Lipoyltransferase 1 Gene Defect Resulting in Fatal Lactic Acidosis in Two Siblings

Table 1

Laboratory evaluation of the proband.

Testing	Test	Results
Genetic tests	Chromosomal microarray analysis	High resolution identified a copy number gain of chromosome band 14q24.3 spanning approximately 0.255 Mb in a nondisease associated region. This gain contains at least five genes and is expected to be inherited 93% of the time. Parental studies were not recommended.
	CPT1A gene sequencing	No known deleterious mutations
	Comprehensive mitochondrial DNA analysis	No large deletions or deleterious mutations
	PC gene sequencing (pyruvate carboxylase deficiency)	No known deleterious mutations
	DLAT gene sequencing (pyruvate dehydrogenase E2 deficiency)	No known deleterious mutations
Biochemical analyses	Mitochondrial respiratory chain enzyme analysis, skin fibroblasts	Deficiencies in mitochondrial electron transport chain enzymes not detected
	Newborn screen	Pattern of elevation consistent with CPT1, otherwise normal
	Plasma amino acids	Suggestive of lactic acidemia, very elevated alanine, and serum glycine was normal
	Pyruvic acid	Elevated
	Urine organic acids	Notable for lactic aciduria, elevated 2-OH and 2-oxoacids

CPT1A/CPT1: carnitine palmitoyltransferase 1A.
PC: pyruvate carboxylase.
DLAT: dihydrolipoamide S-acetyltransferase.