What does low Lactate Dehydrogenase (LDH) show?

Low Lactate Dehydrogenase (LDH): Clinical Significance and Interpretation

Low LDH levels are rare and typically not clinically significant, but may indicate hereditary LDH subunit deficiency, particularly of the H-subunit, which is characterized by reduced enzyme activity in both serum and red blood cells. 1, 2

Understanding LDH

LDH is an enzyme found in nearly all cells of the body, with high concentrations in:

• Heart
• Liver
• Muscles
• Kidneys
• Lungs
• Blood cells

Normal LDH values in adults typically range from 125-220 U/L (or IU/L) 3. LDH serves as an important marker of tissue damage or disease across multiple organ systems.

Clinical Significance of Low LDH

Low LDH levels are uncommon and rarely reported in clinical practice for several reasons:

• Most clinical guidelines focus on elevated LDH as a marker of disease 4, 3
• Low LDH is not typically associated with specific pathological conditions
• Hereditary deficiency of LDH subunits is rare

Hereditary LDH Deficiency

The most documented cause of low LDH is hereditary deficiency of LDH subunits:

• Autosomal recessive inheritance pattern 1
• Most commonly affects the H-subunit of LDH 1, 2
• Complete deficiency shows only LDH5 isozyme on electrophoresis 1
• Associated with:
  • Marked elevation of fructose-1,6-diphosphate (FDP)
  • Increased dihydroxyacetonephosphate (DHAP)
  • Elevated glyceraldehyde-3-phosphate (GA3P)
  • Potential hemolysis in some cases 1

Diagnostic Considerations

When low LDH is detected:

1. Confirm with repeat testing
2. Examine both serum and erythrocyte LDH isozyme patterns 2
3. Consider immunoblotting with anti-H subunit antibody for definitive diagnosis 2
4. Evaluate family history for potential hereditary pattern

Clinical Implications

Patients with LDH subunit deficiencies may face:

• Risk of misdiagnosis of other clinical conditions due to reduced LDH release 2
• Potential underestimation of tissue damage in conditions where LDH is used as a marker
• Possible hemolysis in some cases of complete H-subunit deficiency 1

Contrast with Elevated LDH

While low LDH has limited clinical significance, elevated LDH is an important marker for:

• Malignancies (hematologic and solid tumors) 4, 3
• Tissue damage and ischemia 3
• Hemolysis 3
• Various organ-specific disorders 3

Conclusion

Low LDH levels are uncommon and generally not associated with specific disease states except for rare hereditary enzyme deficiencies. The clinical focus is typically on elevated LDH as a marker of tissue damage, malignancy, and other pathological conditions.