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

Abnormal Result

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.

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.

Although not strictly a patient case, I will discuss the applicability of 3D printing in the laboratory in two particular problems which presented itself in our laboratory.

Case 1

It so happened that a patient pulled the two electrodes of our iontophoresis machine with a forceful jerk, which caused the thin copper cables inside the insulating holder as shown below (cut open afterwards) to sever. See red and black cables below.

A spare cable was fortunately available from Tygerberg Hospital at the time to continue testing patients.

The damage to this cable made the iontophoresis machine unusable. Upon enquiry from the manufacturer, the cable was replaceable but would cost 320 euro (~ZAR5500) and would take weeks to order from Europe. At this bizarre price I reverted to try fix this cable for our laboratory (at least for a spare one should the new one be damaged in the future).

A multimeter was used to test which wires have been damaged and it turned out that 3 of the 4 connecting wires were broken.

Upon removing the thin insulating layers of the wires, the break in the connections were identified and the cables which I had available (recycled from old non-functioning ear phones) were used to solder in place on the connecting electronic chip board. See picture below.

The connecting electronic chip, shown above still needed proper isolation, and since I do have a 3D printer at home, I fairly quickly designed a small isolating box in which the chip would fit.

This was printed with PLA (polylactic acid – a biodegradeable plastic most often used in 3D printing) and the chip was Isolated and the box sealed with a hot glue gun and a soldering iron.

Case 2

While developing a method for Vitamin A measurement on the HPLC, during sample extraction, a batch of samples need to be dried on the Nitrogen Gas dryer. It so happened that the tubes which we used (high volume tubes) did not fit the current heating blocks used.

Our scientist requested I print a set of tube holder blocks to fit the holder for the nitrogen drying gas.

The holes in the aluminium heating blocks could also be drilled bigger and deeper to fit the tubes but that would make them unusable for another application with smaller tubes.

See below:

Apart from 3D printing a new button for our toasted in the communal kitchen, 3D printing 60-well reaction plates for Tissue Immunology etc, I’m often requested by certain people in the lab to print a certain part which is otherwise unobtainable in a reasonable time / at a reasonable cost.

HOSP #	MRN86510387	WARD	Internal medicine
CONSULTANT	Dr Jody Rusch	DOB/AGE	35 year female

Abnormal Result

Hypernatremia (sodium = 161 mmol/L)

Persistent Hypokalemia (potassium 1.9 mmol/L)

Presenting Complaint

Acute on chronic gastroenteritis

History

• 35 year old female. Known HIV positive on ARV with weight loss. GIT symptoms. To exclude villous atrophy/parasitic infestation.
• This is an HIV positive patient (CD4: 40 cells/uL; viral load: 54 869 copies/mL (4.74 log copies/ml))
• The patient has had a CD4 < 150 since 2018.
• HIV Viral load has never been suppressed <1000 copies / ml.
• There are concerns of ARV compliance

Examination

Not available

Laboratory Investigations

Two days earlier:

Test	Result
Sodium mmol/L	145
Potassium mmol/L	2.0 L
Chloride mmol/L	124 H
Urea mmol/L	7.9 H
Creatinine umol/L	246 H

Other Investigations

Histological examination requested after colonoscopy: Mild erythema of caecum. To exclude TB/CMV

Patient has undergone a colonoscopy as well as an enteroscopy and mild erythema of the caecum was seen.

The terminal ileum showed: intestinal metaplasia with preserved villous architecture. There is no evidence of active inflammation, ulceration or increased intraepithelial lymphocytes seen. There is no evidence of ova, viral inclusions, granulomas or parasites, and no evidence of dysplasia or malignancy present, hence no pathologic diagnosis.

The caecum biopsy, which was macroscopically erythematous, showed fragments of colonic mucosa with areas of crypt branching and focal gland associated neutrophils.

Final Diagnosis

Mild chronic active colitis.

Take Home Message

This patient, who has laboratory findings of AIDS, likely has a combination of aetiologies accounting for the deranged electrolytes. The acquired immune deficiency likely is complicated by repeated infections with accompanying inflammation of the colonic mucosa – this seems to have been ongoing for months already.

This may well likely have been causing dehydration which recently have caused acute kidney injury, with creatinine rising from a baseline of 86, three weeks prior, to ~250 umol/L.

Some simple bedside laboratory tests may be helpful in aetiological evaluation. In cases where diarrhea has persisted for more than two weeks, testing the stool for glucose and pH can be helpful in identifying those patients with severe villous atrophy. This can be done easily at the bedside with a urine dipstick if available. Glucose test tape, nitrazine paper, and Clinitest tablets also have been used. A stool glucose of greater than 2+ or a pH of less than 5.0 suggests substantial villous atrophy.