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Published on: June 25, 2010
Newborn screening for homocystinuria: Irish and world experience
E R Naughten1, S Yap, P D Mayne
1The Metabolic Unit, The Children's Hospital, Dublin, Ireland.
Insights
Newborn screening for homocystinuria (HCU) using bacterial inhibition assays has a history of discontinuation. Factors like breast-feeding and pyridoxine responsiveness can lead to missed cases in screening programs.
Area of Science:
- Biochemistry
- Genetics
- Public Health
Background:
- Newborn screening for cystathionine beta-synthase deficiency (homocystinuria; HCU) began in the late 1960s.
- Seven countries utilize HCU screening, while 12 have discontinued programs.
- Worldwide HCU incidence varies significantly, from 1:65,000 in Ireland to 1:900,000 in Japan.
Purpose of the Study:
- To evaluate the effectiveness and identify limitations of newborn screening for homocystinuria (HCU).
- To analyze factors contributing to missed cases in HCU screening programs.
Main Methods:
- Review of historical newborn screening methodologies for HCU, including bacterial inhibition assay (BIA), amino acid chromatography, and tandem mass spectrometry.
- Analysis of data from HCU screening programs, particularly the Irish program, to assess detection rates and identify missed cases.
- Comparison of findings with results from five other international screening programs.
Main Results:
- The bacterial inhibition assay (BIA) is a common but variable method for HCU screening, with differing methionine cut-off concentrations.
- In Ireland, 21 out of 25 HCU cases were detected via newborn screening; four cases were missed.
- Missed cases were associated with breast-feeding, pyridoxine responsiveness, early hospital discharge, low protein intake, and high methionine cut-off values.
Conclusions:
- Newborn screening for HCU has limitations, with approximately one in five cases potentially missed by current programs.
- Factors such as infant feeding practices and genetic variability (pyridoxine responsiveness) impact screening accuracy.
- Optimizing screening protocols and considering these factors are crucial for improving HCU detection rates.
Abstract:
Newborn screening for cystathionine beta-synthase deficiency (homocystinuria; HCU) was started in the late 1960s using a bacterial inhibition assay (BIA). At least seven countries have either national or regional screening programmes; 12 programmes are known to have discontinued. The worldwide incidence of HCU is approximately 1 in 335,000 but varies from 1:65,000 (Ireland) to 1:900,000 (Japan). Methodologies include the BIA, one-dimensional or thin-layer amino acid chromatography and, more recently, tandem mass spectrometry. The BIA diagnostic cut off concentration of blood methionine varies from 67 to 270 micromol/ (10-40 mg/l) with a median of 135 micromol/l (20 mg/l). In Ireland, 25 cases of HCU from 19 families have been identified from 1.58 million newborn infants since 1971; 21 cases were detected through the screening programme. Of the four missed cases, three were breast-fed at the time of blood collection and one was pyridoxine responsive. These findings were in broad agreement with the results from five other programmes, in which approximately one in every five cases was missed by the screening programme. Early hospital discharge, low protein intake, high blood methionine cut-off concentration and pyridoxine responsiveness were all identified as contributing to missed cases.
