Introduction of sapropterin dihydrochloride as standard of care in patients with phenylketonuria.

Sapropterin dihydrochloride, a synthetic, stable form of the tetrahydrobiopterin cofactor of phenylalanine hydroxylase, has been shown to reduce plasma phenylalanine (Phe) levels in a significant portion of patients with phenylketonuria (PKU). When we undertook introducing this medication to our PKU clinic population, the challenges of recalling and reconnecting with a variably treated and variably compliant patient population became apparent. We offered a trial of sapropterin to all of our clinic patients with PKU. In order to determine responsiveness, we used a two tier dose escalation protocol. After diet records were taken, and baseline plasma Phe levels were established, a 7-day trial of sapropterin at 10mg/kg/day was started. At day 8, plasma phenylalanine levels were measured. Patients were considered to be responders if they had a 30% reduction in plasma Phe. If they did not respond, the dose of sapropterin was increased to 20 mg/kg/day, and levels were rechecked again in 8 days. Patients who were not responders at this time continued sapropterin for a total of 30 days and had Phe levels checked one last time. Patients who were responders and who were on a Phe-restricted diet underwent gradual liberalization of their diet to the maximum tolerated natural protein intake while still maintaining plasma levels in the acceptable treatment range of 120-360 micromol/L. In our population, 36/39 patients with hyperphenylalaninemia (HPA) who were offered a trial of sapropterin elected to start sapropterin. Five of 36 patients were non-adherent with diet records and/or medication doses and we were unable to determine if they were responders. We were unable to categorize 2 of 31 of the patients who completed the trial as responders due to dietary issues, though they were probably responders. Of the 29 patients who completed the sapropterin trial and we could categorize, 18/29 (62%) were determined to be responders. Patients were classified based on their off-diet diagnostic plasma phenylalanine levels as classical PKU (>1200 micromol/L) and variant PKU (>400 and <1200 micromol/L). The group with variant PKU had a 100% response rate, and patients with classical PKU had a 27% response rate. For the patients in the responder group who were on Phe-restricted diet, we were able to liberalize most diets, in two cases to unrestricted protein intake. We also had unexpected beneficial findings in our clinic experience, including positive behavioral improvements in an adult severely affected by untreated PKU. Even in patients who were not considered to be responders, the introduction of sapropterin provided a tool to reconnect with patients and re-introduce beneficial dietary measures.

Hypoallergenicity and efficacy of an amino acid-based formula in children with cow's milk and multiple food hypersensitivities.

OBJECTIVE: To determine the hypoallergenicity and efficacy of a pediatric amino acid-based formula (AAF), EleCare, for children with cow's milk allergy (CMA) and multiple food allergies (MFA). STUDY DESIGN: Hypoallergenicity was determined by performing blinded oral food challenges in 31 consecutive children with documented CMA. Growth, tolerance, and biochemical response were evaluated during a nonrandomized feeding study with each child serving as his or her own control. RESULTS: Thirty-one children (median age, 23.3 months; range, 6 months to 17.5 years) were recruited; 29 had MFA, 17 had acute reactions and cow's milk-specific IgE antibody, and 14 had allergic eosinophilic gastroenteritis. At study entry, 23 were receiving another AAF; 13 had not tolerated extensively hydrolyzed formula. Eighteen subjects with allergic eosinophilic gastroenteritis and/or MFA were followed up while receiving AAF for a median of 21 months (range, 7 to 40 months), with biochemical analysis performed at 4 months. No statistically significant differences were observed in the change in weight or height National Center for Health Statistics z scores from entry; the percent of expected growth exceeded 90%. There was a small decline in percent eosinophils and increase in hemoglobin, hematocrit, and serum ferritin level (P < .05). Except for small increases in plasma leucine and valine levels (P < or = .006), the remaining biochemical markers were unchanged. CONCLUSIONS: The AAF was hypoallergenic and effective in maintaining normal growth for children with CMA and MFA.

The natural history of peanut allergy.

BACKGROUND: It has traditionally been assumed that peanut allergy is rarely outgrown. OBJECTIVE: The goal of this study was to determine the number of children with peanut allergy who become tolerant of peanut. METHODS: Patients aged 4 to 20 years with a diagnosis of peanut allergy were evaluated by questionnaire, skin testing, and a quantitative antibody fluorescent-enzyme immunoassay. Patients who had been reaction free in the past year and had a peanut IgE (PN-IgE) level less than 20 kilounits of antibody per liter (kU(A)/L) were offered an open or double-blind, placebo-controlled peanut challenge. RESULTS: A total of 223 patients were evaluated, and of those, 85 (PN-IgE < 0.35-20.4 kU(A)/L [median 1.42 kU(A)/L]) participated in an oral peanut challenge. Forty-eight (21.5%) patients had negative challenge results and were believed to have outgrown their peanut allergy (aged 4-17.5 years [median 6 years]; PN-IgE < 0.35-20.4 kU(A)/L [median 0.69 kU(A)/L]). Thirty-seven failed the challenge (aged 4-13 years [median 6.5 years]; RAST < 0.35-18.2 kU(A)/L [median 2.06 kU(A)/L]). Forty-one patients with PN-IgE levels less than 20 kU(A)/L declined to undergo challenge, and 97 were not eligible for challenge because their PN-IgE levels were greater than 20 kU(A)/L or they had had a recent reaction. Sixty-seven percent of patients with PN-IgE levels less than 2 kU(A)/L and 61% with levels less than 5 kU(A)/L had negative challenge results. Of those who underwent challenge, PN-IgE levels for those who passed versus those who failed were different at the time of challenge (P = .009), but not at the time of diagnosis (P = .25). CONCLUSION: This study demonstrates that peanut allergy is outgrown in about 21.5% of patients. Patients with low PN-IgE levels should be offered a peanut challenge in a medical setting to demonstrate whether they can now tolerate peanuts.

Oropharyngeal dysphagia and aspiration in patients with ataxia-telangiectasia.

OBJECTIVES: To determine whether patients with ataxia-telangiectasia exhibit oropharyngeal dysphagia with concomitant aspiration and to examine the relationships among swallowing function, age, and nutritional status. STUDY DESIGN: Seventy patients (mean age, 10.7 years; range, 1.8 to 30 years) had feeding/swallowing and nutritional evaluations. Fifty-one patients, in whom there were concerns about swallowing safety, were examined with a standardized videofluoroscopic swallow study. RESULTS: Fourteen of the 51 patients (27%) with histories suggestive of dysphagia demonstrated aspiration. Of these, silent aspiration (aspiration without a cough) occurred in 10 (71%) patients. Aspirators were significantly older than non-aspirators (mean age, 16.9 vs 10.8 years; P =.002). Advancing age was the strongest factor associated with aspiration during continuous drinking (P =.01). In patients with ataxia-telangiectasia, weight and weight/height were abnormally low at all ages and most compromised in older patients. Patients who aspirated had significantly lower mean weight (P <.002) and weight/height z scores (P <.001) than did patients who did not aspirate. CONCLUSIONS: Oropharyngeal dysphagia is common and appears to be progressive in patients with ataxia-telangiectasia. Older patients also have a higher incidence of poorer nutritional status. The relationship between dysphagia and nutritional status deserves further investigation.

Evaluation of pulmonary function and polysomnography in obese children and adolescents.

Obese adults have an increased prevalence of pulmonary disorders. Although childhood obesity is a common problem, few studies have evaluated the pulmonary complications of obesity in the pediatric population. We, therefore, performed pulmonary function tests (PFTs), polysomnography, and multiple sleep latency tests (MSLTs) in 22 obese children and adolescents [mean age, 10 +/- 5 (SD) years; 73 percent female; 184 +/- 36 percent ideal body weight], none of whom presented because of sleep or respiratory complaints. PFTs were normal in all but two subjects. Ten (46 percent) subjects had abnormal polysomnograms. There was a positive correlation between the degree of obesity and the apnea index (r = 0.47, P < 0.05), and an inverse correlation between the degree of obesity and the Sa0(2) nadir (r = -0.60, P < 0.01). The degree of sleepiness on MSLT correlated with the degree of obesity (r = -0.50, P < 0.05). We conclude that obese children and adolescents have a high prevalence of sleep-disordered breathing, although in many cases it is mild. Obstructive sleep apnea syndrome (OSAS) improved following tonsillectomy and adenoidectomy. We recommend that pediatricians have a high index of suspicion for OSAS when evaluating obese patients, and that polysomnography be considered for these patients.

Determinants of growth in children with the obstructive sleep apnea syndrome.

Failure to thrive is a common complication of childhood obstructive sleep apnea syndrome (OSAS). To further evaluate its cause, we obtained 3-day dietary records, anthropometric measurements, polysomnography, and measurements of energy expenditure during sleep (SEE) in children with OSAS before and after tonsillectomy and adenoidectomy. Fourteen children were studied (mean age, 4 +/- 1 (SD) years). During initial polysomnography, patients had 6 +/- 3 episodes of obstructive apnea/hr, an arterial oxygen saturation nadir of 85% +/- 8%, and peak end-tidal carbon dioxide tension of 52 +/- 6 mm Hg. After surgery, OSAS resolved in all patients. The standard deviation score (z score) for weight increased from -0.30 +/- 1.47 to 0.04 +/- 1.34 (p < 0.005), despite unaltered caloric intake (91 +/- 30 vs 90 +/- 27 kcal/kg per day; not significant). The initial SEE (averaged over all sleep states) was 51 +/- 6 kcal/kg per day; postoperatively, it decreased to 46 +/- 7 kcal/kg per day (p < 0.005). Although SEE decreased during all sleep stages, the greatest decrease occurred during rapid eye movement sleep. The patients with the highest SEE on initial study had the lowest z scores (r = -0.62; p < 0.05). We conclude that SEE decreases and weight improves after resolution of OSAS. We speculate that the poor growth seen in some children with OSAS is secondary to increased caloric expenditure caused by increased work of breathing during sleep.