Developmental changes of oxalate excretion in enterally fed preterm infants.

To further substantiate gestational age-related changes in oxalate excretion, we studied urinary oxalate excretion in 66 preterm infants born at 23.4-34.7 weeks of gestation. Spot urine of 66 preterm infants was analysed by ion chromatography as soon as they were completely orally fed with enriched breast milk and/or special preterm milk formula (days 7 to 57 of postnatal life). Infants with evidence of renal, gastrointestinal, muscular or metabolic disease were not included. Newborns on parenteral nutrition were excluded. Oxalate/creatinine ratios (Ox/Cr) decreased with gestational age (three age groups: group 1, 23 0/7-28 0/7; group 2, 28 1/7-32 0/7; and group 3, 32 1/7-35 0/7 weeks of gestation). The mean Ox/Cr was highest in group 1 (398.2 mmol/mol +/- 116.8; n = 21). Differences between groups 1 + 3 were statistically significant; p = 0.001; those between groups 1 + 2 and between groups 2 + 3 were not. Ox/Cr correlated inversely with gestational and maturational age (r = -0.41, p = 0.001; r = -0.33, p = 0.007) and positively with postnatal age (r = 0.32, p = 0.008). It correlated inversely with birth weight as well as actual weight at sample collection (r = -0.46 and -0.44, p < 0.001). Ox/Cr was significantly linked to energy and carbohydrate intake (r = 0.3 and 0.4, p = 0.03 and 0.001). These results were independent of sex. In the present study we show that urinary oxalate excretion in preterm infants depends on gestational age.

Diagnostic work-up and management of patients with isolated methylmalonic acidurias in European metabolic centres.

The long-term outcome of patients with methylmalonic aciduria (MMA) is still uncertain due to a high frequency of complications such as chronic renal failure and metabolic stroke. The understanding of this disease is hampered by a huge variation in the management of these patients. The major aim of this study was to evaluate the current practice in different European metabolic centres. A standardized questionnaire was sent to 20 metabolic centres asking for standard procedures for confirmation of diagnosis, testing cobalamin responsiveness, dietary treatment, pharmacotherapy, and biochemical and clinical monitoring. Sixteen of 20 metabolic centres (80%) returned questionnaires on 183 patients: 89 of the patients were classified as mut(0), 36 as mut(-), 13 as cblA, 7 as cblB, and 38 as cblA/B. (1) Confirmation of diagnosis: All centres investigate enzyme activity by propionate fixation in fibroblasts; six centres also perform mutation analysis. (2) Cobalamin response: Ten centres follow standardized protocols showing large variations. A reliable exclusion of nonspecific effects has not yet been achieved by these protocols. (3) Long-term treatment: In cobalamin-responsive patients, most centres use hydroxocobalamin (1-14 mg/week i.m. or 5-20 mg/week orally), while two centres use cyanocobalamin. All cobalamin-nonresponsive patients and most cobalamin-responsive patients are supplemented with L: -carnitine (50-100 mg/kg per day). Fourteen centres use intestinal decontamination by antibiotic therapy. Most centres follow D-A-CH (n = 6) or Dewey (n = 4) recommendations for protein requirements. Fourteen centres regularly use precursor-free amino acid supplements. Standardized monitoring protocols are available in seven centres, again showing high variability.

Novel mutations in exon 6 of the GFAP gene affect a highly conserved if motif in the rod domain 2B and are associated with early onset infantile Alexander disease.

Alexander disease is a rare disorder of cerebral white matter due to a dysfunction of astrocytes. The most common infantile form presents as a megalencephalic leukodystrophy. Mutations of the GFAP gene, encoding Glial Fibrillary Acidic Protein, have been recognized as the cause of Alexander disease. Glial Fibrillary Acidic Protein is the major intermediate filament protein in astrocytes, its functional rod domain is conserved in sequence and structure among other intermediate filament proteins. We report here two cases of infantile Alexander disease with early onset and severe course, caused by DE NOVO mutations A364 V and Y366C. Both affected GFAP residues are part of a highly conserved coiled-coil trigger motif in the C-terminal end of segment 2B, probably required for the stability of intermediate filament molecules. Comparable effects are seen with mutations of the corresponding residues of the gene coding for keratin 14, another intermediate filament, this further supports the hypothesis that these positions of the trigger motif are generally critical for a normal function of intermediate filaments.

[Maternal vitamin B12 deficiency: cause for neurological symptoms in infancy]. / Mütterlicher Vitamin-B12-Mangel: Ursache neurologischer Symptomatik im Säuglingsalter.

BACKGROUND: Symptoms of Vitamin B (12) deficiency in infancy include growth retardation, regression of psychomotor development, muscular hypotonia and brain atrophy. Besides an inappropriate vegetarian diet of the infants, a vegan diet or a pernicious anaemia of the mother may lead to an insufficient vitamin B (12) supply of the child. PATIENTS AND METHODS: We report here the neurological symptoms of 4 fully breast-fed infants from mothers on vegan diet or with pernicious anaemia. DISCUSSION AND CONCLUSION: Vitamin B (12) deficiency can easily be diagnosed by detection of methylmalonic acid when measuring the organic acids in urine. Vitamin B (12) deficiency should be avoided or diagnosed as early as possible since a supplementation of mother and child can prevent neurological symptoms of the baby. Furthermore, the neurological symptoms of the infant with manifest vitamin B (12) deficiency are (partially) reversible.

Absence of cytochrome c oxidase activity in a boy with dysfunction of renal tubules, brain and muscle.

We report on a boy who developed proximal renal tubular acidosis with loss of carnitine at the age of about 6 months. A few months later he began to suffer from progressive muscular weakness and neurological disturbances. Blood biochemistry showed elevated lactate and beta-hydroxybutyrate with increased lactate/pyruvate and beta-hydroxybutyrate/acetoacetate ratios. A high urinary excretion of lactate and citric acid cycle intermediates was found. These results indicated a defect of the mitochondrial respiratory chain. Analysis of biopsy material from skeletal muscle revealed low activities of all respiratory chain complexes. In muscle and fibroblasts cytochrome c-oxidase (complex IV) was absent. Despite high dose multi-vitamin therapy the boy died at the age of 30 months from central respiratory failure. At autopsy the neuropathological diagnosis of Leigh disease was made.