Clinical, biochemical, and molecular insights into Cerebrotendinous Xanthomatosis: A nationwide study of 100 Turkish individuals.

OBJECTIVE: Cerebrotendinous xanthomatosis (CTX) is an inherited metabolic disorder characterized by progressive neurologic and extraneurologic findings. The aim of this retrospective, descriptive study was to explore the time of presentation and diagnosis, and to expand the phenotype and genotype of CTX, based on a nationwide and comprehensive series of patients in Turkey. METHODS: The demographic, clinical, biochemical and genotypic characteristics of the CTX patients were reviewed. Data on molecular analysis, age of onset and diagnosis, diagnostic delay, neurologic and extraneurologic symptomatology, results of plasma cholestanol levels, brain magnetic resonance imaging and electromyography at the time of diagnosis were reviewed. RESULTS: 100 confirmed CTX patients from 72 families were included. The mean age at diagnosis was 28.16 ± 14.28 years, and diagnostic delay was 18.39 ± 13.71 years. 36 patients were diagnosed in childhood. Frequency of intention tremor (p = 0.069), peripheral neuropathy (p = 0.234) and psychiatric manifestations (p = 0.396) did not differ between two groups, demonstrating the high rate in pediatric patients. Three adult patients showed a milder phenotype without neurologic involvement. Seven patients had normal plasma cholestanol levels despite neurological impairment. Sequencing of the CYP27A1 gene revealed 25 different variants, with a novel c.671_672del variant not previously described in literature. CONCLUSION: Based on the observations of this Turkish CTX cohort, it is emphasized that the true prevalence of CTX is probably underestimated and that it has a wide spectrum of clinical phenotypes even without neurological impairment. In children, abnormal cerebellar findings, peripheral neuropathy and psychiatric findings associated with intellectual disability have been suggested as warning signs to avoid diagnostic delay. In cases of clinical suspicion, molecular analysis is recommended despite normal plasma cholestanol levels, as severe neurologic involvement may occur in CTX patients without elevated cholestanol levels.

Evaluation of patients with phenylalanine metabolism disorder: a single center experience.

AIM: The aim is to evaluate the clinical, demographic and laboratory data of the patients we followed up with phenylalanine metabolism disorder. MATERIALS AND METHODS: In this study, patients with phenylalanine metabolism disorder who applied to Bursa Uludag University Faculty of Medicine, Department of Pediatrics, Pediatric Metabolism Department between 2011 and 2021 were retrospectively examined. The files of 397 patients who were followed up in our pediatric metabolism outpatient clinic and were found to have phenylalanine metabolism disorder by plasma phenylalanine level and molecular genetic analysis were evaluated. RESULTS: According to the highest plasma phenylalanine levels at admission, mild hyperphenylalaninemia phenotype constituted the largest group of 397 patients with 282 cases (71.1%), while the least common phenotype was malignant phenylketonuria (BH4 metabolism disorder) with four patients (1.0%). The number of patients with classical phenylketonuria was 90 (22.6%). 61 (62.8%) of 97 phenylalanine metabolism disorder cases who underwent BH4 loading test had a response. The mean phenylalanine level of the patients was 3.62 ± 1.31 mg/dL in mild hyperphenylalaninemia, 7.98 ± 3.99 mg/dL in mild phenylketonuria and 11.71 ± 4.39 mg/dL in classical phenylketonuria. While 241 (76%) of 317 patients younger than 8 years old were in the well-controlled group, 76 (24%) were in the poorly-controlled group. While 41 (53.9%) of 76 patients older than 8 years of age were in the well-controlled group, 35 (46.1%) were in the poorly-controlled group. CONCLUSIONS: In our study, the largest patient group consisted of patients with mild hyperphenylalaninemia, and the least common phenotype was mild phenylketonuria.

An Unusual Case of LCHAD Deficiency Presenting With a Clinical Picture of Hemophagocytic Lymphohistiocytosis: Secondary HLH or Coincidence?

There are published reports stating that some of the congenital metabolic diseases, such as lysinuric protein intolerance, multiple sulphatase deficiency, galactosemia, Gaucher disease, Pearson syndrome, and galactosialidosis, might lead to secondary hemophagocytic lymphohistiocytosis (HLH). However, to date, to our knowledge, the long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency has never been investigated among patients with HLH. Here, we report on a patient who was referred to our institution for a differential diagnosis of pancytopenia, liver failure, and rhabdomyolysis. The patient was diagnosed with HLH. Further investigation revealed an underlying diagnosis of the LCHAD deficiency. Our case was reported to contribute to the literature, as well as the HLH clinic, emphasizing the consideration of LCHAD deficiency, especially in 1 to 6 months' old infants with laboratory findings of hypoglycemia, metabolic acidosis, and elevated creatine kinase.

A Turkish Patient With Succinyl-CoA:3-Oxoacid CoA Transferase Deficiency Mimicking Diabetic Ketoacidosis

Abstract Succinyl-CoA:3-oxoacid CoA transferase (SCOT) deficiency is an autosomal recessive disorder of ketone body utilization that is clinically characterized with intermittent ketoacidosis crises. We report here the second Turkish case with SCOT deficiency. She experienced 3 ketoacidotic episodes: The first ketoacidotic crisis mimicked diabetic ketoacidosis because of the associated hyperglycemia. Among patients with SCOT deficiency, the blood glucose levels at the first crises were variable, and this case had the highest ever reported blood glucose level. She is a compound heterozygote with 2 novel mutations, c.517A>G (K173E) and c.1543A>G (M515V), in exons 5 and 17 of the OXCT1 gene, respectively. In patient's fibroblasts, SCOT activity was deficient and, by immunoblot analysis, SCOT protein was much reduced. The patient attained normal development and had no permanent ketosis. The accurate diagnosis of SCOT deficiency in this case had a vital impact on the management strategy and outcome.