Revised D-A-CH intake recommendations for folate: how much is needed?

The D-A-CH reference value (D-A-CH arises from the initial letters of the common country identification for the countries Germany (D), Austria (A) and Switzerland (CH)) for folate equivalents had been set at 400 µg/d for adults in the year 2000. By that time, the prevention of cardiovascular diseases through reduction of homocysteine was considered an important target of the reference value. Since that time a number of research papers revealed that in spite of an inverse association between folate-rich diet and chronic diseases, a preventive effect of folic acid intake on cardiovascular events was not supported by randomized controlled trials, and the reduction of plasma homocysteine levels to around 10-12 µmol/l did not reduce the risk for thromboembolic and cardiovascular diseases in persons already affected by these diseases. These results together with the observation that folate intakes below 400 µg/d result in a sufficient folate status justified a review of the current literature and-consequently-a reduction of the reference value to 300 µg/d for adults. This reference value is expressed as dietary folate equivalents that take into account the difference in bioavailability between folic acid and all types of folates in food. The recommendation to take a daily supplement of 400 µg of synthetic folic acid for women who intend to get pregnant and until the end of the first trimester of pregnancy is maintained.

Two patients with an identical novel mutation in the AAAS gene and similar phenotype of triple A (Allgrove) syndrome.

BACKGROUND: Triple A syndrome, also known as Allgrove syndrome, is a rare autosomal recessive disorder characterized by three cardinal symptoms: adrenal insufficiency due to ACTH insensitivity, achalasia and alacrima. Various progressive neurological abnormalities and skin changes have been described in association with the syndrome. The disease is caused by mutation in the AAAS gene on chromosome 12q13. AAAS encodes a protein named ALADIN which is part of the nuclear pore complex (NPC). The mislocalization of mutated ALADIN proteins in the cytoplasm and/or the nucleus results in an impaired protein function. Phenotypes of previously reported patients with triple A syndrome varied within and between affected families so that no genotype-phenotype could be established. METHODS: Genetic analysis was performed in two unrelated patients, their parents and one sister. AAAS coding sequences including exon-intron boundaries were amplified and sequenced using an ABI 3100 sequencing machine. PATIENTS: We present two unrelated Swiss patients with triple A syndrome demonstrating similar phenotypic characteristics. Both showed a progression of the disease presenting with adrenal insufficiency and alacrima in early childhood. At the age between 30-40 years they developed symptomatic achalasia. The pattern and severity of progressive neurological and autonomic dysfunction was comparable. In both patients molecular genetic analysis revealed an identical novel homozygous mutation (c.618delC, p.Ser207fs) in the AAAS gene. CONCLUSION: Recent genotype/phenotype studies showed a marked inter- and intrafamiliar variability in triple A syndrome. Here we present a rather tight genotype/phenotype correlation in two unrelated patients carrying the identical novel p.Ser207fs mutation in the AAAS gene.

[Headache, fever and upper abdominal colic]. / Kopfschmerzen, Fieber und Oberbauchkoliken.

A nine year old boy who had received Ceftriaxone for one week because of suspected bacterial meningoencephalitis developed colicky abdominal pain in the right upper quadrant two days after termination of Ceftriaxone treatment. Stones in the gallbladder were identified as cause of the abdominal symptoms. Ceftriaxone has been reported to result in so-called pseudo-lithiasis of the gallbladder in approximatively 45% of treated patients, 19% of which developed clinical symptoms. Generally, the gallstones dissolve spontaneously when Ceftriaxone treatment was of short duration.

Kearns-Sayre's syndrome developing in a boy who survived pearson's syndrome caused by mitochondrial DNA deletion.

A 7-year-old boy presented with bilateral ptosis and atypical retinitis pigmentosa. Before age two, he had had an Fe-refractory anemia, with neutropenia and thrombopenia. Just prior to the ophthalmic examination, the patient developed lactate acidosis, muscular hypotonia, ataxia and increased protein in the spinal fluid. Pancytopenia, pancreas dysfunction and growth retardation are the main features of Pearson's syndrome, most children not surviving beyond age three. The cause of Pearson's syndrome in our patient turned out to be a 5 kb deletion in the mitochondrial DNA. Similar deletions have been described in the Kearns-Sayre syndrome. It seems that children who survive the initial phase of Pearson's syndrome, may develop Kearns-Sayre syndrome.