' where nid = '87'; update frontpage set ctx = '

Our mission

Our History

Newborn Screening Center in National Taiwan University Hospital (NTUH) has been established since 1983, at the same time, the Department of Health (DOH) of the Government started taking over the pilot mass newborn screening (NBS) studies and providing funds to the NBS screening laboratory. Blood spot NBS using biochemical markers to detect certain congenital conditions are a public health activity aimed at the early identification and treatment/management of newborns. In Taiwan, mass newborn screening has officially became the national neonatal mass screening program in 1985. In 1983, the medical genetic counseling center at NTUH was established to act as clinical networks for inborn errors of metabolism. Therefore, being an academic hospital center, we act in 3 different roles, which are, newborn's hospital, screening laboratory, and referral hospital. Thus, we are able to provide the closest connection in the infrastructure of newborn screening and manage our screening performance based on our monitoring and treatment results. In 2006, Taiwan Accreditation Foundation (TAF), the only national accreditation association in Taiwan, accredited us in Medical Testing.

Our service

At first, we provided only five diseases screening, including congenital hypothyroidism, phenylketonuria, homocystinuria, galactosemia, and glucose-6-phosphate dehydrogenase deficiency, as Department of Health (DOH) recommendation. Since 2000, we were the first center that included screening for CAH, and expanding metabolic screening using MS/MS in 2001. Those diseases have been adapted into the universal panel of national screening program since 2006. In 2005, we provided newborn screening for Pompe disease. This is the first large-scale Pompe screening in the world. Our results proved that newborn screening for Pompe disease is feasible, and early diagnosis through newborn screening provided better treatment/health outcome to patients. We continue to develop and provide new screening tests, such as Methylmalonic acid detection since 2008, Severe combined immunodeficiency disease (SCID) since 2010, and Aromatic L-amino acid decarboxylase (AADC) deficiency since 2013.

We aim to provide every newborn a timely screening equally. The coverage rate of Taiwan newborn screening is over 99.9%. Till year 2012, we have provided screening to over 3.4 M newborns. In NTUH, almost 100% of of samples are tested within 72 hours after receiving. Around 98.5% of results came out within 8 days after birth. Therefore, the newborns can have appropriate treatment timeline to improve the outcome.

Our achievement

Congenital hypothyroidism (CHT): This disorder is characterized by decreased or nearly absence of thyroid hormone production. Permanent primary congenital hypothyroidism in Taiwan occurs in about one of every 5,000 newborns. Mental retardation is a major sequel of delayed treatment for congenital hypothyroidism; congenital hypothyroidism can be treated early if detected with neonatal screening. The mean intelligence quotient (IQ) score is 102 +/- 18 for CHT patients detected by neonatal screening. The severity of hypothyroidism at diagnosis is the most important prognostic factor affecting intellectual outcome in these patients.

Phenylketonuria (PKU): The incidence of this disorder in Taiwan is around 1 in 20,000-40,000 newborns. These infants have missing or deficient enzyme which cannot properly process the amino acid phenylalanine. Without treatment, phenylalanine could be accumulated and cause mental retardation. In Taiwan, tetrahydrobiopterin (BH4) deficiency accounts for one third of patients, and most of patients have defect in 6-pyruvoyltetrahydropterin synthase (6-PTPS). Combination treatment of BH4, levodopa and 5-hydroxytryptophen (5-HTP) for BH4 deficiency patients as early as possible can ensure patient living with a normal intelligence if the prenatal brain damage is not severe. Other patients have defect in phenylalanine hydroxylase (PAH) need life-long diet restriction of phenylalanine; some of them may be benefit from BH4 supplement. Their average IQ scores are within normal ranges. However, patients with classical PKU (more severe patients) tend to have poor control of blood phenylalanine levels and thus lower IQ scores than other patients.

Homocystinuria: This is an inherited disorder of amino acid methionine metabolism, which occurs in approximately less than 1 in 1,500,000 births. This disease is detected by screening methionine levels in dried blood spots. Methionine adenosyltransferase deficiency is the most prevalent cause of isolated hypermethioninemia in Taiwan, and the defect is inherited either by autosomal dominant or autosomal recessive pattern.

Glucose-6-phosphate dehydrogenase deficiency (Favism): This is the most common enzyme deficiency in the Taiwan area, with an incidence of 1.8 out of every 100 births (in male 2.8%, in female 0.7%). Hemolytic anemia can occur in response to ingestion of fava (broad) beans and certain drugs or severe infection, leading to severe complications and even death. Newborn screening provides the awareness so that parents can take preventive procedures.

Congenital adrenal hyperplasia (CAH): The incidence of this disorder in Taiwan is around 1 in 15,000 births. Without screening program, CAH newborns may be missed, even though they have a life-threatening illness. By newborn screening, patients can be identified before clinical events, diagnosis, and even before development of adrenal crisis.

Glutaric acidemia type I (GA I): The incidence of this disorder in Taiwan is around 1 in 70,000-100,000 births. Deficiency in the enzyme glutaryl-CoA dehydrogenase leads to buildup amino acids lysine, hydroxylsine and tryptophan, which are all toxic to the brain. If left untreated, patients can suffer from various symptoms, including loss of motor control, decreased muscle tone and muscle rigidity. Newborn screening of GA I is performed by measuring blood spots glutarylcarnitine (C5DC) levels. All patients were treated prior to 1 month of age, including 6 patients who we have followed up. Among these 6 patients, four of them have normal intelligence, and the other two experienced encephalopathic crisis episodes and delayed development, but the brain lesions were resolved.

Methylmalonic acidemia (MMA): The incidence of this disorder in Taiwan is still around 1 in 70,000-100,000 births. This is an organic acid disorder in which certain waste products cannot be removed from the blood. If an acute episode of clinical event is not prevented, it can lead to developmental delays, coma, seizures and even death. Tandem mass spectrometry has made early detection possible. We have followed 5 patients who were identified by newborn screening for elevated propionylcarnitine (C3-carnitine) levels. When treated at a median age of 11 days, 2 (40%) of patients were asymptomatic, one (20%) was significantly acidotic, but all had various degrees of hyperammonemia. Magnetic resonance imaging of the brain was performed in 4 patients shortly after diagnosis, and the results were all abnormal. There was no further metabolic decompensation after the initial episodes, but their mean developmental quotient was only 50. Liver transplantation has been suggested to be a solution to this disease. We also demonstrated that liver transplantation stabilized blood MMA level, therefore patients can be away from suffering frequent metabolic decompensation and have better protein tolerance and better quality of life.

Carnitine transporter defect

Carnitine uptake defect (CUD) is an autosomal recessive fatty acid oxidation defect caused by a deficiency of the high-affinity carnitine transporter OCTN2. CUD patients may present with hypoketotic hypoglycemia, hepatic encephalopathy or dilated cardiomyopathy. Tandem mass spectrometry screening of newborns can detect CUD. Newborn screening allows the detection of CUD both in newborns and mothers, with an incidence in newborns of one in 67,000 and a prevalence in mothers of one in 33,000. Detection of CUD in mothers may prevent them from developing dilated cardiomyopathy.

Citrin deficiency

Citrin is a mitochondrial membrane aspartate-glutamate carrier, and citrin deficiency causes hyperammonaemia in adults (adult-onset type II citrullinaemia, CTLN2), and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in infants. Patients with NICCD often present with jaundice, fatty liver, or even liver failure. The incidence estimated by gene frequency is around 1 in 20,000 newborns. Newborn screening for citrin deficiency has been shown to result in early treatment for newborns suffering from NICCD, or preventing erroneous management if CTLN2 develops in these patients.

Fatty acid oxidations defect

Fatty acid oxidations defect includes a group of enzyme defects presenting with similar heterogeneous clinical phenotypes of different severity. In the past, these are ultra-rare disorders in Chinese; however, it is a treatable disease and the incidence is expected to be increased after newborn screening. Through screening, we have identified patients with Carnitine palmitoyltransferase I (CPT I) deficiency, Carnitine palmitoyltransferase II (CPT II) deficiency, Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, short-chain acyl-CoA dehydrogenase (SCAD), and Glutaric acidemia type II.

Pompe disease

Newborn screening for Pompe disease

Fabry disease

Fabry disease (alpha-galactosidase A (alpha-Gal A, GLA) deficiency) is a panethnic inborn error of glycosphingolipid metabolism. Males with no enzyme activity present early-onset classic phenotype, whereas those with residual activity present with the later-onset subtype. We initiated a pilot-screening program, and found a high incidence of Fabry disease in Taiwan; most of them have the later-onset form with the IVS4+919G→A mutation.

Severe combined immunodeficiency disease (SCID)

Severe combined immunodeficiency disease (SCID) is a term that describes a spectrum of primary immunodeficiencies. Patients with SCID usually present healthy at birth but then suffer from life-threatening infections and ultimately die before one year of age if not treated appropriately. Hematopoietic stem cell transplantation before the onset of serious infections improves the long-term prognosis of these patients remarkably. Since 2010, we screened all newborns for SCID by measuring the copy number of T-cell receptor excision circles (TRECs) and RNase P. The incidence of SCID revealed from our study is around 1 in 50,000 newborns, while the incidence of T cell lymphopenia (most are 22q11.2 microdeletion syndrome) in apparently health newborns is more than 1 in 11,000. All SCID patients identified through our newborn screening have received hematopoietic stem cell transplantation at the age of 2-5 month.

Our personnel

Related publications

General screening

• Hwu WL, Huang AC, Chen JS, Hsiao KJ, Tsai WY. Neonatal screening and monitoring system in Taiwan. Southeast Asian J Trop Med Public Health. 2003;34 Suppl 3:91-3.
• Hwu WL, Yu CL. Debate in newborn screening for metabolic disorders in Taiwan--a voluntary screening? Mandatory screening? Or both?Acta Paediatr Taiwan. 2003 May-Jun;44(3):125.
• Huang HP, Chu KL, Chien YH, Wei ML, Wu ST, Wang SF, Hwu WL. Tandem mass neonatal screening in Taiwan--report from one center. J Formos Med Assoc. 105(11):882-6.
• Hsieh SH, Hsieh SL, Chien YH, Weng YC, Hsu KP, Chen CH, Tu CM, Wang Z, Lai F. Newborn screening healthcare information system based on service-oriented architecture. J Med Syst. 2010;34:519-30.
• Niu DM, Chien YH, Chiang CC, Ho HC, Hwu WL, Kao SM, Chiang SH, Kao CH, Liu TT, Chiang H, Hsiao KJ. Nationwide survey of extended newborn screening by tandem mass spectrometry in Taiwan.J Inherit Metab Dis. 2010;33(Suppl 2):S295-305.

Phenylketonuria (PKU)

• Chien YH, Chiang SC, Huang AC, Lin JM, Chiu YN, Chou SP, Chu SY, Wang TR, Hwu WL. Treatment and outcome of Taiwanese patients with 6-pyruvoyltetrahydropterin synthase gene mutations. J Inher Met Dis 2001;24:815-23.
• hien YH, Peng SF, Wang TR, Hwu WL. Cranial magnetic resonance spectroscopy of tetrahydrobiopterin deficiency. Am J Neuroradiol 2002;23:1055-8.
• Chien YH, Chiang SC, Huang A, Chou SP, Tseng SS, Huang YT, Hwu WL. Mutation spectrum in Taiwanese patients with phenylalanine hydroxylase deficiency and a founder effect for the R241Cmutation. Hum Mutat 2004;23(2):206.
• Peng SS, Tseng WY, Chien YH, Hwu WL, Liu HM. Diffusion tensor images in children with early-treated, chronic, malignant phenylketonuric: correlation with intelligence assessment. AJNR Am J Neuroradiol 2004;25(9):1569-74.
• Chien YH, Chiang SC, Huang A, Lin JM, Chiu YN, Chou SP, Wang TR, Hwu WL. Phenylalanine hydroxylase deficiency: intelligence of patients after early dietary treatment. Acta Paediatr Taiwan 2004;45(6):320-3.

Homocystinuria

• Chien YH, Chiang SC, Huang A, Hwu WL. Spectrum of hypermethioninemia in neonatal screening. Early Hum Dev 2005;81:529-33.
• Fernández-Irigoyen J, Santamaría E, Chien YH, Hwu WL, Korman SH, Faghfoury H, Schulze A, Hoganson GE, Stabler SP, Allen RH, Wagner C, Mudd SH, Corrales FJ. Enzymatic activity of methionine adenosyltransferase variants identified in patients with persistent hypermethioninemia. Mol Genet Metab. 2010 Oct-Nov;101(2-3):172-7.

Congenital hypothyroidism (CHT)

• Tsai WY, Lee JS. Congenital hypothyroidism in Taiwan: experience before mass screening. J Formos Med Assoc. 1992;91(9):864-6.
• Tsai WY, Lee JS, Wang TR, Chen JS, Chuang SM. Clinical characteristics of congenital hypothyroidism detected by neonatal screening. J Formos Med Assoc. 1993;92(1):20-3.
• Tsai WY, Lee JS, Chao MC, Chen LY, Lin SJ, Wu KH, Wang TR, Chen JS, Chuang SM. Prevalence of permanent primary congenital hypothyroidism in Taiwan.J Formos Med Assoc. 1995;94(5):271-3.
• Huang CY, Chang TC, Tsai WY, Hsiao YL. Clinical significance of thyrotropin-binding inhibitor immunoglobulin levels in newborns and their mothers. J Formos Med Assoc. 1997;96(12):943-7.
• Hsiao PH, Chiu YN, Tsai WY, Su SC, Lee JS, Soong WT. Intellectual outcome of patients with congenital hypothyroidism detected by neonatal screening. J Formos Med Assoc. 2001;100(1):40-4.

Congenital Adrenal Hyperplasia (CAH)

• Chu SY, Tsai WY, Chen LH, Wei ML, Chien YH, Hwu WL. Neonatal Screening of Congenital Adrenal Hyperplasia in Taiwan-A Pilot Study. J Formosan Med Assoc 2002;101:691-4.

Glucose-6-phosphate dehydrogenase deficiency (G6PD)

• Chien YH, Lee NC, Wu ST, Liou JJ, Chen HC, Hwu WL. Changes in incidence and sex ratio of glucose-6-phosphate dehydrogenase deficiency by population drift in Taiwan. Southeast Asian J Trop Med Public Health. 2008;39(1):154-61.

Methylmalonic acidemia (MMA)

• Lee NC, Chien YH, Peng SF, Huang AC, Liu TT, Wu AS, Chen LC, Hsu LW, Tseng SC, Hwu WL. Brain damage by mild metabolic derangements in methylmalonic acidemia. Pediatr Neurol. 2008;39(5):325-9.
• Chen PW, Hwu WL, Ho MC, Lee NC, Chien YH, Ni YH, Lee PH. Stabilization of blood methylmalonic acid level in methylmalonic acidemia after liver transplantation. Pediatr Transplant. 2010 May;14(3):337-41.
• Cheng KH, Liu MY, Kao CH, Chen YJ, Hsiao KJ, Liu TT, Lin HY, Huang CH, Chiang CC, Ho HJ, Lin SP, Lee NC, Hwu WL, Lin JL, Hung PY, Niu DM. Newborn screening for methylmalonic aciduria by tandem mass spectrometry: 7 years' experience from two centers in Taiwan. J Chin Med Assoc. 2010;73(6):314-8.

Glutaric aciduria type I (GA I)

• Hsieh CT, Hwu WL, Huang YT, Huang AC, Wang SF, Hu MH, Chien YH*. Early detection of glutaric aciduria type I by newborn screening in taiwan. J Formos Med Assoc. 2008;107:139-44.
• Lee CS, Chien YH, Peng SF, Cheng PW, Chang LM, Huang AC, Hwu WL, Lee NC. Promising outcome in patients with glutaric aciduria type I detected by newborn screening. Metab Brain Dis. 2012 Oct 27. [Epub ahead of print]

Other diseases screening by Tandem mass spectrometry

• Kobayashi K, Bang Lu Y, Xian Li M, Nishi I, Hsiao KJ, Choeh K, Yang Y, Hwu WL, Reichardt JK, Palmieri F, Okano Y, Saheki T. Screening of nine SLC25A13 mutations: their frequency in patients with citrin deficiency and high carrier rates in Asian populations. Mol Genet Metab. 2003;80(3):356-9.
• Lee NC, Tang NL, Chien YH, Chen CA, Lin SJ, Chiu PC, Huang AC, Hwu WL. Diagnoses of newborns and mothers with carnitine uptake defects through newborn screening. Mol Genet Metab. 2010;100(1):46-50.
• Hwu WL, Chien YH, Lee NC, Chen PW, Chiang SC. Second tier tests in newborn screening. 日本先天代謝異常???誌Vol.27 No.1: 22-27.
• Chen YC, Chien YH, Chen PW, Tang NL, Chiu PC, Hwu WL, Lee NC. Carnitine uptake defect (primary carnitine deficiency): risk in genotype-phenotype correlation. Human mutation (in press).
• Wang LY, Chen NI, Cheng PW, Chiang SC, Hwu WL, Lee NC, Chien YH. Newborn screening for citrin deficiency and carnitine uptake defect using second tier molecular testing. BMC Med Genet (in revision).

Pompe disease

Newborn screening for Pompe disease

Fabry disease

• Hwu WL, Chien YH, Lee NC, Chiang SC, Dobrovolny R, Huang AC, Yeh HY, Chao MC, Lin SJ, Kitagawa T, Desnick RJ, Hsu LW. Newborn screening for Fabry disease in Taiwan reveals a high incidence of the later-onset GLA mutation c.936+919G>A (IVS4+919G>A). Hum Mutat. 2009;30(10):1397-405.
• Chien YH, Olivova P, Zhang XK, Chiang SC, Lee NC, Keutzer J, Hwu WL. Elevation of urinary globotriaosylceramide (GL3) in infants with Fabry disease. Mol Genet Metab.2011;102:57-60.
• Chien YH, Lee NC, Chiang SC, Desnick RJ, Hwu WL. Fabry Disease: Incidence of the Common Later-Onset α-Galactosidase A IVS4+919G>A Mutation in Taiwanese Newborns -- Superiority of DNA-Based to Enzyme-Based Newborn Screening for Common Mutations. Mol Med. 2012;18(1):780-4.
• Chien YH, Bodamer OA, Chiang SC, Mascher H, Hung C, Hwu WL. Lyso-globotriaosylsphingosine (lyso-Gb3) levels in neonates and adults with the Fabry disease later-onset GLA IVS4+919G>A mutation. J Inherit Metab Dis. 2012 Oct 30. [Epub ahead of print]

Severe combined immunodeficiency (SCID)

• Chien YH, Chiang SC, Chang KL, Yu HH, Lee WI, Tsai LP, Hsu LW, Hu MH, Hwu WL. Incidence of severe combined immunodeficiency through newborn screening in a Chinese population. Journal of the Formosan Medical Association. 10.1016/j.jfma.2012.10.020