Search

Dietary or nutritional management strategies are the cornerstone of treatment for many inborn errors of metabolism (IEMs). Though a vital part of standard of care, the products prescribed for this are often not formally registered as medication. Instead, they are regulated as food or as food supplements, impacting the level of oversight as well as reimbursed policies. This scoping literature review explores the European regulatory framework relevant to these products and its implications for current clinical practice. Searches of electronic databases (PubMed, InfoCuria) were carried out, supplemented by articles identified by experts, from reference lists, relevant guidelines and case-law by the European Court of Justice. In the European Union (EU), nutritional therapy products are regulated as food supplements, food for special medical purposes (FSMPs) or medication. The requirements and level of oversight increase for each of these categories. Relying on lesser-regulated food products to treat IEMs raises concerns regarding product quality, safety, reimbursement and patient access. In order to ascertain whether a nutritional therapy product functions as medication and thus could be classified as such, we developed a flowchart to assess treatment characteristics (benefit, pharmacological attributes, and safety) with a case-based approach. Evaluating nutritional therapy products might reveal a justifiable need for a pharmaceutical product. A flowchart can facilitate systematically distinguishing products that function medication-like in the management of IEMs. Subsequently, finding and implementing appropriate solutions for these products might help improve the quality, safety and accessibility including reimbursement of treatment for IEMs.

Background A rare subset of vitamin B6 responsive seizure disorders does not respond to pyridoxine, and requires the active form of vitamin B6, pyridoxal-5′-phosphate (PLP), to maintain seizure control. Patients with PLP-responsive seizures are dependent on chronic PLP treatment, yet no licensed PLP product is available. PLP food supplements, a product category regulated less stringently than medication, may prove of insufficient effectiveness and safety. Here we describe and discuss three patient scenarios which illustrate this conundrum. Methods Medical and laboratory records were reviewed with retrospective extraction for three unrelated patients who suffered complications during treatment with PLP food supplements. Results – Two cases of PNPO deficiency and one case of PLP-dependent epileptic encephalopathy without a (genetic) diagnosis are reported. These patients are critically dependent on PLP for seizure control and have suffered complications due to insufficient quality of these food supplements during the course of treatment. Complications include the occurrence of seizures following the administration of suspected low quality PLP, inactive PLP due to light exposure, a PLP intoxication, resisting administration and post-administration vomiting as a result of the ingestion of large amounts of capsules per day. Conclusion – This case series illustrates that the reliance on food supplements as anti-seizure therapy is not without risk. The treatment of PLP-dependent seizures exemplifies that PLP is administered as medication, thus there is a clear need for licensed vitamin products of pharmaceutical quality.

Biogenic monoamine disorders are a group of inherited diseases characterized by a defect in the synthesis, transport, or degradation of catecholamines and serotonin. The phenotype mostly reflects the pattern and severity of the monoamine deficiency. Movement disorders due to cerebral dopamine deficiency are almost always prominent, mostly in the form of dystonia and/or parkinsonism. These disorders are potentially devastating yet treatable. Early diagnosis and treatment are crucial to prevent ongoing brain dysfunction. Detection of hyperphenylalaninemia in a neonate could be a good clue to the diagnosis. Final diagnosis is often based on a detailed biochemical investigation of the cerebrospinal fluid and can be confirmed by molecular analysis. Treatment is aimed at restoring neurotransmitter homeostasis using monoamine precursors, monoamine agonists, and inhibitors of monoamine degradation. It also comprises the control of hyperphenylalaninemia and the prevention of cerebral folate deficiency, when applicable.