Objective: Assessing the treatment with sapropterin in children less than four years. Patients: PAH deficiency patients younger than 4 years treated with sapropterin. Results: Six children less than 4 years have been treated with sapropterin. All of them but one were responsiveness. Two of them began the treatment from the newborn period and the other three began it above one year. Considering all together, the Phe (nmol/ml) mean and SD was 215,4+ 108,49; the Phe intake (mg) mean and SD was 1025+745. Children who began when they were more than one year old, the Phe intake (mg) mean and SD before sapropterin treatment was 570,14+324,83 and after treatment was 1340,96+978,86. There has been no side effects. Comments. Sapropterin treatment is a valid alternative to the treatment with a diet limited in phenylalanine in hyperphenylalaninemia in patients less than 4 years. Background: Low birth weight is associated with increased neonatal morbidity and mortality but also with life-long consequences such as cardiovascular diseases. Maternal homocysteine concentrations (tHcy) have been linked to a wide range of adverse pregnancy outcomes and could influence birth weight. We performed a systematic review and metaanalysis on the association of maternal tHcy and birth weight. Design: A literature search using Pubmed revealed 78 abstracts. Studies were eligible if information on maternal tHcy, birth weight and the association between maternal tHcy and birth weight was available. Effect estimates were converted to odds ratios with a cut-off level of birth weight <p10 for gestational age (SGA) and maternal tHcy>p90. Cystathionine beta-synthase (CBS) deficient homocystinuria (HCU) if untreated, typically results in cognitive impairment, connective tissue disturbances, and atherosclerosis and thromboembolic disease. We investigated the expression levels of 25 separate cytokines/chemokines in both a transgenic mouse model of HCU and human subjects with the disease. HCU mice exhibited highly significant inductions of the pro-inflammatory cytokines Il-1alpha, Il-1beta and TNF-alpha which were normalized or significantly lowered by treatment with either betaine or the antioxidant amino sulfonic acid taurine. In untreated/poorly compliant human subjects with HCU, we observed constitutive induction of multiple pro-inflammatory cytokines (IL-1alpha, IL-6, TNF-alpha, Il-17 and IL-12(p70)) and chemotactic chemokines (fractalkine, MIP-1alpha and MIP-1beta) compared to normal controls. The expression levels of anti-inflammatory cytokines were normal in both HCU mice and humans with the disease. In human subjects, conventional therapy lead to either normalization or significant reduction of all of the proinflammatory cytokines and chemokines investigated.We conclude that HCU is a disease of oxidative stress induced chronic inflammation and that aberrant cytokine expression has the potential to contribute to multiple aspects of pathogenesis. Our findings indicate that antioxidant and anti-inflammatory strategies could serve as useful adjuvant therapies for this disease. Misfolding of mutant proteins is a common pathogenic mechanism in many genetic diseases including phenylketonuria. Since misfolding of mutant phenylalanine hydroxylase enzymes is successfully targeted by sapropterin administration we explored whether misfolding plays a role in cystathionine beta-synthase (CBS) deficiency and whether it can be modulated by chaperones.