Effect of Lactobacillus reuteri (DSM 17938) on methane production in patients affected by functional constipation: a retrospective study.

OBJECTIVE: Constipation is a common symptom affecting up to 30% of the Western population and is strongly associated with the presence of intestinal methanogens, which may directly inhibit motor activity. Two recent studies performed on adult and children affected by chronic constipation showed that the supplementation with L. reuteri significantly improved bowel movements. Whether its action is related to a decreasing of methane (CH4) production has never been tested. We have therefore designed a study aimed at testing this hypothesis. PATIENTS AND METHODS: Data of 20 adults (12 females, mean age 36.2 ± 13.7) affected by functional constipation, treated with the probiotic L. reuteri (DSM 17938) for 4 weeks who performed a H2/CH4 lactulose breath test (LBT) in our institution showing a CH4 production higher than 5 ppm were retrospectively analyzed from March to June 2015. Data recorded in their stool diary, reporting the frequency of defecations and stool consistency were also analysed, as well as the result of the LBT performed at the end of the treatment with L. reuteri. RESULTS: Four weeks of L. reuteri administration was associated with a significant decrease of mean CH4 production determined by LBT (from 20.8 ± 15 to 8.9 ± 8.6; p < 0.0001 CI 95%) and of AUC value (from 5101.5 ± 3571.13 to 2128.4 ± 2110.8; p < 0.0001 CI 95%). Moreover, a total disappearance of CH4 production (< 5 ppm at LBT) was observed in 11 patients, while, we did not observe any significant decrease of H2 production (from 13.2 ± 8.8 to 11.4 ± 7.3, CI 95%, n.s.). CONCLUSIONS: This study highlights for the first time the beneficial effect of Lactobacillus reuteri (DSM 17938) on chronic constipation, via a significant decrease of CH4 production.

Mitochondrial DNA haplogroups may influence Fabry disease phenotype.

While the genetic origin of Fabry disease (FD) is well known, it is still unclear why the disease presents a wide heterogeneity of clinical presentation and progression, even within the same family. Emerging observations reveal that mitochondrial impairment and oxidative stress may be implicated in the pathogenesis of FD. To investigate if specific genetic polymorphisms within the mitochondrial genome (mtDNA) could act as susceptibility factors and contribute to the clinical expression of FD, we have genotyped European mtDNA haplogroups in 77 Italian FD patients and 151 healthy controls. Haplogroups H and I, and haplogroup cluster HV were significantly more frequent in patients than controls. However, no correlation with gender, age of onset, organ involvement was observed. Our study seems to provide some evidence of a contribution of mitochondrial variation in FD pathogenesis, at least in Italy.

Propranolol and prednisolone combination for the treatment of segmental haemangioma in PHACES syndrome.

Posterior fossa malformations-haemangiomas-arterial anomalies-cardiac defects-eye abnormalities-sternal cleft and supraumbilical raphe syndrome (also known as PHACES syndrome) is a rare neurocutaneous disorder. Children presenting with these manifestations need careful ophthalmological, cardiac and neurological assessment. They may have one or more of these extracutaneous manifestations, the most common being cerebral and cardiovascular anomalies. There is controversy about treating these children with propranolol especially if they have cerebrovascular involvement with narrow, dysplastic or absent blood vessels. The concern with propranolol is that hypotension may lead to reduced cerebral blood flow and neurological consequences. Prior to propranolol the systemic treatment for haemangiomas was prednisolone and then the concern was the opposite, namely hypertension. Our proposal was whether a combination of these two drugs would provide a safer and faster recovery. We report three retrospective cases of PHACES syndrome, each of whom received treatment with a combination of propranolol and prednisolone: two children were started on prednisolone and propranolol was added because the haemangiomas failed to respond adequately; the third child was started on propranolol and developed peripheral ischaemia and ulceration necessitating a reduction in dose addition of a low dose of prednisolone. All three patients, who failed on the one treatment, responded well to combination therapy without any significant complications. These outcomes suggest that for some patients with PHACES syndrome the use of combination treatment with propranolol and prednisolone could be advantageous, potentially allowing for the introduction of low doses of each with an enhanced combined effect. The doses can be increased gradually depending on the magnetic resonance imaging findings.

Mutation identification of Fabry disease in families with other lysosomal storage disorders.

Fabry disease (FD) is an X-linked lysosomal storage disorder (LSD) caused by the deficiency of the enzyme α-galactosidase. It exhibits a wide clinical spectrum that may lead to a delayed or even missed diagnosis and the real incidence can be underestimated. We report the cases of two unrelated Italian families in whom FD was incidentally diagnosed in two females. In both families, the risk for other lysosomal disorders was known from other members affected by fucosidosis or mucopolysaccharidosis I Hurler/Scheie. Some subjects were simultaneously heterozygous for Fabry and the other lysosomal deficiency. Our study shows that the risk for more than one LSDs can occur in a family pedigree. The diagnosis of Fabry in female probands represents a diagnostic challenge, as symptoms and signs can be variably present because of the random X-chromosome inactivation.

Angiokeratoma: decision-making aid for the diagnosis of Fabry disease.

Isolated angiokeratomas are common benign cutaneous lesions, generally deemed unworthy of further investigation. In contrast, diffuse angiokeratomas should alert the physician to a possible diagnosis of Fabry disease, a rare X-linked lysosomal storage disorder, characterized by α-galactosidase deficiency. Glycosphingolipids accumulate in cells throughout the body resulting in progressive multi-organ failure. Difficulties are encountered when trying to interpret the significance of angiokeratomas because they may also occur in other lysosomal storage disorders and rarely in an isolated manner in Fabry disease. We present an algorithm for the classification of angiokeratomas which might prove useful for the diagnosis and management of Fabry disease. Assessment of the clinical features and location of the lesions, personal and family history, skin biopsy, dermoscopy and electron microscopy imaging are sequential steps in the diagnostic process. Assessing the deficiency of α-galactosidase enzyme activity is essential to confirm the diagnosis in males, while mutation analysis is always needed in females. Potentially this algorithm can change the current approach to patients when Fabry disease is suspected, thus improving the diagnostic strategy and management of this disorder. It remains to be decided whether the use of an algorithm might reduce the number of genetic consultations. As evidence has shown the efficacy of enzyme replacement therapy in halting progression of the disease before the onset of irreversible organ damage, it is advisable to aim at an early diagnosis in order to achieve timely initiation of effective treatment with benefits for patients and appropriate use of medical resources.