Elevated phenylalanine on newborn screening: follow-up testing may reveal undiagnosed galactosaemia.

UNLABELLED: Introduction Newborn screening for phenylketonuria (PKU) can reveal other conditions which lead to an increased blood spot phenylalanine (Phe) concentration. We have investigated the proportion of blood spot samples that gave a positive screen due to clinically significant conditions other than PKU, compared the positive predictive value (PPV) of our referral Phe cut-off with that recommended by the UK Newborn Screening Programme Centre (UKNSPC) (>210 and >240 µmol/L, respectively) and evaluated the effectiveness of reflex testing for galactosaemia using a lower blood spot Phe cut-off concentration of 130 µmol/L. METHODS: All blood spot samples that screened positive, for an increased Phe concentration, between April 2001 and March 2008, were identified from the records of the Sheffield Newborn Screening Laboratory and the diagnoses noted. In addition, all cases of galactosaemia detected in or notified to our screening laboratory within this time were also examined and the screened Phe concentrations compared. RESULTS: Out of 438,674 babies who were screened, 67 had Phe concentration >210 µmol/L (15 per 100,000). Of these, 40 had PKU or persistent hyperphenylalaninaemia with a Phe concentration identified by screening between 270 and 2350 µmol/L. A further 11 were diagnosed with another clinically significant disorder: galactosaemia (n = 8), biopterin defects (n = 2), tyrosinaemia Type 1 (n = 1). In addition, 16 had transient elevations in Phe. In total, nine cases of galactosaemia were identified, of whom, three had Phe concentrations <240 µmol/L with one asymptomatic individual having a concentration <210 µmol/L. CONCLUSIONS: Adoption of the UKNSPC recommended cut-off (>240 µmol/L) will not affect the detection rate of classical PKU, but will improve the PPV from 76% to 80%. The use of a lower cut-off (130 µmol/L) for reflex galactosaemia testing enables the timely identification of asymptomatic cases that benefit particularly from early treatment, without prompting any unnecessary clinical referrals or delaying any referrals. This intervention may reduce mortality in this vulnerable group.

Mucosal immune responses to capsular pneumococcal polysaccharides in immunized preschool children and controls with similar nasal pneumococcal colonization rates.

BACKGROUND: Immunization with conjugate pneumococcal vaccines induces significant primary and memory IgG anti-polysaccharide (PS) responses in serum. It can also induce mucosal responses in infants especially after a polysaccharide booster. However, it is unclear whether it can prime for mucosal memory responses on nasal exposure to pneumococcus, which may be important in protection against pneumococcal invasion and/or carriage. METHOD: IgA and IgG to serotypes 4, 6B, 9V, 14, 18C, 19F and 23F (conjugate vaccine serotypes), 1 and 3 (nonvaccine serotypes) capsular PS were measured by immunoassay in saliva from 2- to 5-year-old children previously given three doses of 7-valent pneumococcal conjugate vaccine in infancy, followed by 23-valent PS vaccine at 13 months and from unvaccinated controls of similar age and sex. Salivary antibody responses were analyzed in relation to carriage of pneumococci assessed by bacterial culture of nasopharyngeal swab samples collected in the summer and winter of the year 2000. RESULTS: Rates of detectable IgG antibodies to all vaccine serotypes except 23F were higher in subjects than in controls. No such differences were observed for IgA antibodies except for serotype 6B. Nasal colonization rates were similar, and in both groups mucosal IgA responses were more common and larger than IgG responses. CONCLUSIONS: The mucosal anti-capsular IgA responses observed could develop in response to colonization in preschool children, regardless of vaccination status, and contribute to the falling carriage rates observed with increasing age.

Mucosal immune responses to meningococcal conjugate polysaccharide vaccines in infants.

BACKGROUND: Serogroup C meningococcal conjugate polysaccharide vaccines have been reported to induce significant serum IgG antibodies and immunologic memory in infants. Because meningococcus is a mucosal pathogen colonizing the nasopharynx, local mucosal immune responses may play an important role in host defense against infection and carriage. We have investigated the mucosal IgA and IgG antibody responses to two meningococcal C conjugate vaccines in the saliva of healthy infants. METHODS: Specific salivary IgA and IgG antibodies to two meningococcal C polysaccharide conjugate vaccines (Menjugate from Chiron Corp., n = 46; and Meningitec from Wyeth Lederle, n = 54) were investigated by immunoassay in infants after parenteral vaccinations at the ages of 2, 3 and 4 months. Unstimulated saliva samples were collected immediately before the first immunization and 1 month after the third immunizations. Forty healthy infants receiving the same routine vaccines but no meningococcal C vaccine were recruited as controls. RESULTS: There were significant increases in meningococcal C polysaccharide-specific IgG antibody concentrations postvaccination compared with prevaccination concentrations in both vaccinated groups (both P < 0.001), but no change in the control group. There were no significant increases in specific IgA postvaccination geometric mean concentrations in either the vaccine or the control groups. The number of IgA positives postvaccination increased slightly in the Wyeth vaccine group vs. controls (P < 0.05). CONCLUSIONS: Significant salivary IgG antibodies to meningococcal C polysaccharide were observed after parenteral immunization with two meningococcal C conjugate vaccines, whereas there was no significant increase in specific IgA antibody levels for these two vaccines.