Clinical severity and quality of life in children and adolescents with Rett syndrome.

OBJECTIVE: The clinical features and genetics of Rett syndrome (RTT) have been well studied, but examination of quality of life (QOL) is limited. This study describes the impact of clinical severity on QOL among female children and adolescents with classic RTT. METHODS: Cross-sectional and longitudinal analyses were conducted on data collected from an NIH-sponsored RTT natural history study. More than 200 participants from 5 to 18 years of age with classic RTT finished their 2-year follow-up at the time of analysis. Regression models after adjustment for their MECP2 mutation type and age at enrollment were used to examine the association between clinical status and QOL. RESULTS: Severe clinical impairment was highly associated with poor physical QOL, but worse motor function and earlier age at onset of RTT stereotypies were associated with better psychosocial QOL; conversely, better motor function was associated with poorer psychosocial QOL. CONCLUSIONS: Standard psychosocial QOL assessment for children and adolescents with RTT differs significantly with regard to their motor function severity. As clinical trials in RTT emerge, the Child Health Questionnaire 50 may represent one of the important outcome measures.

Epilepsy and the natural history of Rett syndrome.

BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder primarily seen in females, most with a mutation in MECP2. Epilepsy has been reported in 50%-80%. Previous reports were based on small sample sizes or parent-completed questionnaires, or failed to consider the impact of specific MECP2 mutations. METHODS: The Rare Disease Consortium Research Network for RTT is an NIH-funded project to characterize the clinical spectrum and natural history of RTT in advance of clinical trials. Evaluations include clinical status (classic vs atypical RTT), MECP2 mutations, clinical severity, and presence, frequency, and treatment of seizures. RESULTS: Enrollment as of June 2008 is 602; 528 (88%) meet clinical criteria for classic RTT. Of these, 493 (93%) have MECP2 mutations. Age range was 8 months to 64 years. A total of 360 (60%) were reported to have seizures, including 315 (60%) classic and 45 (61%) atypical RTT. Physician assessment of the 602 indicated that 48% had seizures. There was no significant difference in seizure occurrence by race/ethnicity. A significant age impact for seizures was seen and seizures were infrequent before age 2 years. MECP2 mutations most frequently associated with epilepsy were T158M (74%) and R106W (78%), and less frequently R255X and R306C (both 49%). Individuals with seizures had greater overall clinical severity, and greater impairment of ambulation, hand use, and communication. DISCUSSION: Seizures are common in Rett syndrome, have an age-related onset and occurrence, vary by mutation, and are associated with greater clinical severity. This information represents a key consideration for designing clinical trials.

Nutrition support for pediatric patients with inflammatory bowel disease: a clinical report of the North American Society for Pediatric Gastroenterology, Hepatology And Nutrition.

Impairment of growth and malnutrition are significant complications of inflammatory bowel disease (IBD) in pediatric patients. Since this topic was last reviewed in these pages (), a number of studies have further explored the epidemiology and pathogenesis of these nutritional complications of IBD in an effort to provide more effective interventions to prevent the long-term consequences of chronic nutrient deficiencies in childhood. In addition, during the past 15 years, the use of selected nutrients and microorganisms (probiotics) as primary or adjunctive therapy for the treatment of IBD has become an emerging area of great interest. The following is a Clinical Report from the Nutrition and Inflammatory Bowel Disease Committees of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

Z score prediction model for assessment of bone mineral content in pediatric diseases.

The objective of this study was to develop an anthropometry-based prediction model for the assessment of bone mineral content (BMC) in children. Dual-energy X-ray absorptiometry (DXA) was used to measure whole-body BMC in a heterogeneous cohort of 982 healthy children, aged 5-18 years, from three ethnic groups (407 European- American [EA], 285 black, and 290 Mexican-American [MA]). The best model was based on log transformations of BMC and height, adjusted for age, gender, and ethnicity. The mean +/- SD for the measured/predicted in ratio was 1.000 +/- 0.017 for the calibration population. The model was verified in a second independent group of 588 healthy children (measured/predicted In ratio = 1.000 +/- 0.018). For clinical use, the ratio values were converted to a standardized Z score scale. The whole-body BMC status of 106 children with various diseases (42 cystic fibrosis [CF], 29 juvenile dermatomyositis [JDM], 15 liver disease [LD], 6 Rett syndrome [RS], and 14 human immunodeficiency virus [HIV]) was evaluated. Thirty-nine patients had Z scores less than -1.5, which suggest low bone mineral mass. Furthermore, 22 of these patients had severe abnormalities as indicated by Z scores less than -2.5. These preliminary findings indicate that the prediction model should prove useful in determining potential bone mineral deficits in individual pediatric patients.

Infant feeding: a critical look at infant formulas.

Commercially available infant formulas serve as the best alternative to human milk when breastfeeding is not possible. Infant formulas are designed specifically to mimic the composition of human milk or the functional aspects of human milk feeding. This review highlights the issues related to the composition of infant formulas. The most hotly debated issue currently is whether to add long-chain polyunsaturated fatty acids to infant formulas. Other controversial topics include the safety and efficacy of soy-based protein formulas, protein quantity and quality as they relate to the infant's nutritional needs and feeding tolerance, and the replacement of lactose with other carbohydrate sources for specialized infant formulas. Recent modifications in the fat blend of infant formulas have led to improved fat digestibility. However, the full spectrum of benefits associated with the addition of nucleotides awaits further study. Modifications to infant formulas are made when the preponderance of scientific evidence suggests that the compositional change will better meet the nutritional needs of the infant.

Influence of mutation type and X chromosome inactivation on Rett syndrome phenotypes.

We screened 71 sporadic and 7 familial Rett syndrome (RTT) patients for MECP2 mutations by direct sequencing and determined the pattern of X chromosome inactivation (XCI) in 39 RTT patients. We identified 23 different disease-causing MECP2 mutations in 54 of 71 (76%) sporadic patients and in 2 of 7 (29%) familial cases. We compared electrophysiological findings, cerebrospinal fluid neurochemistry, and 13 clinical characteristics between patients carrying missense mutations and those carrying truncating mutations. Thirty-one of 34 patients (91%) with classic RTT had random XCI. Nonrandom XCI was associated with milder phenotypes, including a mitigated classic RTT caused by a rare early truncating mutation. Patients with truncating mutations have a higher incidence of awake respiratory dysfunction and lower levels of cerebrospinal fluid homovanillic acid. Scoliosis is more common in patients with missense mutations. These data indicate that different MECP2 mutations have similar phenotypic consequences, and random XCI plays an important role in producing the full phenotypic spectrum of classic RTT. The association of early truncating mutations with nonrandom XCI, along with the fact that chimeric mice lacking methyl-CpG-binding protein 2 (MeCP2) function die during embryogenesis, supports the notion that RTT is caused by partial loss of MeCP2 function.

Oropharyngeal dysfunction and gastroesophageal dysmotility are present in girls and women with Rett syndrome.

BACKGROUND: Feeding impairment frequently complicates the course of children with neurologic disorders and places them at risk for malnutrition and growth failure. Although feeding abnormalities have been reported in female patients with Rett syndrome, the mechanisms that account for these findings have not been elucidated fully. This study was designed to characterize the clinical features of oropharyngeal and gastroesophageal dysfunction and their impact on the dietary intake and nutritional status of female subjects with Rett syndrome. METHODS: The clinical features of oropharyngeal and gastroesophageal dysfunction in 13 female patients with Rett syndrome, (age range, 3.7 to 25.7 years) were characterized by an oral feeding assessment, swallowing function study, and upper gastrointestinal series. Growth, nutritional status, and body composition were determined by stadiometry and anthropometry. Dietary intakes were determined from 3-day food records. RESULTS: Oropharyngeal dysfunction and gastroesophageal dysmotility were present in 100% and 69%, respectively, of the study patients with Rett syndrome. The scope and severity of these abnormalities were apparent only by videofluoroscopy. Abnormalities of oropharyngeal function included poor tongue mobility, reduced oropharyngeal clearance, and laryngeal penetration of liquids and solid food during swallowing. Esophageal dysmotility included absent primary or secondary waves, delayed emptying, atony, the presence of tertiary waves, spasm, and gastroesophageal reflux. Gastric dysmotility included diminished peristalsis or atony. Lower dietary energy intakes were associated with persistence of residue in the valleculae and pyriform sinuses and less body fat. CONCLUSION: The prevalence of oropharyngeal dysfunction and gastroesophageal dysmotility warrants early diagnostic evaluation and intervention strategies to improve the nutritional status of girls and women with RS.

Organ growth in Rett syndrome: a postmortem examination analysis.

Rett syndrome is a disorder of unknown etiology in females that manifests as severe mental and motor retardation during the first years of life. A postnatal pattern of altered growth is its earliest clinical expression. Head growth decelerates during the first year of age and is followed by a decline in somatic (height/weight) growth. The decreased occipitofrontal circumference (OFC) is reflected in decreased brain size, and measurements of the dendrites of cortical neurons suggest that a developmental and growth arrest have occurred. To further document growth in Rett syndrome, measurements of organ weights, as recorded in 39 postmortem examination studies were compared with normal organ weights for females of comparable age and height. These organ weights suggest that the pattern of growth failure in Rett syndrome, as compared with other forms of mental handicap, such as Down syndrome and Turner's syndrome, may be unique. In Rett syndrome the rate of brain growth, as derived from OFC, decelerates after birth. The increment in normal brain weight after 4 years of age, the age of the first postmortem examinations, is not observed in the Rett brain. The heart, kidneys, liver, and spleen grow at the normally defined rate until 8-12 years of age, when their growth rate decelerates, but their growth continues achieving organ weights that are appropriate for the height of the female. Adrenal weights are normal. These observations suggest that despite a generalized decreased growth in Rett syndrome the brain may be preferentially affected in this syndrome.

Increased energy expenditure associated with repetitive involuntary movement does not contribute to growth failure in girls with Rett syndrome.

OBJECTIVE: To determine whether increased total daily energy expenditure (TDEE) associated with repetitive, involuntary movements contributes to growth failure in girls with Rett syndrome (RS). STUDY DESIGN: Fourteen girls with RS and 11 healthy girls were studied for 10 days to obtain measurements of height, weight, body circumference, and skin-fold thickness with stadiometric and anthropometric methods; whole-body potassium by potassium 40 counting; 72-hour dietary energy intakes by test weighing; 24-hour activity patterns using observational methods; and TDEE using the doubly-labeled water technique. RESULTS: TDEE, when adjusted for differences in lean body mass, did not differ significantly between girls with RS and healthy girls. Although girls with RS spent more waking hours in physical activity than their healthy counterparts (85%+/-10% vs. 73%+/-11% awake time per day, p < 0.05), their repetitive movements were not sufficiently intense to increase TDEE. However, girls with RS had significantly less lean body mass, but not body fat, which contributed to their lower absolute TDEE in comparison with that of healthy girls (845+/-251 vs. 1453+/-534 kcal/day, p < 0.01). Dietary energy intake, when adjusted for differences in body weight, was not significantly different in girls with RS compared with healthy girls. CONCLUSIONS: Increased TDEE as a result of repetitive, involuntary movements does not explain the alterations in growth and body composition of girls with RS.

Lean body mass of well-nourished women is preserved during lactation.

To determine whether the lean body mass of well-nourished women was mobilized to support milk protein output during lactation, the body composition of 10 lactating and 10 nonlactating women was examined longitudinally at 6-wk intervals between 6 and 24 wk postpartum and at 52 wk postpartum, and that of 10 nulliparous women was examined at equivalent intervals, by using clinical anthropometry and whole-body potassium counting. Milk production was determined at 6-wk intervals during the period of exclusive breast-feeding (6-24 wk postpartum) by the test-weighing procedure. Milk composition was determined by chemical analysis. Dietary intakes were determined at 6-wk intervals between 6 and 24 wk postpartum from 3-d food records with use of a nutrient database. Lean body mass was maintained in women who exclusively breast-fed their infants during the first 6 mo postpartum while consuming dietary protein in amounts that exceeded those of their nonlactating counterparts by 55%. The high protein intakes were sustained throughout lactation despite a progressive reduction by 32% of milk protein output. Lean body mass was preserved throughout lactation in well-nourished women, suggesting that the metabolic needs of milk protein production were met solely by higher protein intakes of the lactating women.

Sensitive measures of nutritional status in children in hospital and in the field.

Protein-energy malnutrition and obesity are the most common nutritional disorders that complicate the clinical course of children with neoplastic diseases. Sensitive measures of nutritional status should be used to detect these problems in children with cancer. Height and weight measurements are the mainstay of the nutritional assessment of the child. These measurements can be converted to growth velocities or to height-for-age and weight-for-height Z-scores or percent of expected values to provide a measure of the degree of under- or over-nutrition in the child. Skinfold thickness and circumference measurements of the arms, legs and/or trunk may be useful to characterize the changes in peripheral fat depots and muscle mass, respectively. However, the assessments of body composition using these measurements are subject to methodological error because selected skinfold sites are excluded. Whole-body potassium, measured by 40K counting, and total body water, measured by deuterium or 18O dilution, serve as "gold standards" to determine the lean body mass and body fat status of the child, but these techniques may not be practical in all settings. The assessment of the nutritional status of the child serves as a guide to early nutritional intervention. Indicators for early nutritional intervention include: (1) height-for-age and weight-for-height or -age Z-scores more than 2 SD below the mean for age, (2) height-for-age measurements less than 95% of expected, (3) weight-for-height measurements less than 90% or greater than 120% of expected and (4) height velocities less than 5 cm/year after 2 years of age. Early nutritional intervention is essential to restore normal body composition, reverse linear growth arrest, promote tolerance to chemotherapeutic and radiation regimens and improve the quality of life in children with cancer.

Lactational performance of adolescent mothers shows preliminary differences from that of adult women.

PURPOSE: The purposes of this study were to characterize milk production, milk composition, and the lactational behavior of adolescent mothers, and to compare their lactational performance with that of adult females. METHODS: Twenty-two lactating mothers, 11 adolescents and 11 adults, were studied at 6-week intervals between 6 and 24 weeks postpartum. Milk production was determined by the test-weighing procedure. Milk nutrient composition was determined by standard chemical analyses. Frequency and duration of nursing and the use of supplemental formula and complementary foods were recorded. RESULTS: The amount of milk adolescents produced at 6, 12, 18, and 24 weeks postpartum ranged from 37-54% less (P < .05) than that of the adults and resulted in a 45% weaning rate at 18 weeks postpartum in the younger group. Milk nutrient concentrations were not significantly different between groups, with the exception of significantly higher sodium concentrations during early lactation in the adolescents' milk. Lactational behavior differed significantly between the adolescent and adult groups; however, with the exception of the lower frequency of daytime nursing and the tendency toward the early introduction of supplemental formula in the adolescent group, these behavioral differences were the result of the racial and ethnic differences between the two groups. The differences in lactational behavior did not contribute to the differences in milk production between the adolescents and adult mothers. CONCLUSIONS: This preliminary study suggests that milk production was reduced in adolescent mothers compared with adult females. Although behavioral strategies that increase the frequency of daytime nursing and reduce the frequency of supplemental feedings may enhance the milk production of adolescent mothers, other biological factors may account for their poorer lactational performance.

PIP: In a comparative study of the lactational performance of 11 adolescent and 11 adult breast-feeding mothers from the US, adolescents were found to produce significantly less milk and lactate for a significantly shorter period of time than their adult counterparts. All subjects were assessed at 6-24 weeks postpartum. The adolescents produced 37% and 54% less milk at 6 and 24 weeks postpartum, respectively, than adult women. These differences in milk production were significant even when adjusted for differences in the frequency and duration of breast feeding episodes and use of supplementary feeds. The amount of dietary energy the infants of adolescents received from human milk alone was clearly inadequate, at every time point, to support normal growth rates. In both groups, the average frequency of nursing episodes during the first 12 weeks postpartum was 7 or more per 24 hours (consistent with current recommendations for adequate lactation); adolescents, however, spent significantly less time nursing and provided greater quantities of supplementary feeds. While all adult women breast-fed throughout the study period, 20% of adolescents had stopped breast feeding by 12 weeks, 50% weaned by 18 weeks, and 64% had discontinued breast feeding by 24 weeks. Unexpectedly, the energy, lactose, fat, total nitrogen, protein nitrogen, nonprotein nitrogen, sodium, potassium, calcium, and phosphorous concentrations showed little difference between the two age groups. The absence of data from the first 6 weeks of life makes it impossible to rule out a role for early formula supplementation in the decreased milk production of adolescents. It is believed,however, that adolescents may be biologically incapable of producing a full complement of milk because of their developmental immaturity.

Human milk protein does not limit growth of breast-fed infants.

BACKGROUND: The efficiency with which breast- and formula-fed infants utilize dietary nutrients is likely to provide insight into their relative requirements for the growth process. METHODS: We measured longitudinal changes in growth, body composition, and dietary intakes in breast- and formula-fed infants and estimated the gross efficiency with which dietary nitrogen and energy were used for lean body mass and body fat deposition. Lean body mass and body fat were determined in 10 breast-fed and 10 formula-fed infants at 6-week intervals during the first 24 weeks of life by the 18O dilution technique. Dietary nitrogen and energy intakes were determined from the amount of milk and food consumed and the nutrient content of the feedings. The gross efficiency of nutrient utilization was calculated for each infant from the cumulative dietary intake and the change in body composition with time. RESULTS: Length and weight gains and lean body mass and body fat accretion during the first 24 weeks of life were similar between breast- and formula-fed infants despite significantly higher nitrogen and energy intakes of the formula-fed group. The gross efficiency of dietary nitrogen utilization for lean body mass deposition was almost two-fold lower in formula- than in breast-fed infants, whereas the efficiency of dietary energy utilization for lean body mass and body fat deposition was similar between groups. Despite apparent differences in the efficiency of nitrogen utilization, there was no association between lean body mass deposition and dietary protein intake, implying that human milk protein does not limit growth quantitatively in breast-fed infants. CONCLUSIONS: These differences in nutrient utilization illustrate the biologic adaptability of human infants who are equipped with mechanisms that promote normal growth despite the variability of their nutrient intake.

Whole-body protein turnover in the fed state is reduced in response to dietary protein restriction in lactating women.

We examined the adaptive responses of body protein metabolism in the fed state to dietary protein restriction in lactating women to determine whether rates of body protein degradation and synthesis were lower than those of nonlactating women. Thirteen healthy women (five lactating, four nonlactating postpartum, four nulliparous) aged 28-32 y were given protein intakes of 1.5, 0.4, and 1.0 g.kg-1.d-1 over three consecutive 3-d periods, respectively. At the end of each period, while in the fed state, subjects received orally a single bolus dose of [1-13C]leucine. A 24-h urine collection was obtained simultaneously. Whole-body protein metabolism was characterized by using the end product model based on nitrogen excretion and leucine catabolism. Nitrogen flux and rates of protein degradation and synthesis in the fed state were significantly lower at a dietary protein intake of 1.0 g.kg-1.d-1 in lactating women than in their nonlactating postpartum counterparts. Net protein retention in the fed state was significantly higher at a dietary protein intake of 1.0 g.kg-1.d-1 in lactating than in nonlactatating postpartum and nulliparous women because of the relatively greater reduction in protein degradation than in protein synthesis. These studies suggest that lactating women rapidly adapt to dietary protein restriction by down-regulating protein metabolism, and that 13C-labeled amino acid tracers in combination with urinary nitrogen excretion serve as useful metabolic markers for the adequacy of the dietary protein content of lactating women.

Marginal dietary protein restriction reduced nonprotein nitrogen, but not protein nitrogen, components of human milk.

OBJECTIVE: This study was designed to determine whether marginal dietary protein intakes of lactating women alter their milk production and composition. The study followed the observation that marginal dietary protein intakes lead to significantly negative nitrogen balances in these women. METHODS: Twenty-four healthy, mature lactating women were divided evenly into three groups on the basis of postpartum times; 1, 5, or 12 months. Each woman was given a controlled protein diet of either 1.5 (HP) or 1.0 (MP) g/kg body weight/day for 7 to 10 days. Milk production was measured for 72 hours by test weighing the infant before and after feeding. Milk samples from alternate breasts were collected for 24 hours, pooled, and analyzed for their protein nitrogen, nonprotein nitrogen, free and protein-bound amino acid, and lactoferrin concentrations. RESULTS: Reduced dietary protein intakes were associated with a decrease (p < 0.05) in the nonprotein nitrogen and total free amino acid fractions of milk. Although urea was unaffected, the concentrations of milk free leucine, phenylalanine, histidine, and ornithine were lower (p < 0.05) in the MP than in the HP group, while the output of leucine and histidine tended to be lower in the MP group. The amount of milk produced, as well as the amounts of protein nitrogen, protein-bound amino acid, and lactoferrin and their concentrations were unaffected by a reduction of dietary protein. CONCLUSIONS: Maternal milk production and the protein nitrogen, but not the nonprotein nitrogen, fraction of human milk were relatively well-preserved in the presence of a short-term, marginal reduction of dietary protein.

Insulin, cortisol and thyroid hormones modulate maternal protein status and milk production and composition in humans.

The partitioning of dietary and endogenous nutrients during lactation is not well understood. To examine associations between plasma hormone and substrate profiles and indices of either maternal body protein metabolism or lactational performance, we measured plasma insulin, cortisol, prolactin, thyroxine, triiodothyronine, individual amino acid, blood urea nitrogen, and prealbumin concentrations in lactating and nulliparous women in the postabsorptive state. We related these measurements to the subjects' nitrogen balance, urinary 3-methylhistidine excretion, [1-13C]leucine metabolism and milk production. Insulin concentrations showed significant positive relationships with nitrogen balance and prealbumin concentrations; cortisol levels showed a significant negative relationship with nitrogen balance and a significant positive relationship with leucine incorporation into protein. Thyroid hormone concentrations showed significant positive relationships with urinary 3-methylhistidine excretion, leucine incorporation into protein, and milk production. Proline concentrations were associated positively with nitrogen balance and negatively with leucine incorporation into protein, whereas glutamate-glutamine concentrations showed positive associations with leucine oxidation and milk nitrogen concentrations. We propose that insulin and cortisol modulate the channeling of nutrients between anabolic and anti-anabolic aspects of maternal body protein metabolism, whereas thyroid hormones and cortisol modulate nutrient partitioning toward milk production and visceral protein synthesis. We suggest that some nonessential amino acids (proline, glutamate-glutamine) may become limiting during lactation because of their unique contributions to milk protein synthesis.

Altered energy balance may account for growth failure in Rett syndrome.

To determine whether alterations in energy balance account for growth failure in Rett syndrome, we measured dietary energy intakes, fecal fat losses, activity patterns, and sleeping as well as quietly and actively awake metabolic rates in Rett syndrome girls and healthy controls. Dietary energy intakes and fecal fat losses did not differ between the groups. Metabolic rates while sleeping and quietly awake were 23% lower (P < .05) in Rett syndrome girls than in controls; metabolic rates while actively awake did not differ between the groups. However, because of the 2.4-fold greater time (P < .001) spent in involuntary motor movement, energy expenditure associated with activity was twofold greater (P < .05) in Rett syndrome girls than in controls. Although total daily energy expenditure of the two groups did not differ significantly, energy balance was less positive in the Rett syndrome girls than in the controls. This small difference in energy balance, if sustained over months to years, is sufficient to account for growth failure in Rett syndrome girls.

Case report: failure to thrive in a breast-fed infant is associated with maternal dietary protein and energy restriction.

OBJECTIVE: To determine whether failure to thrive in a breast-fed infant could be attributed to altered milk production or composition from a mother who consumed a self-imposed energy- and protein-restricted diet. DESIGN: We evaluated the changes in growth and body composition, dietary intakes, and milk production and composition in a mother-infant pair throughout the first postpartum year. SETTING: The Children's Nutrition Research Center Metabolic Research Unit. SUBJECTS: A breast-feeding mother-infant pair. MEASURES OF OUTCOME: Body composition was measured by total body electrical conductance, dietary intakes by food records, milk production by the test weighing procedure, and milk composition by proximate analyses. RESULTS: A marked decline in the infant's linear and ponderal growth rates occurred when the mother consumed an energy- (20 kcal.kg-1.d-1) and protein- (0.7 g.kg-1.d-1) restricted diet. The retardation in body weight gain was associated with an arrest of body fat, but not lean body mass, accretion. Maternal milk production showed positive relationships with maternal dietary energy (p < 0.01, r = 0.93) and protein (p < 0.05, r = 0.83) intakes. Milk composition reflected changes consistent with those of weaning rather than a sequela of the mother's diet. CONCLUSIONS: We concluded that failure to thrive in a breast-fed infant could be attributed to reduced milk production in conjunction with maternal dietary energy- and protein-restriction and that an assessment of maternal dietary intakes is essential in an evaluation of the breast-fed infant with failure to thrive.

Leucine oxidation changes rapidly after dietary protein intake is altered in adult women but lysine flux is unchanged as is lysine incorporation into VLDL-apolipoprotein B-100.

We measured the 13C enrichments of expired CO2 and deuterium enrichments of plasma free lysine and VLDL-apolipoprotein B-100 in five nulliparous women who received an oral bolus dose of [1-13C]leucine and a primed, constant infusion of [2H4]lysine on d 2 and 6 while consuming protein diets of 1.5, 1.0 and 0.4 g.kg-1 x d-1. Peak enrichments and cumulative percent recoveries of 13C in expired CO2 increased during the high, and decreased during the low protein periods within 24 h of altered intakes; these changes averaged 89% of that on d 6 of the high and low protein diets. The early changes in leucine oxidation showed significant relationships with urinary nitrogen excretion on d 6 of the dietary periods. The ratio of the isotopic enrichment of lysine in VLDL-apolipoprotein B-100 to that in plasma was unaltered by the level of protein intake. Thus, amino acid oxidation adapts rapidly to altered protein intakes in adult women and is useful to determine protein needs during rapidly changing physiologic conditions. However, 6-d periods of protein intake over the range of 1.5 to 0.4 g.kg-1 x d-1 do not affect the proportional use of dietary amino acids for hepatic secretory protein synthesis.