Rding to the same exclusion criteria used in the abstract screening
Rding to the same exclusion criteria used in the abstract screening stage. The numbers ofBonnot et al. Orphanet Journal of Rare Diseases 2014, 9:65 http://www.ojrd.com/content/9/1/Page 3 ofFigure 1 Summary of literature review process.articles considered eligible after this process were: MTHFR-D (n = 12), CbS-D (n = 6), UCD (n = 15), POR (n = 49), WD (n = 51), CTX (n = 15) and NP-C (n = 31). The six previous reviews were also kept.InclusionAmong the eligible records, information on key IEM disease features as well as psychiatric manifestations was included from the following numbers of publications, per database: MTHFR-D (n = 3); CbS-D (n = 2); UCD (n = 8); POR (n = 12); WD (n = 11); CTX (n = 14) and; NP-C (n = 9). Including the six previous reviews, this brought the final total of source articles to 59.Results To understand the metabolic pathways implicated in these disorders, we will provide an explanation in the text referring directly to the cited diseases. For figures and complete presentation, we refer the reader to the KFGG website which illustrates theses pathways in detail [13].Disorders of homocysteine metabolism (DHMs)CbS-D and MTHFR-D are two key DHMs that commonly feature psychiatric signs.Key features of CbS-DHomocysteinuria due to CbS-D is characterized by the involvement of the ocular, skeletal, central nervous and vascular systems. Prevalence is estimated around 1/344 000 birth in countries were systematic search of CbS deficiency is provided for every newborn, however recent data from systematic search for CbS PF-04418948 price mutation showimportant prevalence up to 1/20 000 [14]. Two articles that addressed psychiatric symptoms and psychosis were identified [15,16]. The disease is an autosomal recessive disorder of methionine metabolism, caused by mutations in the CbS gene (21q22.3). CbS normally converts homocysteine to cystathionine in the trans-sulfuration pathway of the methionine cycle, and requires pyridoxal 5-phosphate as a cofactor. The other two cofactors involved in methionine remethylation include vitamin B12 and folic acid. Clinical diagnosis of CbS-D is confirmed by blood amino acid analysis (including total homocysteine measurement), assays of CbS enzyme activity, or screening for CbS mutations. Patients appear normal at birth but display a progressive disease course if left untreated. Eye anomalies include ectopia lentis (in 85 of cases) and high myopia. Skeletal changes include genu valgum and pes cavus, followed by dolichostenomelia, pectus excavatum or carinatum, kyphoscoliosis and osteoporosis. A Marfan-like body habitus may occur, PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26226583 with tall stature and arachnodactyly. Thromboembolism affecting both large and small arteries and veins is the most striking cause of morbidity and mortality, and affects 25 of individuals by the age of 15 years. While some individuals have a normal IQ, mental retardation is common and, when present, may progress if the disorder is left untreated. Brittle hair and livedo reticularis have also been reported.Psychiatric signs associated with CbS-DIn one of the few studies in this field, psychiatric illness was found in 51 of cases overall, with symptoms falling into four diagnostic categories: episodic depression (10 ),Bonnot et al. Orphanet Journal of Rare Diseases 2014, 9:65 http://www.ojrd.com/content/9/1/Page 4 ofchronic disorders of behavior (17 ), obsessive-compulsive disorder (5 ), and personality disorder (19 ) [15]. In the same study, aggressive behavior and other conduct disord.