Human D-Lactate Dehydrogenase Deficiency: A Case Report in a Young Boy

Area of Science:

• Biochemistry
• Genetics
• Metabolic Disorders

Background:

• D-lactate is normally undetectable in circulation.
• Human D-lactate dehydrogenase deficiency (hDDLD) causes elevated plasma D-lactate and D-lactic acidosis.
• Neurological symptoms can be associated with hDDLD.

Purpose of the Study:

• To report a case of hDDLD in a Danish patient with delayed psychomotor development and metabolic acidosis.
• To identify the genetic cause of hDDLD using whole genome sequencing.
• To compare clinical and laboratory findings with existing literature.

Main Methods:

• Whole genome sequencing (WGS) to identify genetic variants.
• Metabolic screening of plasma and urine for D-lactate levels.
• Literature review comparing patient findings with other hDDLD cases.

Main Results:

• A homozygous deletion in the LDHD gene (NM_194436.3c: 1_930del, p.M1_Q310del) was identified.
• Elevated D-lactate levels were confirmed in plasma and urine.
• Clinical presentation included delayed psychomotor development and metabolic acidosis.

Conclusions:

• Pathogenic variants in the LDHD gene cause human D-lactate dehydrogenase deficiency.
• hDDLD exhibits broad phenotypic variability, ranging from neurological findings to elevated plasma urate.
• Consistent elevation of D-lactate in plasma and urine is a hallmark of hDDLD.