Recommendations for diagnosing and managing individuals with glutaric aciduria type 1: Third revision.

Glutaric aciduria type 1 is a rare inherited neurometabolic disorder of lysine metabolism caused by pathogenic gene variations in GCDH (cytogenic location: 19p13.13), resulting in deficiency of mitochondrial glutaryl-CoA dehydrogenase (GCDH) and, consequently, accumulation of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid and glutarylcarnitine detectable by gas chromatography/mass spectrometry (organic acids) and tandem mass spectrometry (acylcarnitines). Depending on residual GCDH activity, biochemical high and low excreting phenotypes have been defined. Most untreated individuals present with acute onset of striatal damage before age 3 (to 6) years, precipitated by infectious diseases, fever or surgery, resulting in irreversible, mostly dystonic movement disorder with limited life expectancy. In some patients, striatal damage develops insidiously. In recent years, the clinical phenotype has been extended by the finding of extrastriatal abnormalities and cognitive dysfunction, preferably in the high excreter group, as well as chronic kidney failure. Newborn screening is the prerequisite for pre-symptomatic start of metabolic treatment with low lysine diet, carnitine supplementation and intensified emergency treatment during catabolic episodes, which, in combination, have substantially improved neurologic outcome. In contrast, start of treatment after onset of symptoms cannot reverse existing motor dysfunction caused by striatal damage. Dietary treatment can be relaxed after the vulnerable period for striatal damage, that is, age 6 years. However, impact of dietary relaxation on long-term outcomes is still unclear. This third revision of evidence-based recommendations aims to re-evaluate previous recommendations (Boy et al., J Inherit Metab Dis, 2017;40(1):75-101; Kolker et al., J Inherit Metab Dis 2011;34(3):677-694; Kolker et al., J Inherit Metab Dis, 2007;30(1):5-22) and to implement new research findings on the evolving phenotypic diversity as well as the impact of non-interventional variables and treatment quality on clinical outcomes.

Are heterocygotes for classical homocystinuria at risk of vitamin B12 and folic acid deficiency?

OBJECTIVES/DESIGN: Comparative cross-sectional study to assess homocysteine and vitamin status in carriers of CBS gene mutations. METHOD: Subjects included 34 parents (13 males, 21 females, age 27-59 years) of 30 patients with classical homocystinuria due to homozygous cystathionine beta-synthase deficiency. Control subjects were matched for gender and age (13 males, 21 females, age 25-59 years). All subjects were of Qatari origin, had normal liver and renal function tests and had not taken drugs or vitamin supplements prior to the study. The concentrations of homocysteine, folic acid and vitamins B6 and B12 in blood were determined after an overnight fast. RESULTS: Heterozygous carriers had significantly increased fasting levels of homocysteine compared to controls (9.1 vs. 8.1 micromol/l, P=0.012). Both folic acid (328 vs. 478 pmol/l, P=0.002) and vitamin B12 concentrations (232 vs. 287 pmol/l, P=0.013) were reduced whilst there was no significant difference in vitamin B6 levels between the two groups (5.8 vs. 6.44 microg/l). CONCLUSIONS: Increased homocysteine concentrations in CBS gene mutation carriers are associated with reduced concentrations of folic acid and vitamin B12 in blood. In view of the adverse effects of mild hyperhomocysteinemia, routine testing of vitamin status in parents of homocystinuria patients may be warranted. The causal relationship and pathophysiological consequences are uncertain; it is likely that CBS gene mutation carriers need higher doses of dietary vitamins.

Herbal medicine with curcuma and fumitory in the treatment of irritable bowel syndrome: a randomized, placebo-controlled, double-blind clinical trial.

OBJECTIVE: Irritable bowel syndrome (IBS) is a common functional disorder for which there is no reliable medical treatment. The aim of this study was to determine the efficacy of two herbal remedies used in the treatment of IBS. MATERIAL AND METHODS: In a randomized, double-blind, placebo-controlled trial, IBS patients were randomly assigned to one of three treatment groups: 1) Curcuma xanthorriza 60 mg daily (curcuma group) (n=24), 2) Fumaria officinalis 1500 mg daily (fumitory group) (n=24) and 3) placebo (n=58). The study treatment was applied three times a day for 18 weeks. The main outcome parameters were changes in global patient ratings of IBS-related pain and distension on a visual analogue scale (0-50 mm) between baseline and at the end of treatment. Additional outcome parameters included global assessments of changes in IBS symptoms and psychosocial stress caused by IBS. RESULTS: A total of 106 patients (mean age 48+/-12 years, 63% F) were included in the intention-to-treat group. IBS-related pain decreased by -0.9+/-11.5 (mm+/-SD) in the fumitory group, -0.3+/-9.9 in the placebo group and increased by 2.0+/-9.5 in the curcuma group (p=0.81). IBS-related distension decreased by -1.4+/-12.5 in the curcuma group, -2.1+/-9.2 in the placebo group and increased by 0.3+/-9.3 in the fumitory group (p=0.48). Additionally, the global assessment of changes in IBS symptoms and psychological stress due to IBS did not differ significantly among the three treatment groups. CONCLUSIONS: Neither fumitory nor curcuma showed any therapeutic benefit over placebo in patients with IBS. Therefore, the use of these herbs for the treatment of IBS cannot be recommended.

Integration of complementary and alternative medicine into German medical school curricula -- contradictions between the opinions of decision makers and the status quo.

INTRODUCTION: There is a growing demand for complementary and alternative medicine (CAM) in Western societies. This trend has lead to the gradual integration of CAM courses into medical school curricula. The aim of this study was to survey key decision makers at German medical schools with regard to their views on CAM and to examine the extent to which CAM has already been integrated in the German medical school system. MATERIALS AND METHODS: A questionnaire was sent to 753 clinic and institute directors at German medical schools. RESULTS: A total of 500 questionnaires (66%) were returned. 39% of respondents had a positive opinion of CAM, 27% had a neutral opinion and 31% had a negative opinion. 3% of respondents were unsure. The CAM therapies viewed most positively were osteopathy (52%), acupuncture (48%), and naturopathy (41%). Most respondents were in favor of integrating CAM into the medical system. However, a larger percentage favored its use in research (61%) and teaching (59%) rather than in the treatment of patients (58%). Only 191 respondents (38%) indicated that CAM treatment methods had been integrated into the curriculum of their respective medical schools. In these schools, CAM was mainly used in patient treatment (35%), followed by research (22%) and education (21%). CONCLUSIONS: Our data show that the majority of respondents were in favor of integrating CAM into medical school curricula. However, at the time of our survey, only a small percentage of medical schools had actually put this into practice. The reasons for this discrepancy are unclear and should be further investigated.