Glutaric aciduria type 1: Diagnosis, clinical features and long-term outcome in a large cohort of 34 Irish patients.

Glutaric aciduria type 1 (GA1) is a rare neurometabolic disorder that can lead to encephalopathic crises and severe dystonic movement disorders. Adherence to strict dietary restriction, in particular a diet low in lysine, carnitine supplementation and emergency treatment in pre-symptomatic patients diagnosed by high-risk screen (HRS) or newborn screen (NBS) leads to a favourable outcome. We present biochemical and clinical characteristics and long-term outcome data of 34 Irish patients with GA1 aged 1-40 years. Sixteen patients were diagnosed clinically, and 17 patients by HRS, prior to introduction of NBS for GA1 in the Republic of Ireland in 2018. One patient was diagnosed by NBS. Clinical diagnosis was at a median of 1 year (range 1 month to 8 years) and by HRS was at a median of 4 days (range 3 days to 11 years). 14/18 (77.8%) diagnosed by HRS or NBS had neither clinical manifestations nor radiological features of GA1, or had radiological features only, compared to 0/16 (0%) diagnosed clinically (p < 0.001). Patients diagnosed clinically who survived to school-age were more likely to have significant cerebral palsy and dystonia (7/11; 63.6% vs. 0/13; 0%, p < 0.001). They were less likely to be in mainstream school versus the HRS group (5/10; 50% vs. 12/13; 92.3%; p = 0.012). Clinical events occurring after 6 years of age were unusual, but included spastic diplegia, thalamic haemorrhage, Chiari malformation, pituitary hormone deficiency and epilepsy. The exact aetiology of these events is unclear.

The risk of malnutrition in children with autism spectrum disorder.

A 9-year-old boy presented with a 2-day history of vomiting, ataxia and reduced consciousness. He had vomited intermittently in the two preceding months, without headaches, visual disturbance or early morning symptoms. He had autism spectrum disorder, and restricted eating since aged 2 years, eating only corn-crisps, Rich Tea biscuits and chips (French fries), and drinking Coca-Cola (containing 10% glucose; figure 1). Recently a dietician had prescribed a multivitamin.

Inhibition of ex vivo erythropoiesis by secreted and haemozoin-associated Plasmodium falciparum products.

It has been estimated that up to a third of global malaria deaths may be attributable to malarial anaemia, with children and pregnant women being those most severely affected. An inefficient erythropoietic response to the destruction of both infected and uninfected erythrocytes in infections with Plasmodium spp. contributes significantly to the development and persistence of such anaemia. The underlying mechanisms, which could involve both direct inhibition of erythropoiesis by parasite-derived factors and indirect inhibition as a result of modulation of the immune response, remain poorly understood. We found parasite-derived factors in conditioned medium (CM) of blood-stage Plasmodium falciparum and crude isolates of parasite haemozoin directly to inhibit erythropoiesis in an ex vivo model based on peripheral blood haematopoietic stem cells. Erythropoiesis-inhibiting activity was detected in a fraction of CM that was sensitive to heat inactivation and protease digestion. Erythropoiesis was also inhibited by crude parasite haemozoin but not by detergent-treated, heat-inactivated or protease-digested haemozoin. These results suggest that the erythropoiesis-inhibiting activity in both cases is mediated by proteins or protein-containing biomolecules and may offer new leads to the treatment of malarial anaemia.