Ketogenic diet as a glycine lowering therapy in nonketotic hyperglycinemia and impact on brain glycine levels

BACKGROUND: Nonketotic hyperglycinemia (NKH) is a severe neurometabolic disorder characterized by increased glycine levels. Current glycine reduction therapy uses high doses of sodium benzoate. The ketogenic diet (KD) may represent an alternative method of glycine reduction. AIM: We aimed to assess clinical and biochemical effects of two glycine reduction strategies: high dose benzoate versus KD with low dose benzoate. METHODS: Six infants with NKH were first treated with high dose benzoate therapy to achieve target plasma glycine levels, and then switched to KD with low dose benzoate. They were evaluated as clinically indicated by physical examination, electroencephalogram, plasma and cerebral spinal fluid amino acid levels. Brain glycine levels were monitored by magnetic resonance spectroscopy (MRS). RESULTS: Average plasma glycine levels were significantly lower with KD compared to benzoate monotherapy by on average 28%. Two infants underwent comparative assessments of brain glycine levels via serial MRS. A 30% reduction of brain glycine levels was observed in the basal ganglia and a 50% reduction in the white matter, which remained elevated above normal, and was equivalent between the KD and high dose benzoate therapies. CSF analysis obtained while participants remained on the KD showed a decrease in glycine, serine and threonine levels, reflecting their gluconeogenetic usage. Clinically, half the patients had seizure reduction on KD, otherwise the clinical impact was variable. CONCLUSION: KD is an effective glycine reduction method in NKH, and may provide a more consistent reduction in plasma glycine levels than high-dose benzoate therapy. Both high-dose benzoate therapy and KD equally reduced but did not normalize brain glycine levels even in the setting of low-normal plasma glycine

Health symptoms in residents living near shale gas activity: A retrospective record review from the Environmental Health Project

Increasing evidence demonstrates an association between health symptoms and exposure to unconventional natural gas development (UNGD). The purpose of this study is to describe the health of adults in communities with intense UNGD who presented for evaluation of symptoms. Records of 135 structured health assessments conducted between February 2012 and October 2015 were reviewed retrospectively. Publicly available data were used to determine proximity to gas wells. Analysis was restricted to records of adults who lived within 1km of a well in Pennsylvania and denied employment in the gas industry (n=51). Symptoms in each record were reviewed by a physician. Symptoms that could be explained by pre-existing or concurrent conditions or social history and those that began or worsened prior to exposure were excluded. Exposure was calculated using date of well drilling within 1km. The number of symptoms/participant ranged from 0 to 19 (mean=6.2; SD=5.1). Symptoms most commonly reported were: sleep disruption, headache, throat irritation, stress or anxiety, cough, shortness of breath, sinus problems, fatigue, nausea, and wheezing. These results are consistent with findings of prior studies using self-report without physician review. In comparison, our results are strengthened by the collection of health data by a health care provider, critical review of symptoms for possible alternative causes, and confirmation of timing of exposure to unconventional natural gas well relative to symptom onset or exacerbation. Our findings confirm earlier studies and add to the growing body of evidence of the association between symptoms and exposure to UNGD. Keywords: Hydraulic fracturing, Health, Fracking, Shale gas, Unconventional ga