was suspected to have the inherited metabolic disorder, dihydrolipoamide dehydrogenase deficiency, based on clinical symptoms and metabolic profile showing hyperalaninemia, elevated branched-chain amino acids, and lactate-pyruvate ratio. "
3.	CitrullineIBA 02/01/2014 - "Elevated plasma citrulline: look for dihydrolipoamide dehydrogenase deficiency." 01/01/2014 - "Citrulline has recently been identified as an elevated dried blood spot (DBS) metabolite in symptomatic patients affected with DLD deficiency. " 01/01/2014 - "Newborn screening for dihydrolipoamide dehydrogenase deficiency: Citrulline as a useful analyte." 01/01/2014 - "We additionally recommend that DLD deficiency be included in the "citrullinemia/elevated citrulline" ACMG Act Sheet and Algorithm." 02/01/2014 - "In conclusion, we suggest that elevated plasma citrulline in the absence of urea cycle defects warrants an investigation for DLD deficiency. "
4.	Branched-Chain Amino AcidsIBA 12/01/2010 - "Despite differing degrees of clinical severity, all three had minimal clues to DLD deficiency, with occasional minor increases in α-ketoglutarate and branched-chain amino acids. " 11/01/2001 - "This article presents the results of biochemical and molecular analyses and metabolic response to treatment procedures in a 10-week old boy presenting with vomiting, progressive hypotonia, lactic acidosis (pH 7.04; BE - 20; B-lactate 6.6 mmol/l, controls <2.1; CSF-lactate 4.8 mmol/l, controls <2.0), increased levels of branched chain amino acids in blood, and increased urinary excretion of branched chain oxo-acids due to DLD deficiency. " 06/01/2014 - "A 16month-old female child on antiepileptic drugs (valproate and topiramate) was suspected to have the inherited metabolic disorder, dihydrolipoamide dehydrogenase deficiency, based on clinical symptoms and metabolic profile showing hyperalaninemia, elevated branched-chain amino acids, and lactate-pyruvate ratio. "
5.	Lactic Acid (Lactate)FDA LinkGeneric 11/01/2001 - "This article presents the results of biochemical and molecular analyses and metabolic response to treatment procedures in a 10-week old boy presenting with vomiting, progressive hypotonia, lactic acidosis (pH 7.04; BE - 20; B-lactate 6.6 mmol/l, controls <2.1; CSF-lactate 4.8 mmol/l, controls <2.0), increased levels of branched chain amino acids in blood, and increased urinary excretion of branched chain oxo-acids due to DLD deficiency. " 06/01/2014 - "A 16month-old female child on antiepileptic drugs (valproate and topiramate) was suspected to have the inherited metabolic disorder, dihydrolipoamide dehydrogenase deficiency, based on clinical symptoms and metabolic profile showing hyperalaninemia, elevated branched-chain amino acids, and lactate-pyruvate ratio. "
6.	Urea (Carbamide)FDA LinkGeneric 02/01/2014 - "The control group included 19 patients in whom urea cycle defects were ruled out but DLD deficiency was suspected. " 02/01/2014 - "In conclusion, we suggest that elevated plasma citrulline in the absence of urea cycle defects warrants an investigation for DLD deficiency. " 01/01/2022 - "Herein, we report ten subjects with positive NBS for a mild elevation of citrulline (<100 μmol/L), in whom molecular investigations revealed carriers status for argininosuccinate synthase deficiency, a milder form of argininosuccinate lyase deficiency and two other diseases, lysinuric protein intolerance and dihydrolipoamide dehydrogenase deficiency, not primarily affecting the urea cycle. "
7.	Oxidoreductases (Dehydrogenase)IBA 10/24/2022 - "Dihydrolipoamide dehydrogenase (DLD) deficiency is a recessive mitochondrial disorder caused by depletion of DLD from α-ketoacid dehydrogenase complexes. " 01/01/2014 - "Dihydrolipoamide dehydrogenase deficiency, also known as maple syrup urine disease (MSUD) type III, is caused by the deficiency of the E3 subunit of branched chain alpha-ketoacid dehydrogenase (BCKDH), α-ketoglutarate dehydrogenase (αKGDH), and pyruvate dehydrogenase (PDH). "
8.	EnzymesIBA 10/15/2019 - "Underlying molecular alterations in human dihydrolipoamide dehydrogenase deficiency revealed by structural analyses of disease-causing enzyme variants." 07/01/2014 - "As in DLD deficiency, a broader clinical spectrum can be anticipated for lipoate synthesis defects depending on which of the affected enzymes is most rate limiting. "
9.	Reactive Oxygen Species (Oxygen Radicals)IBA 08/01/2011 - "We investigated pathogenic mutations relevant in dihydrolipoamide dehydrogenase (LADH; gene: Dld) deficiency, a severe human disease, to elucidate how they alter reactive oxygen species (ROS) generation and associated biophysical characteristics of LADH. "
10.	Biomarkers (Surrogate Marker)IBA 02/01/2014 - "Since we observed elevated plasma citrulline levels in a number of confirmed cases, we retrospectively examined the value of citrulline as a biochemical marker for DLD deficiency. "

Therapies and Procedures

1.	Ketogenic Diet 10/07/2021 - "The Effects of a Ketogenic Diet on Patients with Dihydrolipoamide Dehydrogenase Deficiency."
2.	Therapeutics 04/10/2007 - "The latter could contribute to the metabolic derangement associated with DLD deficiency and represent a target for therapies of this condition."