High succinate in the urine

HOSP # WARD Paediatric OPD
CONSULTANT   Prof. George van der Watt DOB/AGE 3 months male

Abnormal Result

Figure 1 – Total Ion Chromatogram showing Increased succinate (@12.6 min) in the urine organic acid profile.

Presenting Complaint

3week old female.
Sample from Edendale lab.
No clinical info. No lab form available.

History

None available. Unfortunately this is often the case with specimens sent to the laboratory, even for something as complicated as an organic acid analysis.

Examination

None available.

Symptoms and signs of a serious disorder (SUCLA2) where succinate would be raised are:

  • early onset low muscle tone
  • severe muscular atrophy
  • scoliosis
  • movement disorders such as dystonia and hyperkinesia
  • epilepsy
  • growth retardation

Laboratory Investigations

Test Result
Lactate   2,1  mmol/L
TSH  6,92 H mIU/L (0.3-5.88)
Free T4  15,1   pmol/L (11.4-20.9)
Free T3   6,1  pmol/L (2.7 – 7.3)

Other Investigations

None known

Final Diagnosis

Bacterial degradation of urine most likely. Hippurate gets degraded to succinate by bacteria. Since there’s no hippurate present in the urine, this is the most likely explanation for this metabolic picture in the urine.

Take Home Message

Succinate is a metabolite very often seen in urine organic acid analyses.

If one sees very high succinate associated with moderate increase in methylmalonate then SUCLA2 must be excluded – a Leigh-like mitochondrial cytopathy.

Methylmalonate was absent in this child’s urine sample – it also increases in this condition.

Figure 2 – Total ion chromatogram of an unrelated case, showing the usual location of hippurate at 20.6 minutes.

Mutations in the SUCLA2 gene leading to SUCLA2 deficiency result in Leigh’s or a Leigh-like syndrome with onset of severe hypotonia, muscular atrophy, sensorineural hearing impairment, and often death in early childhood – hence it’s an important condideration, albeit not the aetiology in this child.

Another important fact about succinate is that fumarate (another Krebs cycle intermediate) is usually lower than succinate. Some authors have described that a reversed succinate:fumarate ratio (i.e. fumarate higher than succinate) indicates likely mitochondrial cytopathy. This should further be evaluated if no overt cause can be found.