Autism spectrum disorders (ASDs) are a major health problem because of their high prevalence in the general population. The pathophysiology of ASD remains unclear, although genetic defects may be detected in 10-20% of affected patients. Among these cases, the prevalence of inherited metabolic disorders (IMD) has not been extensively evaluated. IMDs responsible for ASDs are usually identified via clinical manifestations such as microcephaly, dysmorphic features, convulsions, and hepatosplenomegaly. Infrequently, patients with no additional clinical symptoms suggestive of an IMD may be diagnosed as having an idiopathic ASD. High consanguinity rates have resulted in an increased prevalence of IMDs in the Turkish population. The aim of this study was to explore the benefits of systematic screening for IMD among Turkish patients with ASDs. In our study, data were retrospectively collected for 778 children with ASDs. In all cases, the metabolic investigations included an arterial blood gas analysis, serum ammonia and lactate levels, a quantitative plasma amino acid analysis, a whole blood acylcarnitine profile via tandem mass spectrometry and a urine organic acid profile. Urinary glycosaminoglycan levels and homocysteine levels were screened in selected cases; 300 of the 778 patients with ASDs whose physical and metabolic investigations were complete and met this study's criteria were enrolled. Among the 300 children with autism, IMD were diagnosed in nine patients as follows: two patients were diagnosed with phenylketonuria, and one patient was diagnosed with partial biotinidase deficiency; one patient was diagnosed with mucopolysaccharidosis type III, and one patient was diagnosed with classical homocystinuria; one patient was diagnosed with glutaric acidemia type 1, and one patient was diagnosed with short chain acyl-CoA dehydrogenase deficiency; one patient was diagnosed with argininemia, and one patient was diagnosed with L-2-hydroxyglutaric aciduria.

Background Cerebrotendinous xanthomatosis (CTX) is a rare, chronic, progressive, neurodegenerative disorder requiring life-long care. Patients with CTX often experience a diagnostic delay. Although early diagnosis and treatment initiation can improve symptoms and prognosis, a standardised approach to diagnosis, treatment and management of patients is not yet established. Aim To assess expert opinion on best care practices for patients with CTX using a modified Delphi method. Methods A multidisciplinary group of healthcare professionals with expertise in CTX responded to a 3-round online questionnaire (n = 10 in Rounds 1 and 2; n = 9 in Round 3), containing questions relating to the diagnosis, treatment, monitoring, multidisciplinary care and prognosis of patients with CTX. Determination of consensus achievement was based on a pre-defined statistical threshold of ≥ 70% Delphi panellists selecting 1–2 (disagreement) or 5–6 (agreement) for 6-point Likert scale questions, or ≥ 70% Delphi panellists choosing the same option for ranking and proportion questions. Results Of the Round 1 (n = 22), Round 2 (n = 32) and Round 3 (n = 26) questions for which consensus was assessed, 59.1%, 21.9% and 3.8% reached consensus, respectively. Consensus agreement that genetic analyses and/or determination of serum cholestanol levels should be used to diagnose CTX, and dried bloodspot testing should facilitate detection in newborns, was reached. Age at diagnosis and early treatment initiation (at birth, where possible) were considered to have the biggest impact on treatment outcomes. All panellists agreed that chenodeoxycholic acid (CDCA) is a lifetime replacement therapy which, if initiated early, can considerably improve prognosis as it may be capable of reversing the pathophysiological process in CTX. No consensus was reached on the value of cholic acid therapy alone. Monitoring patients through testing plasma cholestanol levels and neurologic examination was recommended, although further research regarding monitoring treatment and progression of the disease is required. Neurologists and paediatricians/metabolic specialists were highlighted as key clinicians that should be included in the multidisciplinary team involved in patients’ care. Conclusions The results of this study provide a basis for standardisation of care and highlight key areas where further research is needed to inform best practices for the diagnosis, treatment and management of patients with CTX.

Continious renal replacement therapy (CRRT) is a well recognizied treatment of choice in acute renal failure, however CRRT became a preferred treatment of metabolic emergencies with high leucine and ammonia levels like Maple syrup urine disease (MSUD). MSUD is a rare metabolic disorder caused by deficiency in the activity of the branched-chain a-ketoacid dehydrogenase complex. The toxic accumulation of branched chain amino acids during acute metabolic decompensation is associated with the appearance of permanent neurological symptoms. Four patients were admitted to our pediatric intensive care department with complains of poor feeding, vomitting, irratibility and coma. Physical examination of the neonates were similar having stupor, hypotonia and depressed newborn reflexes. The leucine levels were between 930-4400 μmol/L. The diagnosis of MSUD was confirmed in all four. They were treated successfully with high flow CRRT having the rates were between 4120 ml/h/1.73m2 and 9830 ml/h/1.73m2. Early treatment is essential to prevent neurotoxicity and death. CRRT is a choice of treatment in metabolic crisis of MSUD. Herein, we report the successful treatment of acute metabolic decompensation of MSUD with CRRT in 4 neonates.

Background: Argininemia is an autosomal recessive urea cycle disorder (UCD). Unlike other UCD, hyperammonemia is rarely seen. Patients usually present in childhood with neurological symptoms. Uncommon presentations like neonatal cholestasis or cirrhosis have been reported. Although transient elevations of liver transaminases and coagulopathy have been reported during hyperammonemia episodes, a permanent coagulopathy has never been reported. Methods: In this retrospective study, coagulation disturbances are examined in 6 argininemia patients. All of the patients were routinely followed up for hepatic involvement due to argininemia. Laboratory results, including liver transaminases, albumin, prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), and clotting factor levels, were assessed in all of the patients. Results: All of the patients had a prolonged PT and an increased INR, while none of the patients had a prolonged aPTT. Five patients had slightly elevated liver transaminases. A liver biopsy was performed in 1 patient but neither cirrhosis nor cholestasis was documented. Five of the 6 patients had low factor VII and factor IX levels, while other clotting factors were normal. Conclusions: Argininemia patients should be investigated for coagulation disorders even if there is no apparent liver dysfunction or major bleeding symptoms.

Nitisinone treatment is effective and improves both short- and long-term prognosis of HT1. Early diagnosis on newborn screening is needed because delay in treatment increases the risk of the persistence of hepatic disease and HCC. Interruption of the drug can lead to re-occurrence of hepatocellular damage and neurological crisis. Increased α-fetoprotein and new hypoechoic nodule formation are the warning signs for HCC.

Background: The prognosis of phenylketonuria (PKU) in terms of neurocognitive outcome is directly related to lifelong phenylalanine (Phe) levels and adherence to treatment. Monitoring and treatment of PKU patients can be complicated in challenging circumstances as pandemics. This study aims to evaluate the impact of telemedicine for monitoring and treatment of PKU patients on metabolic outcome during coronavirus disease-19 (COVID-19) outbreak. Materials and Methods: Patients who were diagnosed as PKU and treated with low Phe diet, tetrahydrobiopterin (BH4), or BH4 adjunct with low Phe diet were enrolled. Study period was divided into two periods: prepandemic period wherein patients were followed up in outpatients' clinic and during pandemic wherein telemedicine was used. Demographic findings, laboratory results, and therapy responses were reviewed retrospectively and compared between the two periods. All procedures were in accordance with the ethical standards of the local ethical committee of Cerrahpasa Medical Faculty (17/11/2020-151640) and with the Helsinki Declaration of 1975, as revised in 2013. Results: Ninety-three (n = 93) patients were enrolled to this study. The ratio of the samples with Phe levels in the recommended ranges was found to be statistically higher during the pandemic wherein an online monitoring system was used in all treatment modalities (p < 0.05). The decrease in Phe washout frequency was statistically significant during the pandemic in the low Phe diet group (p < 0.05). Considering the relationship between Phe tolerance before and during the pandemic, a significant increase in Phe tolerance was noted during the pandemic in the low Phe diet group (p < 0.05). Conclusions: Telemedicine can be an appropriate and effective monitoring option for PKU patients during the COVID-19 pandemic.

Aim Mucopolysaccharidosis type III B (MPS IIIB) is an autosomal recessive lysosomal storage disease caused by mutations in the NAGLU gene which codes the lysosomal enzyme alpha- N -acetylglucosaminidase. The major symptoms of the disease are cognitive and neurological defects. In this study, the molecular spectrums of 13 MPS IIIB patients were evaluated. Material and methods Thirteen MPS IIIB patients from 11 families were included in this study. All patients were both clinically and molecularly diagnosed. NAGLU gene sequencing was performed using a next generation sequencing platform (Illumina MiSeq). Demographic, clinical and laboratory findings of the patients were obtained via the hospital records. Results Ten different mutations from the 13 MPS IIIB patients were identified. Eight of the 10 mutations were missense, one was splice site, and one large deletion was also observed. Two mutations c.509G>T (p.Gly170Val) and c.700C>G (p.Arg234Gly) have been defined for the first time in this study. Conclusion Our study expanded the mutation spectrum of the NAGLU gene thereby contributing to the improved genetic counselling of MPS IIIB patients. Confirming the literature, missense mutations were also found to be the most common NAGLU mutations in our study.

Nitisinone (2-[2-nitro-4-trifluoromethylbenzoyl]cyclohexane-1,3-dione), an effective triketone herbicide, is a potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase, the second enzyme in the tyrosine catabolic pathway. Since 1992, the drug has become an effective pharmacological treatment for hereditary tyrosinemia type 1 (HT1). Nitisinone can prevent the development of liver disease, reverse and prevent the renal tubular dysfunction, severe neurological crisis and cardiomyopathy and significantly reduce the risk of developing hepatocellular carcinoma in HT1 patients. Its mode of action, with few side effects reported, make the drug a potential candidate for the treatment of other disorders of tyrosine metabolism, including alkaptonuria, with successful reduction in homogentisic acid production to prevent long-term complications. Nitisinone could also be a promising agent in the treatment of tumors with active tyrosine metabolic pathways. In this review, we discuss the effects of nitisinone for various tyrosine pathway disorders.