A survey of natural protein intake in Dutch phenylketonuria patients: insight into estimation or measurement of dietary intake.

This study investigated which methods patients and parents used to determine phenylalanine (Phe) intake and the relationship between the methods applied, age, and blood Phe concentration, as this practice had not been studied before in relation to metabolic control. A questionnaire was sent to 327 Dutch phenylketonuria patients (age 0-29 years) to investigate the method used to determine Phe intake (either by estimation, exact measurement, or a combination of both). Mean blood Phe concentration of each individual patient was related to the method reported to be used. Three different age groups (<10 years, > or =10-15 years, and > or =16 years) were distinguished. The response rate for the questionnaires was 73%. In these 188 patients, data for both Phe concentrations and questionnaires could be used. Of these, 75 used exact measurement, 75 used estimation, and 38 used both methods. The number of patients that estimated Phe intake clearly increased with age. Whatever method was used, an increase in Phe concentrations was seen with age. During childhood, exact measurement was used more frequently, and from adolescence on estimation was used more frequently. The method (exact measurement and/or estimation) did not result in statistically different Phe concentrations in any of the three age groups, although blood Phe concentration tended to be lower in adolescence using exact measurement. Data suggest that estimation and exact measurement of Phe intake are both reliable methods. Therefore, in addition to exact measurement, patients should be instructed in both methods at an early age, so that both methods can be used adequately.

Systematic review of the occurrence of infantile colic in the community.

AIMS: To assess the occurrence of infantile colic in the community and the need for professional help; and to study the influences of potential determinants of infantile colic. METHODS: Surveys were identified by a systematic search in Medline (1966-98) and Embase (1988-98). Retrieved publications were checked for references. Studies selected were community based, prospective, and retrospective surveys on the occurrence of infantile colic published in English, German, French, or Dutch. Occurrence rates were calculated as percentages. Methodological quality of the surveys was assessed by two assessors independently with a standardised criteria list containing items on method of data gathering, definition of colic, and drop out rate. RESULTS: Fifteen community based surveys were identified. The methodological quality varied considerably and was generally low. Even the two most methodologically sound prospective studies yielded widely varying cumulative incidence rates of 5-19%. Referral rates or the need to seek help because of crying were consistently lower than occurrence rates for prolonged crying as such. Gender, socioeconomic class, type of feeding, family history of atopy, and parental smoking were not shown to be associated with colic. CONCLUSION: Occurrence rates of infantile colic vary greatly according to methodological quality. A considerable number of parents reporting prolonged crying do not seek or need professional help.

Transaldolase deficiency: liver cirrhosis associated with a new inborn error in the pentose phosphate pathway.

This article describes the first patient with a deficiency of transaldolase (TALDO1 [E.C.2.2.1.2]). Clinically, the patient presented with liver cirrhosis and hepatosplenomegaly during early infancy. In urine and plasma, elevated concentrations of ribitol, D-arabitol, and erythritol were found. By incubating the patient's lymphoblasts and erythrocytes with ribose-5-phosphate and subsequently analyzing phosphate sugar metabolites, we discovered a deficiency of transaldolase. Sequence analysis of the transaldolase gene from this patient showed a homozygous deletion of 3 bp. This deletion results in absence of serine at position 171 of the transaldolase protein. This amino acid is invariable between species and is located in a conserved region, indicating its importance for enzyme activity. The detection of this new inborn error of pentose metabolism has implications for the diagnostic workup of liver problems of unknown etiology.

Infantile colic: crying time reduction with a whey hydrolysate: A double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To determine the effectiveness of whey hydrolysate formula in the treatment of infantile colic in a primary care setting in the Netherlands. STUDY DESIGN: Randomized, double-blind, parallel trial with a 1-week qualification period and a 1-week intervention period. Participants. Forty-three healthy, thriving, formula-fed infants, <6 months old, crying >3 hours per day on at least 3 days per week. Infants were randomized to whey hydrolysate formula (n = 23) or standard formula (n = 20). MAIN OUTCOME MEASURE: Difference in duration of crying (minutes per day) between qualification week and intervention week. RESULTS: Analysis according to the intention to treat principle showed a difference in the decrease of crying duration of 63 minutes per day [95% confidence interval: 1-127 minutes per day] in favor of the whey hydrolysate formula. Five infants did not complete the trial. The scope of the study was not sufficient to expect significant differences in the subgroup analyses. CONCLUSIONS: An extensively hydrolyzed whey formula is effective in reducing the duration of crying in a primary care setting.

Diagnostic dilemmas and results of treatment for chronic constipation.

Chronic functional constipation (CFC) may be difficult to recognise and information regarding its long term prognosis is scarce. The records of 244 children with CFC, aged 0-18 years, were analysed for symptoms at presentation and results of treatment, and long term outcome was evaluated by means of a telephone interview in 137 patients discharged for more than one year. The patients presented with a great variety of symptoms, only 22% having infrequent defecation of increased consistency, another 22% having an obviously normal defecation pattern. The mean duration of treatment was 13 months. At the time of discharge, 69% of the patients still used laxatives. At a median of four years after discharge, 66% of the children were free of symptoms and without medication, 39% having experienced a recurrence. It is concluded that CFC may be difficult to recognise and can be alleviated by an intensive laxative regimen. Recurrence of symptoms is common, but the long term prognosis is good in most patients.

Hydrogen breath test as a simple noninvasive method for evaluation of carbohydrate malabsorption during exercise.

The aim of this study was to examine hydrogen (H2) production with the hydrogen breath test (HBT) after ingesting primarily digestible carbohydrate (CHO) during 3 h of 75% maximal oxygen consumption exercise. This was done to indicate CHO overflow in the colon which may occur when gastric emptying, intestinal transit and CHO absorption are not matched and CHO accumulates in the colon where it is subject to bacterial degradation. Further, this study was designed to assess breath H2 production as a function of the type of CHO ingested and the type of exercise. A group of 32 male triathletes performed three exercise trials at 1-week intervals with either a semisolid (S) intake, an equal energy fluid intake (F) or a fluid placebo (P). Each trial consisted of cycling (sessions 1 and 3) and running (sessions 2 and 4). The mixed-expired H2 concentrations in the resting and "recovery" periods (5 min after each session) did not change significantly in time and did not differ among intakes. There were also no significant differences in H2 concentrations between resting and "recovery" conditions. During exercise, H2 concentrations decreased three to six-fold in comparison to resting and recovery levels and differed among intakes (ANOVA; P < 0.05). The H2 concentrations were almost continuously lower with P than with F and S. The H2 concentrations were significantly higher during running than during cycling. During exercise, we found that CHO overflow could be compared among intakes and between exercise types by using the HBT, provided the influence of other factors on H2 excretion--ventilation and intestinal blood flow--was similar for each condition.

[Idiopathic neonatal hepatitis]. / Idiopathische neonatale hepatitis.

Idiopathic neonatal hepatitis is one of the more important causes of neonatal cholestasis. It is regarded one of the clinical presentations of 'idiopathic obstructive cholangiopathy', just like extrahepatic biliary atresia. Is it not possible to discriminate between intrahepatic and extrahepatic causes of neonatal cholestasis, or between idiopathic neonatal hepatitis and metabolic, infectious, or toxic causes, by using clinical or laboratory parameters. Liver histology is slightly more helpful: giant cell formation, focal liver necrosis, and lymphocytic and neutrophilic infiltration may be found in idiopathic neonatal hepatitis. In infectious hepatitis liver pathology mostly is only a lesser part of the symptomatology. Sporadic idiopathic neonatal hepatitis has a better prognosis than familial; about 75% of children with sporadic hepatitis experience complete recovery as compared to less than 25% of children with familial hepatitis. Therapy is confined to the prevention and treatment of complications such as itching, portal hypertension and variceal bleeding, and (fat) malabsorption.

Plasma polyol levels in patients with cataract.

Galactitol and sorbitol concentrations in plasma were determined in patients (with or without cataract) in whom homo- or heterozygosity for galactokinase, galactose-1-phosphate uridyltransferase, systemic or peripheral UDP-galactose epimerase and sorbitol dehydrogenase deficiency was confirmed. For the above disorders it can be concluded that elevation of plasma polyols is not always related to the presence or absence of cataract. In all cases with cataract, however, the plasma galactitol or sorbitol levels were elevated. In another group of patients with unexplained congenital or infantile cataracts, but without apparent enzyme defects, mild to moderately elevated concentrations of plasma galactitol or sorbitol were found in about 45%. In 8% of this group the cataract and the elevated plasma galactitol concentration could possibly have been related to partial maternal enzyme deficiency. In all the other cases the elevated plasma polyol concentration remains unexplained but could indicate a further cause of cataract formation due to a hitherto unknown galactose or glucose metabolic aberration.

Apple juice, fructose, and chronic nonspecific diarrhoea.

Apple juice contains fructose and sorbitol, substances that have been shown to be incompletely absorbed by most people. As this might have clinical consequences, especially in young children, we investigated the absorption of the carbohydrate content of apple juice in apple juice consuming toddlers with chronic nonspecific diarrhoea as compared to controls, using the breath hydrogen (H2) test. Incomplete absorption of the carbohydrates from 250 ml of apple juice, as indicated by a maximum breath H2 increase of greater than or equal to 20 parts per million (ppm), was found in all nine patients (mean +/- SEM 57 +/- 8 ppm), and in five out of eight controls (22 +/- 7 ppm) (P less than 0.01). Six patients were retested with apple juice "enriched" with glucose, which is known to improve fructose absorption. The maximum breath H2 increase as well as the area under the breath H2 curve decreased significantly. It was thus estimated that fructose accounted for 80% of the incomplete absorption and sorbitol for 20%. Elimination of apple juice from the diets of the nine patients resulted in normalisation of both the frequency and the consistency of the stools. Incomplete absorption of the carbohydrates, particularly fructose, from apple juice seems to be quite common, and may contribute to chronic diarrhoea in young children.

A milder variant of Zellweger syndrome.

A 4.5-year-old male patient is described with chorioretinopathy, minor facial anomalies, delayed closure of the fontanel, mental retardation, moderate hypotonia, epilepsy and hepatic fibrosis. Postural control, intentional vocalising and manual dexterity were superior to the performance of patients with classical Zellweger syndrome (ZS). Morphologically distinct peroxisomes were absent in the liver. In blood elevated pipecolic acid levels and abnormal levels of bile acid intermediates were found. The plasmalogen content of erythrocytes was normal. In fibroblasts we found an accumulation of very long chain fatty acids, decreased activity of acyl CoA:dihydroxyacetone phosphate acyltransferase, and impaired de novo biosynthesis of plasmalogens. On the basis of these clinical, ultrastructural and biochemical characteristics we assume that this patient represents a milder variant of the classical cerebro-hepato-renal syndrome of Zellweger.