Newborn Screening for IEMs

Biochemical Genetics and National Expanded Newborn Screening (NENS) Laboratory

About Us

The National Expanded Newborn Screening Programme aims to provide screening for inborn errors of metabolism (IEM) to all babies born in Singapore. Screening the babies early in life helps early detection and treatment of various metabolic disorders before the onset of symptoms. Individually, these disorders are very rare, but as a whole it affects about 1 in 3000 births in Singapore.

Newborn screening is recognized internationally as an essential preventative health scheme for the detection of metabolic disorders that can affect the health of the baby in the long run. Newborns typically appear well at birth, but if left undiagnosed, these disorders may lead to developmental delay, poor growth, severe illness, brain damage and in some cases even death.

The Biochemical Genetics Laboratory was also established along with the Newborn Screening Programme to provide confirmatory tests for newborn screening cases, diagnostic tests (IEM cases for neonates, children and adults) as well as patient monitoring services of positive cases.

Accreditations

SAC-SINGLAS (ISO 15189)

Click here for frequently asked questions.

Resources

Information Pamphlets

Tests Available

Newborn Screening Tests - Metabolic Screening only

Purpose of Test	Metabolic Screening by Tandem Mass Spectrometry For early detection of more than 30 clinically important metabolic disorders in the following categories : Organic Acid Disorders Fatty Acid Oxidation Disorders Amino Acids Disorders Click here for more information and conditions screened.
Specimen Requirements	Heel pricked blood collected on Whatman 903 Filter paper. To request from the NENS lab if necessary. Do ensure that at least 3-5 blood spots are collected.
Handling	Ideally samples should be collected between 24 and 72 hours after birth. Card must be dried for 3-4 hours, placed in an envelope and sent to the laboratory.

Newborn Screening Tests - Metabolic screening + Galactosaemia

Purpose of Test	Metabolic Screening by Tandem Mass Spectrometry For early detection of more than 30 clinically important metabolic disorders in the following categories : Organic Acid Disorders Fatty Acid Oxidation Disorders Amino Acids Disorders Click here for more information and conditions screened. Metabolic Screening by Tandem Mass Spectrometry For early detection of more than 30 clinically important metabolic disorders in the following categories :
Specimen Requirements	Heel pricked blood collected on Whatman 903 Filter paper. To request from the NENS lab if necessary. Do ensure that at least 3-5 blood spots are collected.
Handling	Ideally samples should be collected between 24 and 72 hours after birth. Card must be dried for 3-4 hours, placed in an envelope and sent to the laboratory.

Newborn Screening Tests - Metabolic screening + Galactosaemia and Cystic Fibrosis

Purpose of Test	Metabolic Screening by Tandem Mass Spectrometry For early detection of more than 30 clinically important metabolic disorders in the following categories : Organic Acid Disorders Fatty Acid Oxidation Disorders Amino Acids Disorders Click here for more information and conditions screened. Galactosaemia Screening To screen for conditions that affect the infant’s ability to break down galactose (a form of sugar) properly. Cystic Fibrosis Test To detect cystic fibrosis, an inherited condition that can cause severe damage to the lungs and digestive system. Visit http://www.cff.org/AboutCF/ for more information.
Specimen Requirements	Heel pricked blood collected on Whatman 903 Filter paper. To request from the NENS lab if necessary. Do ensure that at least 3-5 blood spots are collected.
Handling	Ideally samples should be collected between 24 and 72 hours after birth. Card must be dried for 3-4 hours, placed in an envelope and sent to the laboratory.

Newborn Screening Tests - Plasma Acylcarnitine

Useful For	Detecting fatty acid oxidation disorders and several organic acidurias. Evaluating and monitoring patients with fatty acid oxidation and organic acid disorders.
Clinical Indication	hypoketotic hypoglycemia variable degrees of liver disease and/or failure skeletal myopathy, dilated/hypertrophic cardiomyopathy sudden or unexpected death
Reference Range	Click here.
Interpretation	The individual quantitative results are not diagnostic by themselves, and are used in order to provide an overall interpretation of the acylcarnitine profile. Interpretation of results is based on pattern recognition. Do note that abnormal results are not sufficient to establish a diagnosis of a particular disease. In order to provide confirmation of preliminary diagnosis, independent biochemical and molecular genetic tests are required.
Specimen Requirements	1-2 ml lithium heparin blood (ideally separated within 1hr of sample collection).
Handling	Send with ice; separate and store plasma @ -20°C if not dispatched immediately.

Biochemical Genetics Tests - Organic Acids

Useful For	Detecting a variety of inherited metabolic disorders, including the classical organic acidaemias, fatty acid oxidation disorders, urea cycle defects and some amino acidopathies.
Clinical Indication	Metabolic crisis (acidosis, hypoglycaemia, hyperammonaemia) Clinical features of systemic intoxication Unexplained hepatopathy Ketonuria, cytopenia
Interpretation	Having an abnormal organic acid profile is not sufficient to conclude a particular disorder. Interpretation is based on correlation of positive and negative findings as well as the overall pattern in the profile.
Specimen Requirements	3 to 10 ml fresh urine, no preservative (sterile container).
Handling	Send with ice; store @ -20°C if not dispatched immediately.

Biochemical Genetics Tests - Quantitative Oroic Acids

Useful For	Evaluating the differential diagnosis of hyperammonemia and hereditary orotic aciduria. For female patients, it may be helpful in determining carrier status or exclude OTC deficiency after an allupurinol loading test.
Clinical Indication	failure to thrive mental and physical retardation
Interpretation	The interpretation of the result must be correlated with clinical and laboratory findings. The value of the orotic acid concentration is reported.
Specimen Requirements	3 to 10 ml fresh urine, no preservative (sterile container).
Handling	Send with ice; store @ -20°C if not dispatched immediately.
Reference Range	0 to 3.5 µmol/mmol creatinine.

Biochemical Genetics Tests - Quantitative Methylmalonic Acid

Useful For	Determining the significance of an apparently elevated excretion on qualitative organic acid analysis Monitoring patients with methylmalonic acidaemia
Clinical Indication	neonatal or infantile metabolic ketoacidosis failure to thrive developmental delay
Interpretation	A significant increase of methylmalonic acid concentration in urine supports a diagnosis of methylmalonic acidemia.
Specimen Requirements	3 to 10 ml fresh urine, no preservative (sterile container).
Handling	Send with ice; store @ -20°C if not dispatched immediately.
Reference Range	0.001-0.008 mmol/mmol creatinine (1-8 µmol/mmol creatinine).

Biochemical Genetics Tests - Amino Acids - Full Quantitation
Plasma

Useful For	Detecting disorders such as phenylketonuria(PKU), tyrosinaemia, maple syrup urine disease(MSUD), cystinuria, non-ketotic hyperglycinaemia and the urea cycle disorders. Monitoring the efficacy of treatment in patients with these disorders, as well as patients on low protein diets for other reasons (eg. those with organic acidaemias).
Clinical Indication	acute life-threatening episode failure to thrive recurrent vomiting neurological deterioration hyperammonaemia lethargy metabolic acidosis testing or following therapy for a specific inborn error of metabolism (PKU, MSUD, tyrosinemia, etc.).
Interpretation	A detailed interpretation requires the overview of results and correlation to available clinical information. Further steps such as additional biochemical and in vitro studies (enzyme & molecular analysis) may be needed to confirm and provide differential diagnosis of the disorders.
Specimen Requirements	1 ml lithium heparin blood (ideally separated within 1hr of sampling).
Handling	Send with ice; separate and store plasma @ -20°C if not dispatched immediately.
Reference Range	Click here.

Urine

Useful For	Detecting disorders such as phenylketonuria(PKU), tyrosinaemia, maple syrup urine disease(MSUD), cystinuria, homocystinuria and the urea cycle disorders. Monitoring the efficacy of treatment in patients with these disorders, as well as patients on low protein diets for other reasons (eg. those with organic acidaemias).
Clinical Indication	acute life-threatening episode failure to thrive recurrent vomiting neurological deterioration hyperammonaemia lethargy metabolic acidosis testing or following therapy for a specific inborn error of metabolism (PKU, MSUD, tyrosinemia, etc.).
Interpretation	A detailed interpretation requires the overview of results and correlation to available clinical information. Further steps such as additional biochemical and in vitro studies (enzyme & molecular analysis) may be needed to confirm and provide differential diagnosis of the disorders.
Specimen Requirements	3 ml fresh urine, no preservative (sterile container).
Handling	Send with ice; separate and store plasma @ -20°C if not dispatched immediately.
Reference Range	Click here.

CSF

Useful For	Detecting disorders such as non-ketotic hyperglycinaemia (NKH)
Clinical Indication	lethargy hypotonia poor feeding abnormal jerking movements breathing difficulty
Interpretation	A detailed interpretation requires the overview of results and correlation to available clinical information. Further steps such as additional biochemical and in vitro studies (enzyme & molecular analysis) may be needed to confirm and provide differential diagnosis of the disorders.
Specimen Requirements	Minimum 200 µl in sterile container; no preservative. Note : Blood stained CSF specimen is unsuitable.
Handling	Send with a paired plasma sample (collected in lithium heparin within an hour as interpretation requires comparison with plasma concentrations.) Send with ice; store @ -20°C if not dispatched immediately
Reference Range	Click here.

Biochemical Genetics Tests: Gal-1-P-Uridyl Transferase

Useful For	The screening test aims to identify homozygote GALT deficient patients.
Clinical Indication	Progressive symptoms after start of milk feeds Vomiting Diarrhoea Jaundice
Interpretation	Normal sampls fluoresce brightly at one or two hours. An activity of <10% must be further investigated. Patients with activity >25% will either be heterozygote or Duarte variants. Normal activity with high total galactose results may require galactose assay to investigate for epimerase or galactokinase deficiency.
Specimen Requirements	0.5 ml lithium heparin blood (do not separate / freeze)
Handling	Send immediately; store in fridge @ 4°C if not dispatched immediately.

Biochemical Genetics Tests: Sterols

Useful For	Measuring plasma levels of Cholestanol, Cholesterol and 7-Dehydrocholesterol. The level of cholestanol is diagnostic for the disorder Cerebrotendinous xanthomatosis. The build up of cholestanol in tendon and neural tissues causes ataxia, dementia and eventually death from the fourth decade. It is often associated with high plasma cholesterol. Abnormal levels of 7-Dehydrocholesterol is diagnostic of the Smith-Lemi-Opitz syndrome.
Clinical Indication	Microcephaly, dysmorphic features, variable skeletal dysplasies, growth and mental retardation as well as heart and kidney defects. The most consistent clinical feature is 2nd and 3rd toes syndactyly.
Interpretation	A detailed interpretation requires the overview of results and correlation to available clinical information.
Specimen Requirements	1 ml lithium heparin blood (ideally separated within 1 hour of sampling and kept away from direct sunlight)
Handling	Send with ice; separate and store plasma @ -20°C if not dispatched immediately.
Reference Range	Cholestanol Normal: 3-16 mmol/L Affected Range: 33 - 386 mmol/L Cholesterol Normal: 600 – 6500 mmol/L (all ages) 7-Dehydrocholesterol Normal: Less than 1.5 mmol/L Affected Range: 5.2 - 1221 mmol/L

Biochemical Genetics Tests: VLCFA (Very Long Chains Fatty Acids Test)

Useful For

Measuring the following VLCFAs: docosanoic acid (C22), tetracosanoic acid (C24), hexacosanoic acid (C26) and branch-chain fatty acids such as phytanic acid and pristanic acid.
A significant proportion of inherited disorders of peroxisomal biogenesis feature abnormal concentrations of VLCFAs in blood and tissues.
Phytanic acid and pristanic acid are both markers for peroxisome biogenesis disorders as well as specific isolated defects affecting their oxidation.

Clinical Indication

Skeletal abnormalities
Dysmorphic features
Hyperintestinal dysfunction

Interpretation

Plasma very long chain fatty acids are elevated in peroxisomal disorders such as Adrenoleukodystrophy (ALD). Refsum disease and Zellweger Syndrome. Phytanic acid may also be raised in Refsum's disease.

Specimen Requirements

1 ml lithium heparin blood (ideally separated within 1hr of sampling)

Handling

Send with ice; separate and store plasma @ -20°C if not dispatched immediately.

Reference Range

Docosanoic acid (C22)	30-112 µmol/L
Tetracosanoic acid (C24)	14-80 µmol/L
Hexacosanoic acid (C26)	0.33-1.50 µmol/L
C24:22	0.44-1.05
C26:22	0.005-0.030
Pristanic acid	0.00-2.0 µmol/L
Phytanic acid	0.2-19.3 µmol/L

Contact Us

Biochemical Genetics and National Expanded Newborn Screening Laboratory
Department of Pathology and Laboratory Medicine
KK Women’s and Children’s Hospital
Children’s Tower, Basement 1
100 Bukit Timah Road
Singapore 229899

Phone: (65) 6394 5049/8728
Fax: (65) 6394 3773
Email for enquires:
Metabolic.Newborn.Screening@kkh.com.sg

If a sample was not collected from your baby and you would like to have the test done, please contact the hospital/paeditrician where your baby was delivered to arrange for the test. However, it is also possible to contact our nurse coordinator on 81217855 and arrange for sample collection at one of our walk-in clinics at KKH.