DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY (DLDD)

Q: What is DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY (DLDD)?

very rare (<1:1000000) autosomal recessive mutation in the DLD gene antiepileptic drugs (valproate and topiramate) resulted in a profile that mimicked PDH (E3) [Mampilly GT et al. 2014]

Q: Gibt es eine deutsche Bezeichnung?

Dihydrolipoamid-Dehydrogenase-Mangel; Pyruvat-Dehydrogenase E3-Mangel

Q: Which enzymes are involved?

Dihydrolipoyl dehydrogenase, mitochondrial

Question 1

What is  DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY (DLDD)?

Accepted Answer

very rare (<1:1000000)
autosomal recessive
mutation in the DLD gene
antiepileptic drugs (valproate and topiramate) resulted in a profile that mimicked PDH (E3) [Mampilly GT et al. 2014]

Question 2

Gibt es eine deutsche Bezeichnung?

Accepted Answer

Dihydrolipoamid-Dehydrogenase-Mangel; Pyruvat-Dehydrogenase E3-Mangel

Question 3

What is the link to OMIM ?

Accepted Answer

OMIN 246900

Question 4

Which enzymes are involved?

Accepted Answer

Dihydrolipoyl dehydrogenase, mitochondrial

Disease	DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY (DLDD)
Synonym	DLD DEFICIENCY; E3 DEFICIENCY; MSUD TYPE III
OMIM	246900 OMIM = Online Mendelian Inheritance of Men
Orphanet	2394
Protein (UniProt)	Dihydrolipoyl dehydrogenase, mitochondrial
ExPASy	1.8.1.4
Gene locus	7q31.1
ICD	E74.4
Summary	very rare (<1:1000000) autosomal recessive mutation in the DLD gene antiepileptic drugs (valproate and topiramate) resulted in a profile that mimicked PDH (E3) [Mampilly GT et al. 2014]
Laboratory findings	2-Oxoadipic acid inc (urine) Citrulline inc (plasma) 2-Oxoglutaric acid inc (urine) L-Lactic acid inc (urine) Ammonia inc (blood) D-Glucose normal/dec (blood) L-Isoleucine inc (plasma) L-Lactic acid inc (blood) Lactate/Pyruvate ratio inc (blood) Leucine inc (plasma) Pyruvic acid inc (blood) Sedoheptulose-7-phosphate inc (urine) Valine inc (plasma)
Symptoms	hyperammonemia hypoglycemia lactic acidosis ataxia basal ganglia, changes, lesions, calcifications (MRI, CT) cardiomyopathy cardiomyopathy, hypertrophic cortical or cerebral atrophy developmental delay dystonia early death encephalopathy failure to thrive feeding difficulties, poor feeding growth retardation, poor growth hepatomegaly (large liver) intracerebral, cortical or paraventricular cysts Leigh syndrome liver failure liver involvement or dysfunction mental retardation metabolic acidosis microcephaly (<2 SD for age) motor retardation muscle weakness onset, infancy onset, neonatal Organic acids, urine seizures stridor tachypnea, hyperpnea, dyspnea, hyperventilation vomiting