Biochemical screening of 504,049 newborns in Denmark, the Faroe Islands and Greenland — Experience and development of a routine program for expanded newborn screening

Lund, Allan M.; Hougaard, David M.; Simonsen, Henrik Toft; Andresen, Brage S.; Christensen, Mette; Dunø, Morten; Skogstrand, Kristin; Olsen, Rikke K.J.; Jensen, Ulrich Glümer; Cohen, Arieh; Larsen, Nanna; Saugmann-Jensen, Peter; Gregersen, Niels; Brandt, N. J.; Christensen, Ernst; Skovby, Flemming; Nørgaard‐Pedersen, Bent

doi:10.1016/j.ymgme.2012.06.006

Cited by 62 publications

(107 citation statements)

References 61 publications

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“…Since the introduction of FAOD in the screening panels of NBS programs, generated data has pointed to a significant increase in the disease incidence (Wilcken et al 2007) that is now believed to be about 1:9,000, although some significant differences can be observed between different populations (Zytkovicz et al 2001;Wilcken et al 2003;Frazier et al 2006;Kasper et al 2010;Lindner et al 2011;Lund et al 2012). In the pre-NBS era, diagnosis was achieved mainly through organic acid analysis in the urine of symptomatic patients that resulted in a low detection rate, which together with the detection of potentially asymptomatic patients through NBS, justifies the observed difference (Sturm et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Birth Prevalence of Fatty Acid β-Oxidation Disorders in Iberia

et al. 2014

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Mitochondrial fatty acid b-oxidation disorders (FAOD) are main targets for newborn screening (NBS) programs, which are excellent data sources for accurate estimations of disease birth prevalence. Epidemiological data is of key importance for the understanding of the natural history of the disorders as well as to define more effective public health strategies. In order to estimate FAOD birth prevalence in Iberia, the authors collected data from six NBS programs from Portugal and Spain, encompassing the screening of more than 1.6 million newborns by tandem mass spectrometry (MS/MS), and compared it with available data from other populations. The participating NBS programs are responsible for the screening of about 46% of all Iberian newborns. Data reveals that Iberia has one of the highest FAOD prevalence in Europe (1:7,914) and that Portugal has the highest birth prevalence of FAOD reported so far (1:6,351), strongly influenced by the high prevalence of medium-chain acyl-CoA dehydrogenase deficiency (MCADD; 1:8,380), one of the highest ever reported. This is justified by the fact that more than 90% of Portuguese MCADD patients are of Gypsy origin, a community characterized by a high degree of consanguinity. From the comparative analysis of various populations with comparable data other differences emerge, which points to the existence of significant variations in FAOD prevalences among different populations, but without any clear European variation pattern. Considering that FAOD are one of the justifications for MS/MS NBS, the now estimated birth prevalences stress the need to screen all Iberian newborns for this group of inherited metabolic disorders.

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Section: Introductionmentioning

confidence: 99%

Birth Prevalence of Fatty Acid β-Oxidation Disorders in Iberia

et al. 2014

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“…Carnitine levels in DBS samples from the prospective newborn screening were either analysed as described previously as part of a pilot project of extended newborn screening in babies from 2002 to 2008 or as part of the routine newborn screening from 2009 and onwards (Lund et al 2012). Analyses were done by tandem mass spectrometry using an fC0 cut-off, which from 2002 to 2008 was adjusted when necessary according to medians and percentiles of measured carnitine levels and varied from 5.7 to 6.3 mmol/L, while being 5 mmol/L from 2009.…”

Section: Prospective Newborn Screeningmentioning

confidence: 99%

“…Analyses were done by tandem mass spectrometry using an fC0 cut-off, which from 2002 to 2008 was adjusted when necessary according to medians and percentiles of measured carnitine levels and varied from 5.7 to 6.3 mmol/L, while being 5 mmol/L from 2009. DBS samples for newborn screening were obtained 4-9 days after birth and analysed butylated until 2009 when the recommended time to obtain a sample was changed to 2-3 days after birth and the analysis was done unbutylated, which remains unchanged until today (Lund et al 2012).…”

Section: Prospective Newborn Screeningmentioning

confidence: 99%

“…All DBS samples from children born in the Faroe Islands dating back to 1986 and onwards, which had not previously been analysed for carnitine levels, were also retrospectively analysed unbutylated in order to determine carnitine levels and reveal subjects born with abnormally low levels of carnitine. The stored DBS samples were analysed using tandem mass spectrometry as previously described, but the lower cut-off value for fC0 was set higher at 9 mmol/L to adjust for possible hydrolysis of acylcarnitines to free carnitine known to occur on storage of DBS (Lund et al 2012;Strnadova et al 2007). …”

Section: Prospective Newborn Screeningmentioning

confidence: 99%

“…However, it is not known if newborns with PCD or newborns born to mothers with PCD are affected by abnormally low carnitine levels during foetal development and at birth. Neonatal screening for PCD was routinely implemented in the Faroese newborn screening programme in 2009, but was preceded by a pilot screening study from 2002 to 2009 (Lund et al 2012). The fear that there were undiagnosed PCD patients in the population led to the implementation of a nationwide screening programme in 2009 to uncover as many patients as possible (Rasmussen et al 2014a).…”

Section: Introductionmentioning

confidence: 99%

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Primary Carnitine Deficiency: Is Foetal Development Affected and Can Newborn Screening Be Improved?

Rasmussen¹,

Hougaard

Sandhu

et al. 2017

JIMD Reports

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Primary carnitine deficiency (PCD) causes low levels of carnitine in patients potentially leading to metabolic and cardiac symptoms. Newborn screening for PCD is now routine in many countries by measuring carnitine levels in infants. In this study we report Apgar scores, length and weight in newborns with PCD and newborns born to mothers with PCD compared to controls. Furthermore we report how effective different screening algorithms have been to detect newborns with PCD in the Faroe Islands.Results: Newborns with PCD and newborns born to mothers with PCD did not differ with regard to Apgar scores, length and weight compared to controls. Newborns with PCD and newborns born to mothers with PCD had significantly lower levels of free carnitine (fC0) than controls. Screening algorithms focusing only on fC0 had a high rate of detection of newborns with PCD. Sample collection 4-9 days after birth seems to result in a higher detection rate than the current 2-3 days. Conclusion:The clinical status at birth in infants with PCD and infants born to mothers with PCD does not differ compared to control infants. Screening algorithms for PCD should focus on fC0, and blood samples should be taken when the maternal influence on fC0 has diminished.

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Diagnosis, treatment, management and monitoring of patients with tyrosinaemia type 1: Consensus group recommendations from the German‐speaking countries

Das,

Ballhausen,

Haas

et al. 2024

J of Inher Metab Disea

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Hepatorenal tyrosinaemia (HT1) is an autosomal recessive disorder of tyrosine degradation resulting in hepatic and renal dysfunction, neurological sequelae may occur in some patients. The use of nitisinone (NTBC) has revolutionised treatment and outcome of this disorder. NTBC has to be combined with a low protein diet. While NTBC modulates the disease course in HT1 patients, several issues are open. Optimal dosage, doses per day, therapeutic range of NTBC concentration, mode of protein restriction and biomarkers are not well defined. HCC and neurocognitive deficits are long‐term sequelae. Early diagnosis and treatment are essential to minimise the risk for these complications. Clinical guidance for management of HT1‐patients is required. Randomised clinical studies are difficult in the presence of therapeutic options. We discussed these issues in a consensus group of 10 paediatricians, 1 adult hepatologist, 1 geneticist, 2 dieticians, 2 newborn screening specialists with experience in HT1, 1 psychologist and 2 representatives of a patient group from the German‐speaking countries (DACH). Recommendations were based on scientific literature and expert opinion, also taking into account recent experience with newborn screening. There was strong consensus that newborn screening using succinylacetone (SA) and early treatment are essential for a good outcome. The dose of NTBC should be as low as possible without losing metabolic control. This has to be accompanied by a low protein diet, in some patients a simplified diet without calculation of protein intake. Specific education and psychosocial support are recommended. Indications for liver transplantation were defined. Monitoring shall include clinical findings, levels of SA, tyrosine, phenylalanine and NTBC in (dried) blood.

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Biochemical screening of 504,049 newborns in Denmark, the Faroe Islands and Greenland — Experience and development of a routine program for expanded newborn screening

Cited by 62 publications

References 61 publications

Birth Prevalence of Fatty Acid β-Oxidation Disorders in Iberia

Birth Prevalence of Fatty Acid β-Oxidation Disorders in Iberia

Primary Carnitine Deficiency: Is Foetal Development Affected and Can Newborn Screening Be Improved?

Diagnosis, treatment, management and monitoring of patients with tyrosinaemia type 1: Consensus group recommendations from the German‐speaking countries

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