Standards der ernährungsmedizinischen Versorgung in der ambulanten und stationären Pädiatrie durch spezialisierte Einrichtungen der Kinder- und Jugendmedizin

Monatsschrift Kinderheilkunde - Eine adäquate Energie- und Nährstoffversorgung ist Grundlage für ein gesundes Wachstum und Voraussetzung für die Erhaltung von Gesundheit und...     

Empfehlungen zu Ernährung und Bewegung von Kleinkindern

Monatsschrift Kinderheilkunde -     

Isovaleric acidemia: new aspects of genetic and phenotypic heterogeneity

Isovaleric acidemia (IVA) is an autosomal recessive inborn error of leucine metabolism caused by a deficiency of the mitochondrial enzyme isovaleryl-CoA dehydrogenase (IVD) resulting in the accumulation of derivatives of isovaleryl-CoA. It was the first organic acidemia recognized in humans and can cause significant morbidity and mortality. Early diagnosis and treatment with a protein restricted diet and supplementation with carnitine and glycine are effective in promoting normal development in severely affected individuals. Both intra- and interfamilial variability have been recognized. Initially, two phenotypes with either an acute neonatal or a chronic intermittent presentation were described. More recently, a third group of individuals with mild biochemical abnormalities who can be asymptomatic have been identified through newborn screening of blood spots by tandem mass spectrometry. IVD is a flavoenzyme that catalyzes the conversion of isovaleryl-CoA to 3-methylcrotonyl-CoA and transfers electrons to the electron transfer flavoprotein. Human IVD has been purified from tissue and recombinant sources and its biochemical and physical properties have been extensively studied. Molecular analysis of the IVD gene from patients with IVA has allowed characterization of different types of mutations in this gene. One missense mutation, 932C>T (A282V), is particularly common in patients identified through newborn screening with mild metabolite elevations and who have remained asymptomatic to date. This mutation leads to a partially active enzyme with altered catalytic properties; however, its effects on clinical outcome and the necessity of therapy are still unknown. A better understanding of the heterogeneity of this disease and the relevance of genotype/phenotype correlations to clinical management of patients are among the challenges remaining in the study of this disorder in the coming years.     

Programmierung von kindlichem Übergewicht durch perinatale Überflusssituation

Childhood overweight and obesity are urgent health problems with far-reaching consequences up into adulthood. Based on still poorly defined mechanisms, referred to as fetal programming, the risks of later life health problems are already determined during the earliest prenatal stages of life and appear to aggravate the overweight situation. Periconceptional maternal obesity and additional perinatal risk factors including a disproportionately high gestational weight gain, gestational diabetes and postnatal rapid weight gain in the first 2 years of life, promote the risk of developing overweight and associated metabolic disorders in childhood. Animal experimental studies provide the advantage of studying the consequences of maternal overnutrition for the offspring in a controlled setting. Adverse nutritional exposure, such as a high intake of saturated fatty acids or an additional increase of free sugar in the maternal diet exerts effects on weight status and body fat in the offspring and may result in dysfunction of metabolically active organs including adipose tissue, brain, liver and muscle. Potential underlying mechanisms may involve proinflammatory and epigenetic processes. Whether prenatal prevention concepts may have a beneficial long-term impact on later offspring health is currently unclear. Promotion of breastfeeding and avoidance of rapid postnatal weight gain in the first 2 years of life are essential components of the practicing pediatrician’s efforts for overweight prevention.     

Perinatale Programmierung des Typ-2-Diabetes

Early metabolic influences in utero increase the risk for metabolic imbalances such as type 2 diabetes mellitus in the offspring’s later life, via mechanisms referred to as fetal programming. Important perinatal risk factors for metabolic alterations in later life are intrauterine growth restriction, preconception maternal obesity, and a diabetic intrauterine milieu. As shown in human studies and experimental animal models, maternal diabetes mellitus in pregnancy can induce various long-term consequences for organ function in the offspring. Underlying mechanisms of perinatal programming involve epigenetic processes. Consecutively, gene expression may be modified, and/or structural modifications can occur in the offspring. A more detailed understanding of the early-life origins of diabetes mellitus and prediabetes is required for the development of preventive concepts and early treatment strategies.     

Propionic acidemia: neonatal versus selective metabolic screening

Background

Whereas propionic acidemia (PA) is a target disease of newborn screening (NBS) in many countries, it is not in others. Data on the benefit of NBS for PA are sparse.

Study design

Twenty PA patients diagnosed through NBS were compared to 35 patients diagnosed by selective metabolic screening (SMS) prompted by clinical findings, family history, or routine laboratory test results. Clinical and biochemical data of patients from 16 metabolic centers in Germany, Austria, and Switzerland were evaluated retrospectively. Additionally, assessment of the intelligent quotient (IQ) was performed. In a second step, the number of PA patients who have died within the past 20?years was estimated based on information provided by the participating metabolic centers.

Results

Patients diagnosed through NBS had neither a milder clinical course regarding the number of metabolic crises nor a better neurological outcome. Among NBS patients, 63% were already symptomatic at the time of diagnosis, and <10% of all patients remained asymptomatic. Among all PA patients, 76% were found to be at least mildly mentally retarded, with an IQ <69. IQ was negatively correlated with the number of metabolic decompensations, but not simply with the patients?? age. Physical development was also impaired in the majority of patients. Mortality rates tended to be lower in NBS patients compared with patients diagnosed by SMS.

Conclusion

Early diagnosis of PA through NBS seems to be associated with a lower mortality rate. However, no significant benefit could be shown for surviving patients with regard to their clinical course, including the number of metabolic crises, physical and neurocognitive development, and long-term complications.     

Low lysine diet in glutaric aciduria type I – effect on anthropometric and biochemical follow-up parameters

Background

Metabolic treatment in glutaric aciduria type I (GA-I) including a low lysine diet with lysine-free, tryptophan-reduced amino acid supplements (AAS), carnitine supplementation and early start of emergency treatment during putatively threatening episodes of intermittent febrile illness dramatically improves the outcome and thus has been recommended by an international guideline group (Kölker et al, J Inherit Metab Dis 30:5–22, 2007). However, possible affection of linear growth, weight gain and biochemical follow-up monitoring has not been studied systematically.

Methods

Thirty-three patients (n?=?29 asymptomatic, n?=?4 dystonic) with GA-I who have been identified by newborn screening in Germany from 1999 to 2009 were followed prospectively during the first six years of life. Dietary treatment protocols, anthropometrical and biochemical parameters were longitudinally evaluated.

Results

Mean daily intake as percentage of guideline recommendations was excellent for lysine (asymptomatic patients: 101 %; dystonic patients: 103 %), lysine-free, tryptophan-reduced AAS (108 %; 104 %), energy (106 %; 110 %), and carnitine (92 %; 102 %). Low lysine diet did not affect weight gain (mean SDS 0.05) but mildly impaired linear growth in asymptomatic patients (mean SDS ?0.38), while dystonic patients showed significantly reduced weight gain (mean SDS ?1.32) and a tendency towards linear growth retardation (mean SDS ?1.03). Patients treated in accordance with recent recommendations did not show relevant abnormalities of routine biochemical follow-up parameters.

Interpretation

Low lysine diet promotes sufficient intake of essential nutrients and anthropometric development in asymptomatic children up to age 6 year, whereas individualized nutritional concepts are required for dystonic patients. Revised recommendations for biochemical monitoring might be required for asymptomatic patients.     

Unbalanced cryptic 5p deletion/17p duplication identified by subtelomeric FISH in a family with a boy with chimerism and a balanced t(4;5)

The use of subtelomeric FISH probes has greatly supplemented conventional chromosome analysis in detecting cryptic anomalies in patients with mental retardation (MR), dysmorphic features, and congenital malformations. We report a 3-month-old boy who was diagnosed with ambiguous genitalia, dysmorphic features, and developmental delay. Standard chromosome studies on blood revealed a chimeric karyotype of 46,XY,t(4;5)(q31.1;q14)[46]/46,XX[4]. The boy had intra-abdominal gonads that were testicular in origin by biopsy. Multiple dysmorphic features, marked hypotonia, developmental delay, poor growth, and relative macrocephaly were noted on physical exam. His 2.5-year-old sister also presented with hypotonia, developmental delay, relative macrocephaly, and similar dysmorphic stigmata. In addition, she was diagnosed with several internal malformations. Her karyotype was 46,XX. Due to the striking phenotypic similarity, subtelomeric FISH studies were initiated in the siblings. In addition to the known balanced karyotypic abnormalities, the boy was found to have a derivative chromosome 5 with a 5pter deletion and a 17pter duplication. This cryptic abnormality was also detected in his sister. Chromosome analysis of the father revealed a subtle balanced t(5;17)(p15.31;p13.1) which was confirmed by subtelomeric FISH, whereas the mother's chromosome complement was normal. This familial constellation illustrates the usefulness of subtelomeric FISH in the diagnosis of cryptic chromosome abnormalities in patients for whom conventional karyotype does not disclose findings sufficient to explain the observed phenotypic anomalies.