Plasma methylcitric acid and its correlations with other disease biomarkers: The impact in the follow up of patients with propionic and methylmalonic acidemia.

Methylcitric acid (MCA) analysis has been mainly utilized for the diagnosis of propionate disorders or as a second-tier test in newborn screening, but its utility for patients monitoring still needs to be established. We explored the potential contribution of MCA in the long-term management of organic acidurias. We prospectively evaluated plasma MCA and its relationship with disease biomarkers, clinical status, and disease burden in 22 patients, 13 with propionic acidemia (PA) and nine with methylmalonic acidemia (MMA) on standard treatment and/or after transplantation. Samples were collected at scheduled routine controls or during episodes of metabolic decompensation (MD), 10 patients were evaluated after transplantation (six liver, two combined liver and kidney, 2 kidney). MCA levels were higher in PA compared to MMA and its levels were not influenced by the clinical status (MD vs well state). In MMA, MCA was higher in elder patients and, along with fibroblast growth factor 21 (FGF21) and plasma methylmalonic acid, negatively correlated with GFR. In both diseases, MCA correlated with ammonia, glycine, lysine, C3, and the C3/C2, C3/C16 ratios. The disease burden showed a direct correlation with MCA and FGF21, for both diseases. All transplanted patients showed a significant reduction of MCA in comparison to baseline values, with some differences dependent on the type of transplantation. Our study provided new insights in understanding the disease pathophysiology, showing similarities between MCA and FGF21 in predicting disease burden, long-term complications and in evaluating the impact of organ transplantation.

Dietary practices in methylmalonic acidaemia: a European survey.

Background The dietary management of methylmalonic acidaemia (MMA) is a low-protein diet providing sufficient energy to avoid catabolism and to limit production of methylmalonic acid. The goal is to achieve normal growth, good nutritional status and the maintenance of metabolic stability. Aim To describe the dietary management of patients with MMA across Europe. Methods A cross-sectional questionnaire was sent to European colleagues managing inherited metabolic disorders (IMDs) (n=53) with 27 questions about the nutritional management of organic acidaemias. Data were analysed by different age ranges (0-6 months; 7-12 months; 1-10 years; 11-16 years; >16 years). Results Questionnaires were returned from 53 centres. Twenty-five centres cared for 80 patients with MMA vitamin B12 responsive (MMAB12r) and 43 centres managed 215 patients with MMA vitamin B12 non-responsive (MMAB12nr). For MMAB12r patients, 44% of centres (n=11/25) prescribed natural protein below the World Health Organization/Food and Agriculture Organization/United Nations University (WHO/FAO/UNU) 2007 safe levels of protein intake in at least one age range. Precursor-free amino acids (PFAA) were prescribed by 40% of centres (10/25) caring for 36% (29/80) of all the patients. For MMAB12nr patients, 72% of centres (n=31/43) prescribed natural protein below the safe levels of protein intake (WHO/FAO/UNU 2007) in at least one age range. PFAA were prescribed by 77% of centres (n=33/43) managing 81% (n=174/215) of patients. In MMAB12nr patients, 90 (42%) required tube feeding: 25 via a nasogastric tube and 65 via a gastrostomy. Conclusions A high percentage of centres used PFAA in MMA patients together with a protein prescription that provided less than the safe levels of natural protein intake. However, there was inconsistent practices across Europe. Long-term efficacy studies are needed to study patient outcome when using PFAA with different severities of natural protein restrictions in patients with MMA to guide future practice.

Chronic liver involvement in urea cycle disorders.

The increased survival of urea cycle disorders (UCDs) patients has led the attention to clinical manifestations that characterize the long-term disease course. Acute and chronic liver disease have been anecdotally reported since the very first description of UCDs. However, a detailed analysis of long-term liver involvement in large patient cohorts is still needed. Chronic liver damage in UCDs has probably a multifactorial origin, but the specific underlying mechanisms of liver disease have not yet been well elucidated. In this study, we report on chronic liver involvement and on associated metabolic abnormalities in a large cohort of 102 UCD patients, followed by two reference centers in Italy. Chronic liver involvement was observed in over 60% of UCDs patients, and comparison between individual diseases showed a significant higher frequency in argininosuccinate lyase deficiency (ASLD) and in hyperornithinemia-hyperammonemia-homocitrullinemia (HHH) syndrome with elevation of transaminases and of gamma-GT in ASLD, and of alpha-fetoprotein in HHH syndrome. Also, consistent with a chronic hepatic dysfunction, ultrasound examination revealed more pronounced abnormalities in ASLD and in HHH syndrome, when compared to other UCDs. Our study highlights in a large UCDs patients' cohort that chronic liver disease is a common finding in UCDs, often with a distinct phenotype between different diseases. Furthers studies are needed to elucidate the specific involvement of different metabolic pathways in the pathogenesis of liver dysfunction in UCDs.

Prevalence and outcome of malnutrition in pediatric patients with chronic diseases: Focus on the settings of care.

BACKGROUND: Information on disease-related malnutrition and related outcomes in pediatric patients with chronic diseases in different settings of care is not available. METHODS: Consecutive eligible patients attending the out-patient clinic (n = 177) or admitted to the day-hospital clinic (n = 163) or to hospital (n = 201) were screened for the presence of malnutrition (BMI and/or height/length for age z-scores < -2). We recorded data on emergency care admissions to hospital that occurred during the 3 years before screening and related total days of stay, as well as data on emergency care admissions to hospital occurring within 6 months after screening. RESULTS: Prevalence of malnutrition was 2-fold higher (P < 0.001) in in-patients (56.7% [95% CI, 49.6-63.7]) than in patients assessed at the out-patient (33.3% [95% CI, 26.4-40.8]) and day-hospital (28.3% [95% CI, 21.5-35.8]) clinics. Estimates were heterogeneous across diagnostic groups with higher rates in patients with neurologic (61%) and cardiac (56%) diseases. Stunting was more frequent among in-patients, who also had more evident nutritional derangements. Multivariate logistic regression (covariates: age, gender, healthcare setting and disease group), showed that malnutrition (OR = 1.86 [95% CI, 1.21-2.88]; P = 0.005) was significantly associated with prolonged hospitalization (≥15 days) in the 3 years before screening. In-patients were also more likely to have been hospitalized ≥15 days (using out-patients as reference category, OR = 2.24 [95% CI, 1.39-3.63], P = 0.001), but we did not find any modifying effect (interaction) of the setting of care on the association between malnutrition and prolonged hospitalization. DISCUSSION: The rates of malnutrition in children with chronic diseases are very high and increase hospital care needs, especially when they are admitted to hospital. Nutritional care in this patient population is recommended.

Enteral nutrition in pediatric intestinal failure: does initial feeding impact on intestinal adaptation?

INTRODUCTION: Primary IF can be due to impaired gut length or impaired gut function; short bowel syndrome (SBS) is the leading cause of IF. In IF patients complete enteral starvation should be avoided whenever possible and enteral/oral nutrition (EN/ON) should be employed at the maximum tolerated amount in each phase of the clinical evolution of IF. Intraluminal nutrients have stimulatory effects on epithelial cells and on trophism that enhance intestinal adaptation. Areas covered: Evidence for nutritional interventions in pediatric IF is limited and of poor quality. Clinical practice in SBS feeding are more 'experience-based' rather than 'evidence-based' and this dearth of clinical evidence is partly due to the rarity of this condition. This review updates knowledge concerning the impact of the initial diet with EN/ON in neonatal onset SBS in the process of bowel adaption. Expert commentary: Human milk resulted the preferred starting diet and it is generally combined with amino-acids (AAs) in Northern America and with hydrolyzed proteins (HFs) in Europe; polymeric diet is rarely employed. HFs were not more effective than AAs in promoting intestinal adaptation.

Blood and hair lead levels in boys and girls living in two Sardinian towns at different risks of lead pollution.

This study reports blood and hair lead levels measured in 1998 in 222 children from two Sardinian towns: Portoscuso and Sestu. Portoscuso is in a polluted area of Sardinia due to its vicinity to the industrial zone of Portovesme. As a consequence of its economy and location, Sestu is not exposed to lead pollution. Blood lead (PbB) concentration was determined in heparinized venous blood samples by graphite furnace atomic absorption spectrophotometry (AAS). Hair lead (PbH) concentration was determined by inductively coupled plasma atomic emission spectrometry (ICP-AES). With respect to blood lead levels, the boys of Portoscuso have the highest arithmetic mean value (11.30 microg/dL), followed by the Portoscuso girls (7.39 microg/dL); they are followed, but with much lower values, by the boys (4.09 microg/dL) and girls (3.34 microg/dL) of Setsu. For hair lead levels, the Portoscuso boys have the highest arithmetic mean value (15.51 microg/g), followed by the Portoscuso girls (8.82 microg/g) and the Sestu boys (4.03 microg/g) and girls (2.83 microg/g). Therefore the mean values of PbB and PbH follow similar patterns in the boys and girls of the two Sardinian towns. Two-way ANOVA reveals a significant effect of sex and town on log PbB and log PbH. Moreover, values of the Bravais-Pearson coefficients of correlation between log PbB and log PbH are statistically significant for the total sample (r=0.5086; P<0.001), for males (r=0.4275; P<0.01), and for females (r=0.4859, P<0.001). The sensitivity of the hair lead analysis in identifying lead concentrations above 10 microg/g is 49%. The results support the hypothesis that hair lead levels can be considered an indicator of different relative exposure of populations to lead pollution.