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Objectives: The present study describes clinical, biochemical, molecular genetic data, current treatment strategies and follow-up in nine patients with tetrahydrobiopterin (BH4) deficiency due to various inherited genetic defects., Methods: We analyzed clinical, biochemical, and molecular data of nine patients with suspected BH4 deficiency. All patients were diagnosed at Ege University Faculty of Medicine in Izmir, Turkey and comprised data collected from 2006 to 2019. The diagnostic laboratory examinations included blood phenylalanine and urinary or plasma pterins, dihydropteridine reductase (DHPR) enzyme activity measurement in dried blood spots, folic acid and monoamine neurotransmitter metabolites in cerebrospinal fluid, as well as DNA sequencing., Results: Among the nine patients, we identified one with autosomal recessive GTP cyclohydrolase I (ar GTPCH) deficiency, two with 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency, three with sepiapterin reductase (SR) deficiency, and three with DHPR deficiency. Similar to previous observations, the most common clinical symptoms are developmental delay, intellectual disability, and movement disorders. All patients received treatment with l-dopa and 5-hydroxytryptophan, while only the ar GTPCH, the PTPS, and one DHPR deficient patients were supplemented in addition with BH4. The recommended dose range varies among patients and depends on the type of disease. The consequences of BH4 deficiencies are quite variable; however, early diagnosis and treatment will improve outcomes., Conclusions: As BH4 deficiencies are rare group of treatable neurometabolic disorders, it is essential to diagnose the underlying (genetic) defect in newborns with hyperphenylalaninemia. Irreversible brain damage and progressive neurological deterioration may occur in untreated or late diagnosed patients. Prognosis could be satisfying in the cases with early diagnose and treatment., Competing Interests: Ayse Ergul Bozaci, Esra Er, Havva Yazici, Ebru Canda, Sema Ucar Kalkan, Merve Saka Guvenc, Cenk Eraslan, Huseyin Onay, Sara Habif, Beat Thony, Mahmut Coker declare that they have no conflict of interest., (© 2021 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.)

Unlabelled: Argininosuccinate lyase deficiency (ASLD) is a urea cycle disorder (UCD) treated with dietary adjustment and nitrogen scavenging agents. "Pheburane(®)" is a new tasteless and odour-free formulation of sodium phenylbutyrate, indicated in the treatment of UCD.A male patient diagnosed with ASLD was put on treatment with the new formulation of sodium phenylbutyrate (granules) for a period of one year, at 500 mg/kg orally in 3 intakes/day. Plasma glutamine, arginine, citrulline, argininosuccinate, serum sodium, potassium, liver function tests and urine orotate all remained unchanged over this period. There was no difference in mean ammonia levels before and after treatment, and no hyperammonemia episode occurred during treatment with Pheburane(®). An improvement in a measurement of quality of life (QOL) was noted after treatment with Pheburane(®)., Conclusion: Good metabolic control and improved QOL were achieved throughout the treatment period.

Dorfman-Chanarin syndrome is a rare, autosomal recessive inherited lipid storage disease with congenital ichthyotic erythroderma due to an acylglycerol recycling defect. It is characterized by accumulation of neutral lipids in different tissues. Liver, muscle, ear, eye, and central nervous system are generally involved, so we presented a patient with severe ichthyosis, lipid vacuoles in neutrophils, and multiorgan involvement including a very rare complication, renal involvement. A 7-month-old girl was presented with frequent respiratory infection, congenital ichthyotic erithroderma and suspicion for immune deficiency. On her physical examination hepatomegaly, developmental delay, palmar and plantar hyperkeratosis and increased deep tendon reflexes with clonus and high tonus were found. Laboratory investigations revealed elevation at transaminases levels, hypoalbuminemia, hypergammaglobulinemia, presence of autoantibodies and eosinophilia. Vacuolization in leukocytes confirmed Dorfman-Chanarin syndrome, whereas no mutation at RAG1-2 and ARTEMIS genes ruled-out immune deficient status of the patient. At the age of eight months the patient died from severe renal failure. Her necropsies demonstrated microvesicular lipid accumulation not only at the liver but also at the renal species. The variability of involvement of different systems in Dorfman-Chanarin syndrome is well described, however the renal findings has not been reported previously at the literature.

C-reactive protein is an acute phase protein widely used as an indicator of infectious or inflammatory conditions. Traditionally it has been used as an adjunctive test for inflammation and as a marker of disease activity. Though sensitive, its nonspecific nature imposes limitation on its clinical use. Currently C-reactive protein is used in the management of chorioamnionitis, preterm premature rupture of membranes, pelvic inflammatory disease, and urinary tract infection. Interestingly, several obstetric conditions such as pre-eclampsia and gestational diabetes are now known to have an underlying inflammatory basis and there is an emerging role of C-reactive protein testing in managing these diseases. Additionally C-reactive protein testing has an established place in management of several acute abdominal conditions. The aim of this paper is to review the place of C-reactive protein in modern obstetric and gynecological practice.

Reasons for Performing Study: Analgesia of the palmar digital (PD) nerves has been demonstrated to cause analgesia of the distal interphalangeal (DIP) joint as well as the sole. Because the PD nerves lie in close proximity to the navicular bursa, we suspected that that analgesia of the navicular bursa would anaesthetise the PD nerves, which would result in analgesia of the DIP joint., Objectives: To determine the response of horses with pain in the DIP joint to instillation of local anaesthetic solution into the navicular bursa., Methods: Lameness was induced in 6 horses by creating painful synovitis in the DIP joint of one forefoot by administering endotoxin into the joint. Horses were videorecorded while trotting, before and after induction of lameness, at three 10 min intervals after instilling 3.5 ml local anaesthetic solution into the navicular bursa and, finally, after instilling 6 ml solution into the DIP joint. Lameness scores were assigned by grading the videorecorded gaits subjectively., Results: At the 10 and -20 min observations, median lameness scores were not significantly different from those before administration of local anaesthetic solution into the navicular bursa (P > or = 0.05), although lameness scores of 3 of 6 horses improved during this period, and the 20 min observation scores tended toward significance (P = 0.07). At the 30 min observation, and after analgesia of the DIP joint, median lameness scores were significantly improved (P < or = 0.05)., Conclusions: These results indicate that pain arising from the DIP joint can probably be excluded as a cause of lameness, when lameness is attenuated within 10 mins by analgesia of the navicular bursa., Potential Relevance: Pain arising from the DIP joint cannot be excluded as a cause of lameness when lameness is attenuated after 20 mins after analgesia of the navicular bursa.

We hypothesised that analgesia of the navicular bursa is not selective for the navicular apparatus; and that solar pain in some horses can be temporarily abolished or attenuated by analgesia of the navicular bursa. To test this hypothesis, we caused lameness in horses by inducing pain in the dorsal margin or the angles of the sole and then evaluated the ability of a local analgesic solution administered into the navicular bursa to attenuate lameness. The response of horses with solar pain in the dorsal or palmar aspect of the foot to 3.5 ml local analgesic solution administered into the navicular bursa was examined. Lameness was induced in 6 horses by creating solar pain in the dorsal aspect of one forefoot and, at another time, the palmar aspect of the other forefoot, with set-screws inserted into a custom-made shoe. Horses were videotaped trotting before and after application of set-screws and after administering 3.5 ml local analgesic solution into the navicular bursa. Lameness scores were assigned by examining videotaped gaits. Scores were significantly lower (P<0.05) for all horses with set-screws applied to the dorsal margin of the sole after administration of local analgesic solution into the navicular bursa. In conclusion, analgesia of the navicular bursa was less effective in desensitising the angles of the sole than in desensitising the dorsal margin of the sole. Pain arising from the sole should not be excluded as a cause of lameness when lameness is attenuated by analgesia of the navicular bursa.

The response of horses, with solar pain in the dorsal or palmar aspect of the foot, to 6 or 10 ml local analgesic solution administered into the distal interphalangeal (DIP) joint was examined. Lameness was induced in 7 horses by creating solar pain in the dorsal aspect of one forefoot and, at another time, the palmar aspect of the other forefoot with set-screws inserted into a custom-made shoe. Horses were videotaped trotting before and after application of set-screws and, in separate trials, after 6 or 10 ml local analgesic solution was administered into the DIP joint. Lameness scores were assigned by examining videotaped gaits. Scores were significantly lower (P < 0.05) for horses with set-screws applied to the angles of the sole and receiving 10 ml, but not 6 ml, local analgesic solution into the DIP joint. Scores were significantly lower (P < 0.05) for all horses with set-screws in the dorsal margin of the sole receiving either volume of local analgesic solution. Analgesia of the DIP joint was less effective in desensitising the angles of the sole than in desensitising the dorsal margin of the sole, and 10 ml local analgesic solution was more effective than 6 ml in desensitising these regions. The response of horses with solar pain to local analgesic solution in the DIP joint was influenced by the volume administered and the region of sole affected.

Odd-chain (C15 and C17) fatty acids have been reported to accumulate in tissues and body fluids of patients with propionic and methylmalonic acidaemia. We investigated the occurrence of these substances in amniotic fluid samples. The odd-chain fatty acid levels (expressed as the percentage of total C12-C20 fatty acids) in eight control samples ranged from 3.7 to 12.5 per cent. Three samples from affected propionic acidaemia pregnancies had values of 15.3-22.9 per cent; one methylmalonic acidaemia sample had a normal level of 9.3 per cent. These results supply further evidence of the prenatal accumulation of odd-chain fatty acids in propionic acidaemia.

Total plasma odd-numbered long-chain fatty acids were analysed in patients with methylmalonic acidaemia (vitamin B12-responsive and unresponsive), combined methylmalonic acidaemia/homocystinuria (CblC), propionic acidaemia (both neonatal-onset and late-onset), biotinidase deficiency and holocarboxylase synthase deficiency, as well as in hospital controls. Total odd-numbered long-chain fatty acids (C15:0, C17:1 and C17:0) were expressed as a percentage of total C12-C20 fatty acids. Control values were 0.72% +/- 0.31% (n = 12). Normalization of the percentage of odd-chain fatty acids occurred in all vitamin-responsive patients, following the institution of vitamin treatment. In general the neonatal-onset propionic acidaemia and B12-unresponsive methylmalonic acidaemia patients had the highest plasma odd-chain fatty acid concentrations, which correlated with the clinical condition but not with the urinary excretion of methylcitrate or methylmalonate. Plasma odd-chain fatty acid concentrations and methylmalonate excretions in CblC patients reacted very well to vitamin B12 treatment, but with no clinical response. Measurement of plasma odd-chain fatty acids is of no value for the monitoring of defects of biotin metabolism.