High-dose benzoate treatment aimed at reducing plasma glycine levels to normal reduces seizures and increases wakefulness in patients with nonketotic hyperglycinaemia (NKH). Since benzoate metabolism is dependent on the available glycine pool, and since the glycine pool is variably affected by the deficiency in the glycine cleavage enzyme system, we examined the importance of interpatient variability in benzoate requirement. To correct for the dietary glycine contribution, the glycine index was introduced as the molar requirement of benzoate dose necessary to normalize plasma glycine levels and subtracting from that the dietary glycine intake, both corrected for weight. The glycine index varied between 3.62 and 4.87 mmol/kg per day in five patients with a poor neurodevelopmental outcome and between 0.92 and 1.90 mmol/kg per day in four patients with a better neurodevelopmental outcome, and was 2.54 mmol/kg per day in a single patient with an intermediate outcome. The glycine index was stable over time within each patient. Exceeding the balance by either increasing food glycine intake or decreasing the benzoate dose resulted in increased glycine levels. Exceeding the glycine tolerance by increasing benzoate resulted in elevated and toxic levels of benzoate. The glycine index is a stable, individually specific parameter in patients with NKH. It has clinical consequences for the dose of benzoate required and the role of dietary management. Through its correlation with neurodevelopmental outcome, the glycine index points to potential genetic factors that could contribute to the psychomotor retardation in NKH.

ObjectivesTo identify family planning and pregnancy (FPP) issues for female patients of childbearing age living with a chronic inflammatory disease and to assess whether current clinical practice routinely provides adequate support to alleviate these concerns.SettingMultinational survey and an analysis of online patient activity.ParticipantsPremenopausal women (aged 20–45 years; N=969) were surveyed in the USA, the UK, Germany, France, Italy and Spain. Rheumatologists were surveyed in Germany (N=50), France (N=50), Italy (N=50) and the USA (N=100), and gastroenterologists were also surveyed in the USA (N=100).Primary and secondary outcome measuresTwo online surveys were undertaken to identify FPP issues for physicians and patients. The surveys examined the frequency of dialogue on these topics between physicians and patients, alongside assessment of patient satisfaction regarding these conversations. Online analysis identified key themes for patient discussion outside their doctors’ office/clinic/surgery.Results32–56% of physicians spontaneously reported having talked about FPP with their female patients of childbearing age. When prompted, the majority of rheumatologists (74–92%) and gastroenterologists (74%) reported having discussed conception/pregnancy with female patients; however, less than half reported consulting their patient's treating general practitioner/gynaecologist about these topics. The majority of patients reported their FPP-related concerns are not adequately addressed/settled during their medical appointments. Furthermore, only 30–40% of patients considered advice/information to be consistent across multiple healthcare professionals. Key online FPP-related patient discussions included disease state, adverse effects, treatment, switch behaviour and wash-out requirements.ConclusionsFemale patients who live with chronic inflammatory disease have important FPP concerns. The majority of patients, however, do not feel that their FPP concerns are adequately addressed in current clinical practice and report that they receive inconsistent advice from the various healthcare professionals who manage different aspects of their care. There is a clear need for provision of up-to-date and consistent information/support to female patients.

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