Effects of histamine and diamine oxidase activities on pregnancy: a critical review.

BACKGROUND: Histamine has been assumed to contribute to embryo-uterine interactions due to its vasoactive, differentiation and growth-promoting properties. However, its exact functions in pregnancy are unclear. The histamine-degrading enzyme diamine oxidase (DAO) is produced in high amounts by the placenta and has been supposed to act as a metabolic barrier to prevent excessive entry of bioactive histamine from the placenta into the maternal or fetal circulation. METHODS: The literature available on PubMed published in English between 1910 and 2008 has been searched using the isolated and combined key words histamine, diamine oxidase, pregnancy, placenta, endometrium, miscarriage, implantation, pre-eclampsia, intrauterine growth retardation, diabetes and embryonic histamine-releasing factor (EHRF). RESULTS: High expression of the histamine-producing enzyme histidine decarboxylase in the placenta, histamine receptors at the feto-maternal interface and the existence of an EHRF suggest a physiological role of histamine during gestation. The balance between histamine and DAO seems to be crucial for an uncomplicated course of pregnancy. Reduced DAO activities have been found in multiple heterogeneous complications of pregnancy such as diabetes, threatened and missed abortion and trophoblastic disorders. Whether women with histamine intolerance suffer from more complicated pregnancies and higher abortion rates due to impaired DAO activities and if low DAO levels or genetic modifications in the DAO gene might therefore represent a prognostic factor for a higher risk of abortion, has not been investigated yet. CONCLUSIONS: Low activities of the histamine-degrading enzyme DAO might indicate high-risk pregnancies, although high intra- and interindividual variations limit its value as a screening tool.

LHON/MELAS overlap syndrome associated with a mitochondrial MTND1 gene mutation.

Pathogenic point mutations in the mitochondrial MTND1 gene have previously been described in association with two distinct clinical phenotypes -- Leber hereditary optic neuropathy (LHON) and mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Here we report the first heteroplasmic mitochondrial DNA (mtDNA) point mutation (3376G>A) in the MTND1 gene associated with an overlap syndrome comprising the clinical features of both LHON and MELAS. Muscle histochemistry revealed subtle mitochondrial abnormalities, while biochemical analysis showed an isolated complex I deficiency. Our findings serve to highlight the growing importance of mutations in mitochondrial complex I structural genes in MELAS and its associated overlap syndromes.

Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans, caused by homozygous absence of the survival motor neuron gene 1 (SMN1). SMN2, a copy gene, influences the severity of SMA and may be used in somatic gene therapy of patients with SMA in the future. We present a new, fast, and highly reliable quantitative test, based on real-time LightCycler PCR that amplifies either SMN1 or SMN2. The SMN1 copies were determined and validated in 329 carriers and controls. The specificity of the test is 100%, whereas the sensitivity is 96.2%. The quantitative analysis of SMN2 copies in 375 patients with type I, type II, or type III SMA showed a significant correlation between SMN2 copy number and type of SMA as well as duration of survival. Thus, 80% of patients with type I SMA carry one or two SMN2 copies, and 82% of patients with type II SMA carry three SMN2 copies, whereas 96% of patients with type III SMA carry three or four SMN2 copies. Among 113 patients with type I SMA, 9 with one SMN2 copy lived <11 mo, 88/94 with two SMN2 copies lived <21 mo, and 8/10 with three SMN2 copies lived 33-66 mo. On the basis of SMN2 copy number, we calculated the posterior probability that a child with homozygous absence of SMN1 will develop type I, type II, or type III SMA.