Diagnostic

Diagnostic Services

Inborn errors of metabolism (IEMs) are a group of rare, inherited diseases that result from abnormalities in the body’s ability to break down nutrients from food or to synthesise certain essential molecules. At the NMP we use various sophisticated techniques and instrumentation in the diagnostic processes of identification of various metabolites associated with IEMs. 

Symptomatic presentation of IEMs are very unpredictable and in some cases non-specific. They can occur at any time from infancy to adulthood. Timely emergency intervention and treatment are paramount in improving the quality of life in these patients.

The work of our highly skilled Metabolomics team has led to major advances in our understanding of how genetic defects can lead to diseases and how to better treat those diseases.

Selective Lysosomal disorder screening (PLSD)
DRIED BLOOD SPOT

Glycosaminoglycan (GAGs/MPS, Total and individual GAG assessment) URINE

Thin layer chromatography of mono-/oligosaccharides (qualitative)
URINE

Quantitative Organic Acids (Includes orotic acid, includes succinylacetone on request)
URINE

Quantitative Very Long Chain Fatty Acids, Phytanic acid, Pristanic acid
SERUM

Pipecolic acid
SERUM

Quantitative Acylcarnitines URINE

Quantitative Acylcarnitines SERUM

Quantitative Acylcarnitines DRIED BLOOD SPOT

Quantitative Amino Acids URINE

Quantitative Amino Acids SERUM

Quantitative Amino Acids DRIED BLOOD SPOT

Quantitative Phenylalanine
DRIED BLOOD SPOT

Quantitative Glycine Specific Assay
CSF + SERUM

Intact glycoprotein (transferrin) analysis to screen for congenital disorders of glycosylation (CDG)
SERUM

Trimethylaminuria (TMAU): Quantitative TMA (trimethylamine) and FMO3 gene sequencing
URINE + EDTA BLOOD

Biotinidase Enzyme Activity Determination
DRIED BLOOD SPOT

Quantitative Galactose-1-Phosphate
DRIED BLOOD SPOT

Mitochondrial respiratory chain enzyme analyses (NHLS)
MUSCLE

Immunoreactive trypsinogen (IRT) neonates <24 days
DRIED BLOOD SPOT

Mitochondrial respiratory chain enzyme analyses (PRIVATE)
MUSCLE

Galactose-1-phosphate uridyltransferase (GALT) Enzyme Activity
DRIED BLOOD SPOT

Full Metabolic Evaluation
URINE

Full Metabolic Evaluation URINE

Selective Lysosomal disorder screening (PLSD) DRIED BLOOD SPOT

Description

Quantitative enzyme activity analysis of acid beta-glucosidase (GBA), acid alpha-glucosidase (GAA), Sphingomyelinase (SMPD1), alpha-galactosidase (GLA), galactocerebrosidase (GALC), alpha-L-iduronidase (IDUA). The test also include the following reflex international testing based on the following clinical criteria that must be provided:
1. Gaucher disease suspected and Gaucher/ASMD is selected on the request form: International referral for lyso-GL1/Gb1 testing.
2. Mucopolysaccharidosis suspected and MPS panel is selected on the request form: International referral for expanded mucopolysaccharidosis testing including MPS II, IIIb, IVa, VI and VII.
3. Fabry disease suspected in a female patient and Fabry disease is selected on the request form: International referral for Biomarker Lyso-GL3/Gb3 testing.
4. International referral for genetic testing if enzyme activity testing is suggestive of Gaucher, Niemann-Pick A/B, Pompe, Fabry or MPS I, II, IIIb, IVa, VI or VII. Krabbe disease is not included.
5. International referral lyso-GL1/Gb1, -GL3/Gb3 and -ASM measurement for monitoring of patients previously diagnosed with Gaucher, Fabry and Niemann-Pick A/B respectively.

Please note that selecting all options or none on the DBS-card will result in NO reflex testing

Comments

The 6-Plex-test and associated reflex referrals can be used for the diagnosis of the following defects:
– Gaucher-, Niemann-Pick A/B-, Pompe-, Fabry- and Krabbe-disease.
– MPS I (Hurler-Scheie), II (Hunter), IIIb (Sanfilippo), IVa (Morquio), VI MPS VI (Maroteaux-Lamy), VII (Sly).
Genetic confirmation is provided for all except Krabbe disease.

Sample requirements, viability, stability:

1. All samples must be collected using DBS-test-kits provided by the CHM to routine pathology laboratories.
2. Sample collection should be done according to the instructions provided in the kit: EDTA samples should NOT be used to spot the blood on the DBS-card.
3. Collection method: heelprick for children younger than 1 year of age & fingerprick for patients older than 1 year of age.
4. DBS-samples must be referred on a separate pathology laboratory requisition number and should not include any other requests/samples.
5. Allow blood to dry on the filter paper at ambient temperature in a horizontal position for at least 4 hours. Avoid exposing DBS-samples to extreme heat OR direct sunlight.

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc.) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Glycosaminoglycan (GAGs/MPS, Total and individual GAG assessment)
URINE

Description

Above price includes the assay and interpretation:
1. Quantitative: Total GAGs.
2. Qualitative interpretation: Absent/present: Heparan sulfate, Dermatan sulfate, Chondriotin Sulfate.
3. Note: Labstix, creatinine and uric acid are included in all urine referals.

Comments

1. This test is utilised in the diagnosis of MPS I, II, III, VI, VII.
2. MPS IV cannot be excluded by the performed analysis.
3. Medication intake may significantly influence the analysis and subsequent result
interpretation.
3. Bacterial-, protein- and blood contamination of the urine sample may result in false positive/negative findings.

Sample requirements, viability, stability:

1. A minimum of 5 ml random urine is required.
2. Sample should be frozen overnight and sent on dry ice.
3. Viability: 12 months – kept frozen.
4. Sample should not be acidified and no preservatives should be added. The former affects the LC-MS/MS base analysis.

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Thin layer chromatography of mono-/oligosaccharides (qualitative)
URINE

Description

Above price includes the assay and interpretation:
1. Qualitative interpretation: mono-/oligosaccharide excretion pattern.
2. Labstix, creatinine and uric acid included in all urine referals.

Comments

1. This test is utilised to evaluate if a monosaccharide-related disorder or oligosaccharidosis
may be present.
2. Medication intake/diet may significantly influence the analysis and subsequent result
interpretation.
3. Bacterial-, protein- and blood contamination of the urine sample may result in false
positive/negative findings.

Sample requirements, viability, stability:

1. A minimum of 5 ml random urine is required.
2. Sample should be frozen overnight and sent on dry ice.
3. Viability: 12 months – kept frozen.
4. NO preservatives should be added.

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Quantitative Organic Acids (Includes orotic acid, includes succinylacetone on request)
URINE

Description

Above price includes the following:
1) Assay, quantification and interpretation.
2) Labstix, creatinine and uric acid included in all urine referals.

Comments

1. This test can be utilised in the diagnosis of an organic aciduria/acidemia and to evaluate
if secondary markers, associated with fatty acid oxidation disorders, are present.
2. Medication intake/diet may significantly influence the analysis and subsequent result
interpretation.
3. Bacterial-, protein- and blood contamination of the urine sample may result in false
positive/negative findings.

Sample requirements, viability, stability:

1. A minimum of 5-7 ml random urine is required. If succinylacetone is requested, the
container should be protected from light (cover in foil) and paperwork should indicate for
succinylacetone analysis.
2. Sample should be frozen overnight and sent on dry ice.
3. Viability: 12 months – kept frozen. Succinylacetone stability: no more than 7 days.
4. NO preservatives should be added.

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by download it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Quantitative Very Long Chain Fatty Acids, Phytanic acid, Pristanic acid
SERUM

Description

Above price includes the assay, quantification (C22, C24, C26, pristanic acid, phytanic acid) and interpretation.

Comments

1. This assay is utilised in the diagnosis of peroxisomal disorders.
2. The intake of peanut butter or a ketogenic diet should be avoided for 48 hours (or longer) before sample collection.

Sample requirements, viability, stability:

1. A fasting sample is required.
2. Other sample requirements: 2 ml SST (yellow top tube) serum required. Sample must be separated, transferred into another tube, frozen overnight and sent on dry ice.
3. Sample collection for patients 3.1) below 18 months of age / 3.2) clinically unstable / 3.3) poor fasting tolerances: should proceed 3-4 hours AFTER feeding / meal​.​
4. Viability: 6 months – kept frozen.

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Pipecolic acid
SERUM

Description

Above price includes the assay, quantification and interpretation

Comments

1. This assay may be utilised as a secondary marker for peroxisomal biogenesis and pyridoxine related disorders.
2. The intake of peanut butter or a ketogenic diet should be avoided for 48 hours (or longer) before sample collection.

Sample requirements, viability, stability:

1. A fasting sample is required.
2. Other sample requirements: 1 ml SST (yellow top tube) serum required. Sample must be separated, transferred into another tube, frozen overnight and sent on dry ice.
3. Sample collection for patients 3.1) below 18 months of age / 3.2) clinically unstable / 3.3) poor fasting tolerances: should proceed 3-4 hours AFTER feeding / meal​.​
4. Viability: 6 months – kept frozen.

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by download it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Quantitative Acylcarnitines
URINE

Description

1. Above price includes the assay, quantification and interpretation.
2. Labstix, creatinine and uric acid included in all urine referals.

Comments

1. Test is informative with regards to carnitine uptake disorders and short/medium chain fatty acid disorders.
2. Medication intake may significantly influence the analysis and subsequent result interpretation.
3. Bacterial-, protein- and blood contamination of the urine sample may result in false positive/negative findings.

Sample requirements, viability, stability:

1. A minimum of 2 ml random urine is required.
2. Sample should be frozen overnight and sent on dry ice.
3. Viability: 12 months – kept frozen.
4. NO preservatives should be added.

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Quantitative Acylcarnitines
SERUM

Description

Above price includes the assay, quantification and interpretation

Comments

1. This test is informative with regards to the presence of carnitine transporter related disorders, fatty acid oxidation disorders and is supportive in the diagnosis of organic acidemias.
2. Medication intake may significantly influence the analysis and subsequent result interpretation.
3. Protein- and blood contamination of the serum sample may result in false positive / negative findings.

Sample requirements, viability, stability:

1. A minimum of 1 ml SST (yellow top tube) serum (pre-prandial) is required.
2. Sample must be separated, transferred into another tube, frozen overnight and sent on dry ice.
3. A haemolysed sample is NOT viable for testing as this may lead to the reporting of falsely elevated long-chain acylcarnitine.
4. Viability: 6 Months kept frozen

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Quantitative Acylcarnitines
DRIED BLOOD SPOT

Description

Above price includes the assay, quantification and interpretation

Comments

1. This test is informative with regards to carnitine transporter related disorders. 2. Medication intake may significantly influence the analysis and subsequent result interpretation.

Sample requirements, viability, stability:

1. One dried blood spot [DBS] sample – 4 complete circles.
2. Keep in sealed paper envelope after dried according to requirements; send separate from other wet specimens and within 2 days after collection. Humidity and extreme temperature may influence the stability of metabolites.
3. Viability: 1 month, kept in a dry, cool place.

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Quantitative Amino Acids
URINE

Description

Above price includes the pre-analytical assessment of the sample (labstix, creatinine and uric acid) and subsequent analysis, quantification and interpretation. Quantitative reporting for: Alanine, alpha-aminobutyric acid, asparagine, alpha-aminoadipic acid, anserine, arginine, argininosuccinic acid, beta-alanine, beta-aminoisobutyric acid, carnosine, citrulline, cystine, cystathionine, ethanolamine, glutamine, histidine, homocystine, homocitrulline, 4-hydroxyproline, isoleucine, leucine, lysine, methionine, 1-methylhystidine, 3-methylhistidine, phosphoethanolamine, phosphoserine, proline, phenylalanine, ornithine, pipecolic acid, S-adenosylhomocysteine, sarcosine, saccharopine, serine, taurine, threonine, tyrosine, tryptophane, serine, valine. Qualitative if requested: Sulfocysteine (marker for Molybdenum-cofactor deficiency).

Comments

1. This test is informative with regards to amino acid transporter related disorders including cystinuria as well as supportive profiling for amino acidopathies.
2. Medication intake may result in the secondary elevation of glycine concentration.
3. Aspartic acid- and glutamic acid levels are not reported due to the unpredictibily of their stability in biological samples.
4. Bacterial-, protein- and blood contamination of the urine sample may result in false positive/negative findings.
5. Labstix, creatinine and uric acid included in all urine referals.

Sample requirements, viability, stability:

1. A minimum of 2 ml random urine is required for total amino acid profile
2. In case of a 24 hour cystine excretion request to rule out cystinuria the excreted volume per day should be documented on the request form as this is required to report the concentration in µmol/day. a 10 ml aliquote of the 24 hour excretion should be refered to CHM
2. Sample should be frozen overnight and sent on dry ice.
3. Viability: 12 months – kept frozen.
4. Sample should not be acidified and no preservatives should be added. The former affects the LC-MS/MS base analysis

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Quantitative Amino Acids
SERUM

Description

Above price includes the analysis of the sample, quantification and interpretation. Quantitative reporting for: Alanine, alpha-aminobutyric acid, asparagine, alpha-aminoadipic acid, anserine, arginine, argininosuccinic acid, beta-alanine, beta-aminoisobutyric acid, carnosine, citrulline, cystine, cystathionine, ethanolamine, glutamine, histidine, homocystine, homocitrulline, 4-hydroxyproline, isoleucine, leucine, lysine, methionine, 1-methylhystidine, 3-methylhistidine, phosphoethanolamine, phosphoserine, proline, phenylalanine, ornithine, pipecolic acid, S-adenosylhomocysteine, sarcosine, saccharopine, serine, taurine, threonine, tyrosine, tryptophane, serine, valine. Qualitative if requested: Sulfocysteine (marker for Molybdenum-cofactor deficiency).

Comments

1. This assay can be utilised to rule in or exclude amino acidopathies.
2. Medication intake may result in the secondary elevation of the glycine concentration.
3. Aspartic acid- and glutamic acid levels are not reported due to the unpredictibily of their stability in biological samples.
4. Protein- and blood contamination of the serum sample may result in false positive/negative findings.

Sample requirements, viability, stability:

1. A minimum of 1 ml SST (yellow top tube) serum is required.
2. Sample must be separated, transferred into another tube, frozen overnight and sent on dry ice.
3. A haemolysed sample is NOT viable for testing as this may lead to the reporting of false positive / negative findings, specifically with regards to ornithine- and arginine levels.
4. Viability: 6 Months kept frozen

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Quantitative Amino Acids
DRIED BLOOD SPOT

Description

1. Above price includes the assay, quantification and interpretation of selected amino acids including citrulline, tyrosine, phenylalanine, methionine, isoleucine/leucine, valine.
2. List will be exdented in 2024 after validation of other amino acids.

Comments

1. This analysis can be utilsed to only rule in or exclude amino acid related disorders associated with abovementioned amino acids.
2. Medication intake may significantly influence the analysis and subsequent result interpretation.

Sample requirements, viability, stability:

1. One dried blood spot [DBS] sample – 4 complete circles.
2. Keep in sealed paper envelope after dried according to requirements; send separate from other wet specimens and within 2 days after collection. Humidity and extreme heat temperatures may influence the stability of metabolites.
3. Viability: 1 month, kept in a dry, cool place.

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE the clinical history form from our website and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Quantitative Phenylalanine
DRIED BLOOD SPOT

Description

Above price includes the assay, quantification and interpretation

Comments

1. This test can be utilised in the diagnosis of hyperphenylalaninemia (including PKU) and treatment monitoring of the related condition.
2. Analysis are done on Tuesdays and Thursdays of each week.

Sample requirements, viability, stability:

1. One dried blood spot [DBS] sample – 4 complete circles.
2. Keep in sealed paper envelope after dried according to requirements; send separate from other wet specimens and within 2 days after collection. Humidity and extreme heat temperature may influence the stability of metabolites.
3. Viability: 1 month, kept in a dry, cool place.

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Quantitative Glycine Specific Assay
CSF + SERUM

Description

Above price includes the assay , quantification and interpretation

Comments

1. This assay is utilised to evaluate if non-ketotic hyperglycinemia (NKHG) is present/absent.
2. Medication (mostly anti-convulsant) intake may significantly influence the analysis and subsequent result interpretation.
3. Blood contaminated CSF sample is NOT viable for testing as this may lead to a false positive diagnosis. Haemolysis of the serum may to some extent influence the result interpretation and should be avoided.

Sample requirements, viability, stability:

 Serum + CSF required (same sample date)
1. 2 ml SST serum (yellow top), spun down, separated, transferred to another tube, kept frozen), sent on dry ice AND
2. 1 ml CSF (cerebrospinal fluid) sample, kept frozen, sent on dry ice.
Viability: 6 months – kept frozen

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Intact glycoprotein (transferrin) analysis to screen for congenital disorders of glycosylation (CDG)
SERUM

Description

Above price includes the assay, quantification and interpretation

Comments

1. This test is utilised in the diagnosis of congential disorders of glycosylation. This include type 1 and to some extent type 2 subtypes. Some CDGs (such as ALG13-CDG) do not present with an abnormal glycoprotein profile.
2. Blood transfusion may influence the analysis. We recommend this test 2 weeks after transfusion to prevent false negative results.

Sample requirements, viability, stability:

1. A minimum of 2 ml SST (yellow top tube) serum is required.
2. Sample must be separated, transferred into another tube, frozen overnight and sent on dry ice.
3. A haemolysed sample is NOT viable for testing as this may lead to the reporting of false positive / negative findings.
4. Viability: 6 Months kept frozen.

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Trimethylaminuria (TMAU): Quantitative TMA (trimethylamine) and FMO3 gene sequencing URINE + EDTA BLOOD

Description

Above price includes the assay, quantification and interpretation

Comments

1. NO preservatives or acidification should be added to the urine samples. 2. No random sample without TMA loading will be tested to avoid false negative. 3. TMA loading is a requirement for this assay – additional information on the loading protocol and collection procedure is available upon request (pliem@nwu.ac.za).

Sample requirements, viability, stability:

1. A minimum of 10 ml urine collected at each time interval is required AND 1x EDTA (purple top) sample at the end of the loading assay.
2. Keep samples frozen at all times. Samples must reach CHM lab within 72 hours after completion of the loading test to assure stability of TMA in the urine samples.
3. Viability: Samples must reach our laboratory within 72 hours after loading assay was performed.

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results (including helicobacter Pylori) of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Biotinidase Enzyme Activity Determination
DRIED BLOOD SPOT

Description

Above price includes the assay, quantification and interpretation

Comments

1. This test is utilised in the diagnosis of profound or partial biotinidase deficiency.
2. Blood transfusion may influence the analysis. We recommend this test 72hrs collection
after the transfusion to avoid false negative findings.

Sample requirements, viability, stability:

1. 1x Dried blood spot [DBS] sample – 4 complete circles.
2. Keep in sealed paper envelope after dried according to requirements, send separate from
other wet specimens and within 2 days after collection.
3. Humidity and extreme temperatures may influence the stability of the biotinidase activity.
4. Viability: 1 year – kept frozen.

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Quantitative Galactose-1-Phosphate
DRIED BLOOD SPOT

Description

Above price includes the assay, quantification and interpretation

Comments

This test is used primarily for monitoring of galactosemia patients on treatment. It can also be used diagnostically, provided that the patient is not on a lactose free diet. It is particularly useful when a patient has received a recent blood transfusion.

Sample requirements, viability, stability:

1. 1x Dried blood spot [DBS] sample – 4 complete circles.
2. Keep in sealed paper envelope after dried according to requirements, send separate from other wet specimens and within 2 days after collection. Humidity and extreme temperature may influence the stability of metabolites.
3. Viability: 1 month, kept in a dry, cool place.

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Mitochondrial respiratory chain enzyme analyses (NHLS)
MUSCLE

Description

Above price includes the assay, quantification and result interpretation for complexes I, II, II+III, III, IV and citrate synthase.

Comments

1. This analysis is utilized to rule in or evaluate if mitochondrial complex I, II, combined II+III, III or IV may be present.
2. Providing the blood lactate, lactate/pyruvate ratio result (performed at routine pathology laboratories) is advised when submitting the sample for testing.

Sample requirements, viability, stability:

1. A minimum of 100 mg skeletal muscle sample (preferably from vastus lateralis) is required (size: ± half the size of a ten cent coin). 2. The biopsy must be placed as is (without any additional preservatives or liquids) in a 1.5ml Eppendorf tube (eppie) on dry ice, IMMEDIATELY after the muscle was collected. 3. Freeze the tube with sample immediately after collection at -80°C. The sample should be stored at -80°C until it can be transported to our laboratory.

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc.) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Immunoreactive trypsinogen (IRT) neonates <24 days
DRIED BLOOD SPOT

Description

Above price includes the assay, quantification and interpretation

Comments

This test can be utilsed as a screening assay for cystic fibrosis in neonates and early infancy ( < 24 days of life).

Sample requirements, viability, stability:

1. One dried blood spot [DBS] sample – 4 complete circles.
2. Keep in sealed paper envelope after dried according to requirements; send separate from other wet specimens and within 2 days after collection. Humidity and extreme temperature may influence the stability of metabolites.
3. Viability: 1 month, kept in a dry, cool place.

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according POPIA regulation.
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE and send it with sample/email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Mitochondrial respiratory chain enzyme analyses (PRIVATE)
MUSCLE

Description

Above price includes the assay, quantification and result interpretation for complexes I, II, II+III, III, IV and citrate synthase.

Comments

1. This analysis is utilized to rule in or evaluate if mitochondrial complex I, II, combined II+III, III or IV may be present.
2. Providing the blood lactate, lactate/pyruvate ratio result (performed at routine pathology laboratories) is advised when submitting the sample for testing.

Sample requirements, viability, stability:

1. A minimum of 100 mg skeletal muscle sample (preferably from vastus lateralis) is required (size: ± half the size of a ten cent coin). 2. The biopsy must be placed as is (without any additional preservatives or liquids) in a 1.5ml Eppendorf tube (eppie) on dry ice, IMMEDIATELY after the muscle was collected. 3. Freeze the tube with sample immediately after collection at -80°C. The sample should be stored at -80°C until it can be transported to our laboratory.
4. The samples must be shipped on dry ice and sent early in the week to prevent weekend delivery delays. 5. Important: Samples will not be analyzed if above protocol is not followed.

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc.) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Galactose-1-phosphate uridyltransferase (GALT) Enzyme Activity
DRIED BLOOD SPOT

Description

Above price includes the assay, quantification and interpretation

Comments

1. This test is utilised in the diagnosis of profound or partial GALT deficiency.
2. A blood transfusion during a 6 week period prior to sample collection may result in false negative results. The test is not recommended during this period.

Sample requirements, viability, stability:

1. 1x Dried blood spot [DBS] sample – 4 complete circles.
2. Keep in sealed paper envelope after dried according to requirements, send separate from other wet specimens and within 2 days after collection. Humidity and extreme temperature may influence the stability of the biotinidase activity.
3. Viability: 1 month, kept in a dry, cool place.

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

Full Metabolic Evaluation
URINE

Description

Biochemical analyses, quantification/qualification and interpretation: U-Creatinine, U-Uric Acid, U-Labstix, U-Reducing substances, QU-Organic acids, U-TLC-Oligosaccharides, U-MPS-DMB-screen, U-MPS GAGs LCMS/MS, QU-Amino Acids, QU-Carnitine profile.

Comments

1. This test can be utilised to rule in or exclude: amino acidurias, organic acidemias / acidurias, some fatty acid oxidation disorders, carbohydrate related disorders as well as mucopolysaccharidosis. Adding serum amino acids and acylcarnitines to the profile may be more informative with regards to amino acidopathies, carnitine transporter related disorders as well as the full spectrum of fatty acid oxidation disorders. The full profile does not exclude all known inborn errors of metabolic disorders, as biomarkers for some may be limited.
2. Medication intake/diet may significantly influence the analysis and subsequent result interpretation.
3. Bacterial- and blood contamination of the urine sample may result in false positive / negative findings.

Sample requirements, viability, stability:

1. A minimum of 10-15 ml random urine is required.
2. Sample should be frozen overnight and sent on dry ice.
3. Viability: 12 months – kept frozen. Succinylacetone stability: no more than 7 days.
4. NO preservatives should be added.

Information Required with sample(s):

Absent clinical details may affect the interpretation of results and recommendations for further/additional testing and subsequent diagnosis of a metabolic disorder. Consent to use below information (point 4) is required according to POPIA regulation:
1. Clinical history of the patient. The referring clinician can complete the clinical history form by downloading it HERE and send it with the sample or email it to pliem@nwu.ac.za.
2. Other relevant medical reports (e.g. MRI brain, EEG, X-Ray reports, sonar reports, biopsy reports, genetic testing reports, etc) which may assist in the diagnosis of a metabolic disorder can be emailed to pliem@nwu.ac.za.
3. Cumulative, routine pathology results of the patient (including archive results available) – this must be provided and emailed to pliem@nwu.ac.za by the referring pathology laboratory.
4. Please complete the short consent form and also indicate if the patient/family would like to be contacted by our rare disease biobank.

GCxGC-TOFMS Untargeted

Compound list

Spectra identified via comparison with library spectra

NMR Untargeted

Compound list

Spectra identified via comparison with library spectra

LDL Cholesterol Subfractions

Compound list

The LDL subfraction test measures up to twelve lipoprotein fractions and subfractions (VLDL, mid-bands A-C and LDL 1 through 7)

HDL Cholesterol Subfractions

Compound list

Separates and quantifies up to 10 HDL subfractions, classified from large buoyant HDL lipoproteins (HDL-L) to small-dense HDL lipoproteins (HDL-S).