Exploring metabolic alterations in PYCR2 deficiency: Unveiling pathways and clinical presentations of hypomyelinating leukodystrophy 10.

Proline-5-carboxylate reductase 2, encoded by PYCR2 gene, is an enzyme that catalyzes the last step of proline synthesis from pyrroline-5-carboxylate synthetase to proline. PYCR2 gene defect causes hypomyelinating leukodystrophy 10. Up until now, to our knowledge around 38 patients with PYCR2 defect have been reported. Herein, we describe clinical, neuroradiological, biochemical findings, and metabolomic profiling of three new genetically related cases of PYCR2 defects from a large family. Cerebrospinal fluid (CSF) amino acid levels were measured and untargeted metabolomic profiling of plasma and CSF were conducted and evaluated together with the clinical findings in the patients. While plasma and CSF proline levels were found to be totally normal, untargeted metabolomic profiling revealed mild increases of glutamate, alpha-ketoglutarate, and l-glutamate semialdehyde and marked increases of inosine and xanthine. Our findings and all the previous reports suggest that proline auxotrophy is not the central disease mechanism. Untargeted metabolomics point to mild changes in proline pathway and also in purine/pyrimidine pathway.

A Rare Treatable Cause of Cardiomyopathy: Primary Carnitine Deficiency.

Introduction: Primary carnitine deficiency (PCD) is a rare autosomal recessive disorder caused by loss of function mutations in the solute carrier family 22 member 5 (SLC22A5) gene that encodes a high-affinity sodium-ion-dependent organic cation transporter protein (OCTN2). Carnitine deficiency can result in acute metabolic decompensation or, in a more insidious presentation, cardiomyopathy. Cardiomyopathy associated with PCD often presents with life-threatening heart failure. This presentation also usually includes skeletal muscle myopathy. Early recognition of this disorder and treatment with carnitine can avoid life-threatening complications related to cardiomyopathy. Case Presentation: Herein, we present a 10-month-old male patient with PCD, which was diagnosed while investigating the etiology of dilated cardiomyopathy and confirmed by molecular genetic analysis. Conclusion: Homozygous c.254_265 insGGCTCGCCACC (p.I89Gfs) pathogenic variant of the SLC22A5 gene was detected. With oral L-carnitine supplementation, the free carnitine level increased up to 14 µmol/L and the symptoms disappeared. LVEF increased by 45-70%. We would like to emphasize that this problem is a combination of the metabolic decompensation and the cardiac phenotypes, which are usually separated to either phenotype.

Mitochondrial phosphate-carrier deficiency mimicking infantile-onset Pompe disease.

The mitochondrial phosphate carrier is critical for adenosine triphosphate synthesis by serving as the primary means for mitochondrial phosphate import across the inner membrane. Variants in the SLC25A3 gene coding mitochondrial phosphate carrier lead to failure in inorganic phosphate transport across mitochondria. The critical dependence on mitochondria as an energy source is especially evident in tissues with high-energy demands such as the heart, muscle; defects in the mitochondrial energy production machinery underlie a wide range of primary mitochondrial disorders that present with cardiac and muscle diseases. The characteristic clinical picture of a prominent early-onset hypertrophic cardiomyopathy and lactic acidosis may be an indication for analysis of the SLC25A3 gene. Here, described a patient with suspicion of infantile Pompe disease due to involvement of heart and muscle and high-level of plasma creatinine kinase but finally diagnosed mitochondrial phosphate-carrier deficiency.

Evaluation of clinical, laboratory, and molecular genetic features of patients with biotinidase deficiency.

Biotinidase deficiency (BD) is an autosomal recessive inherited metabolic disorder which results from the inability of biotin-dependent carboxylase enzymes to function due to the release and absorption of biotin, leading to neurological and cutaneous findings. In the present study, evaluation of demographic characteristics, clinical findings, laboratory results, molecular genetic characteristics, and genotype-phenotype correlations of cases with BD. Two hundred forty-seven cases were included in the study who were admitted to the Department of Pediatric Metabolism of Ankara Bilkent City Hospital after being identified with potential BD through the Newborn Screening Program (NBS), during family screening or based on suspicious clinical findings, or following the detection of a pathogenic variant in a BTD genetic analysis during the period of October 2020 and February 2022. The medical files of the cases were reviewed retrospectively. An analysis of the admission routes of all cases to our clinic revealed 89.5% NBS, 5.7% family screening, and 4.9% suspicious clinical findings suggestive of BD. Complete enzyme deficiency was identified in 19.8%, partial enzyme deficiency in 55.1%, and heterogenous enzyme deficiency in 9.7%. The most common pathogenic variants were c.1270G > C (p.Asp424His), c.410G > A (p.Arg137His), and c.38_44delGCGCTGinsTCC (p.Cys13Phefs*36) in BTD gene. The c.1270G > C variant was most common in patients with cutaneous symptoms. The c.410G > A and c.38_44delGCGCTGinsTCC variants were more common in the patients with neurological symptoms. The mean activity level in patients with the c.1270G > C homozygous variant was statistically significantly higher than the mean activity level in the c.1270G > C compound heterozygous patients and the activity level of patients without the c.1270G > C variant. The mean activity level in c.410G > A homozygous patients was statistically significantly lower than the mean activity level of the c.410G > A compound heterozygous patients and the activity level of patients without the c.410G > A variant. In the course of our study, four new pathogenic variants were detected, namely: c.190G > A (p.Glu64Lys), c.249 + 5G > T, c.228delA (p.Val77*), and c.682A > G (p.Ile228Val).     Conclusions: The present study has determined the clinical and genetic spectrum of a large group of patients with BD in a single center. The frequent mutations in our study were similar to those reported in literature, and four novel variants were also described. What is Known: • Biotinidase deficiency is an autosomal recessive, treatable inborn error of metabolism. Two hundred ninety-four pathogenic variants in the BTD gene have been identified and the c.1270G > C variant is the most frequent BTD gene mutation in both Turkey and around the world. What is New: • Four new pathogenic variants (c.190G > A, p.Glu64Lys; c.249 + 5G > T; c.228delA, p.Val77*; and c.682A > G, p.Ile228Val) have been identified. It is believed that the c.38_44delGCGGCTGinsTCC variant is more commonly seen in individuals with ocular issues; however, further genotype-phenotype correlations are needed.

Assessment of the diagnosis, treatment, and follow-up of a group of Turkish pediatric glycogen storage disease type 1b patients with varying clinical presentations and a novel mutation.

OBJECTIVES: Glycogen storage disease (GSD) type 1b is a multisystemic disease in which immune and infectious complications are present, different from GSD type 1a. Treatment with granulocyte-colony stimulating factor (G-CSF) is often required in the management of neutropenia and inflammatory bowel disease. Recently, an alternative treatment option to G-CSF has been preferred, like empagliflozin. To report on the demographics, genotype, clinical presentation, management, and complications of pediatric patients with glycogen storage disease type 1b (GSD 1b). METHODS: A retrospective analysis of the clinical course of eight patients with GSD type 1b whose diagnosis was confirmed by molecular testing. RESULTS: The mean age at referral was four months. The diagnosis of GSD 1b was based on clinical and laboratory findings and supported by genetic studies. One patient presented with an atypical clinical finding in the form of hydrocephalus at the time of first admission. The first symptom was abscess formation on the scalp due to neutropenia in another patient. Other patients had hypoglycemia at the time of admission. All patients presented suffered from neutropenia, which was managed with G-CSF, except one. Hospitalizations for infections were frequent. One patient developed chronic diarrhea and severe infections, which have been brought under control with empagliflozin. CONCLUSIONS: Neutropenia is an essential finding in GSD 1b and responsible for complications. The coexistence of hypoglycemia and neutropenia should bring to mind GSD 1b. Empagliflozin can be a treatment option for neutropenia, which is resistant to G-CSF treatment.

Does glutaric aciduria type 1 affect hearing function?

This study aimed to evaluate audiological findings among patients with glutaric aciduria type 1 (GA-1). We used a large test battery for the audiological evaluation of 17 individuals with GA-1 (the study group) and 20 healthy individuals (the control group). Conventional audiometry (0.125-8 kHz), distortion product otoacoustic emissions (DPOAEs) (1, 1.5, 2, 3, 4, 6, and 8 kHz), contralateral suppression of otoacoustic emissions, and auditory brainstem response (ABR) ( 30, 50, 70 and 90 dB nHL) were measured for all participants (n = 37). Mild sensorineural hearing loss was found in 77.47% (n = 13) of the patients with GA-1, and normal hearing thresholds were seen in 23.53% (n = 4). There were three asymptomatic patients at the time of diagnosis [two developed mild mental motor retardation (MMR) and one developed severe MMR during the follow-up], one with a normal hearing threshold and two with mild hearing loss), and 14 symptomatic patients (three with normal hearing thresholds and 11 with mild hearing loss). Seven of the symptomatic patients diagnosed following an encephalopathic crisis required intensive care and showed significantly worse hearing thresholds than those without symptoms [20.86 ± 4.47 vs. 15.44 ± 3.96 decibel hearing level (dB HL), p = 0.039*], while five had mild-to-moderate hearing loss. Acute encephalopathic crisis had a negative effect on hearing function in the symptomatic patients. The emission and contralateral suppression amplitude values of the study group were significantly lower compared to the control group (p < 0.05). The I-V interpeak latency and absolute latencies of ABR waves I, III, and V of the study group were observed to be significantly prolonged and morphologically distorted compared to those of the control group (p < 0.05). Five patients had MMR, and three had moderate MMR; all eight had mild-to-moderate hearing loss. In addition, of the eight patients with mild MMR, four had mild hearing loss. In particular, the morphological findings of ABR waves were significantly worse in the patients with severe and moderate MMR (p < 0.05). There was a significant correlation between a macrocephaly history (12 patients) and hearing loss (p = 0.041*). Magnetic resonance imaging findings were evaluated in all the 17 patients with GA-1, and typical fronto-temporal atrophy and sylvian fissure enlargement were observed. Our findings support that GA-1 is associated with auditory impairment, primarily in symptomatic patients. Adequate audiological test battery evaluation is essential in this context, particularly for symptomatic patients with a history of encephalopathic crises.

Autism spectrum disorder in patients with inherited metabolic disorders-a large sample from a tertiary center.

BACKGROUND: There is increased awareness regarding the co-occurrence of autism spectrum disorder (ASD) and inherited metabolic disorders (IMD), and this is crucial for the management of both diagnoses in clinical practice. We aimed firstly to report twenty-two patients with a dual diagnosis of IMD and ASD who are still being followed up in the child metabolism outpatient clinic; secondly to evaluate the time of both IMD and ASD diagnosis and the clinical progress of their metabolic disorders to underline treatable conditions. METHODS: Among the patients admitted to the Pediatric Metabolism outpatient clinic because of IMD, twentytwo of them who had a diagnosis of ASD were included in the study. Data of the patients were collected from their medical records. The most recent progress of the patients concerning their metabolic disorder was obtained from the patients` files. RESULTS: Six cases with Phenylketonuria, 2 cases with partial Biotinidase Deficiency, 3 cases with Cerebral Creatine Deficiency Syndrome (CCDS), 5 cases with Mucopolysaccharidosis (MPS) Type-3b, 2 cases with MPS Type-3a, 1 case with MPS Type 4, 2 cases with Hypervalinemia and 1 case with Maple Syrup Urine Disease were all diagnosed as also having ASD. The diagnoses of CCDS and MPS Type 3 were after the diagnosis of ASD. Phenylketonuria and Mucopolysaccharidosis were the most common diagnoses in our study. In addition, rare entities such as MPS Type 3b and Type 4 and Hypervalinemia were also reported to co-occur with autism. CONCLUSIONS: Considering the co-occurrence of both disorders and implementing intervention strategies accordingly will certainly be beneficial in clinical practice and particularly in countries with a high rate of consanguinity.

Clinical and molecular characteristics of carnitineacylcarnitine translocase deficiency with c.270delC and a novel c.408C>A variant.

BACKGROUND: Carnitine-acylcarnitine translocase deficiency (CACTD) is a rare, autosomal recessive, and highly lethal fatty acid oxidation (FAO) disorder caused by defective acylcarnitine transport across the mitochondrial membrane. CACTD is characterized by severe episodes of hypoglycemia and hyperammonemia, seizures, cardiomyopathy, liver dysfunction, severe neurological damage, and muscle weakness. Herein, we described the clinical features, biochemical, and molecular findings of three patients with CACTD, presented with poor feeding, hypoglycemia, liver dysfunctions, and hyperammonemia, but died despite intensive treatment. CASES: All cases had similar signs and symptoms like poor feeding and respiratory failure associated with liver dysfunction. Urinary organic acid profiles in the presence of hypoglycemia and hyperammonemia led us to the possible diagnosis of one of fatty acid ß-oxidation defects. Results of the molecular analyses were compatible with CACTD. In addition to known mutation (c.270delC;p.Phe91Leufs*38) we detected a novel one (c.408C > A;p.Cys136*). CONCLUSIONS: All three cases died despite a very intensive therapy. Based on our experience with these three cases, it can be said that CACTD has a relatively poor prognosis, molecular studies are of most importance in suspected cases for the final diagnosis and such studies might be of help while giving genetic counselling and guidance to parents for future pregnancies.

A rare cause of hepatomegaly and dyslipidemia: lysosomal acid lipase deficiency.

BACKGROUND: Lysosomal acid lipase deficiency (LAL-D), also known as cholesteryl ester storage disease or Wolman disease, is a multi-systemic autosomal recessive genetic disorder caused by mutations in the lysosomal acid lipase gene (LIPA). CASE: A 14-year-old female patient was diagnosed as LAL-D with the findings of hepatomegaly, splenomegaly, elevated liver enzyme levels, and abnormal lipid profile. Her sister had similar laboratory and ultrasonographic findings. Both siblings had a homozygous c.894 G > A mutation in the LIPA gene, and their parents were heterozygous for this mutation. CONCLUSIONS: This case is one of the similar reports in the literature regarding clinical, biochemical, and genetic findings. It is well-known that LAL-D has overlapping clinical manifestations, and early diagnosis is quite challenging. Therefore, most patients die in the first year of life. After the determination of novel mutations in LAL-D patients, it is thought that LAL-D can present with heterogeneous signs and symptoms.

Glutaric aciduria type 1: Genetic and phenotypic spectrum in 53 patients.

INTRODUCTION: Glutaric aciduria type 1 (GA1) is a rare and inherited autosomal-recessive metabolic disorder that occurs in the deficiency of glutaryl-co-enzyme A dehydrogenase (GCDH) enzyme encoded by GCDH gene. In this study, we aim to retrospectively investigate the clinical, biochemical, and neuroradiological parameters and examine the spectrum of GCDH gene variants in Turkish patients with glutaric aciduria type 1. METHODS: This is a descriptive cross-sectional study. The study was conducted in fifty-three patients from 39 unrelated Turkish families who were diagnosed with GA1 based on their clinical presentation, neuroimaging, and biochemical measurements, at the department of pediatric metabolism of a university hospital between June 1998 and August 2019. Pathogenic variants screening of GCDH gene was performed by direct DNA sequence analysis in forty-six patients with GA1. Pathogenicity of the novel variants was predicted via computational programs. RESULTS: A total of 53 patients were diagnosed with GA1. Of those, 32 (60.3%) had encephalopathic crisis and 33 (62.3%) had macrocephaly. Twenty different pathogenic variants were detected, 7 of which are novel (p.Glu57Lys, p.Ser145Profs*79, p.Ser246Glyfs*96 p.Ala293Val, p.His348Gln, p.His417Tyr, p.Asp418Val). The p.Arg402Trp, p.Pro248Leu and p.Leu340Phe variants were the most common in Turkish patients, with a frequency of 21.2%, 18.2% and 12.1% respectively. CONCLUSION: This study is the first comprehensive research from Turkey that provides information about disease-causing variants in the GCDH gene. The identification of common variants and hot spot regions of the GCDH gene is important for genetic counselling and the prenatal diagnosis of Turkish patients with GA1.

Two cases of Vici syndrome presenting with corpus callosum agenesis, albinism, and severe developmental delay.

BACKGROUND: Vici syndrome is a rare autosomal recessive disease with phenotypically heterogeneous presentation. Characteristic features of the disease are oculocutaneous albinism, corpus callosum agenesis, cataract, cardiomyopathy, and immunodeficiency. CASE: Here we report two Turkish patients with Vici syndrome. One of these patients had a novel mutation in EPG5 and presented with idiopathic thrombocytopenic purpura (ITP) and maculopapular rashes similar to Stevens-Johnson syndrome, which has been previously reported in only a few cases in the literature. CONCLUSION: Vici syndrome presents with a typical phenotype which may facilitate diagnosis for infants with multisystemic disorders. ITP and maculopapular rashes might be added to the spectrum of findings of patients with Vici syndrome.

Caring for a Child with Phenylketonuria: Parental Experiences from a Eurasian Country.

OBJECTIVES: Phenylketonuria (PKU) and mild hyperphenylalaninemia (HPA) are characterized by increased blood phenylalanine concentrations varying from mild to severe. Management of PKU was reported to be time consuming and burdensome for caregivers. This study intended to explore the experiences of families caring for a child with PKU/HPA in a country with a high PKU rate. The aim of this study was to compare parental well-being between parents of children with and without dietary restrictions and to explore the factors associated with parental psychological well-being. METHODS: Participants were interviewed about their experiences, concerns, and challenges related to the disease by using a semistructured questionnaire. After the interview, parents filled out the Beck Depression Inventory and State-Trait Anxiety Inventory-Trait. RESULTS: This study highlighted the adverse psychological, financial, and social effects of the diagnosis and management of the disease regarding the lives of the families of children with PKU/HPA. Although parental anxiety scores of children with and without dietary restrictions were similar, depressive symptom scores were higher in parents of children with dietary restrictions. However, in multiple regression analysis, lower household income and absence of perceived social support were found to be independent factors associated with higher depressive symptom scores. Having a daughter diagnosed with PKU/HPA and lower household income were found to be factors associated with higher anxiety scores. CONCLUSION: This study revealed that income level, perceived social support, and gender of the child were factors associated with psychological well-being of parents caring for children with PKU/HPA. Health care professionals should identify the challenges faced by families and should be aware of risk factors associated with lower parental well-being to achieve better family adjustment and better health outcomes.

The effectiveness of enzyme replacement therapy on cardiac findings in patients with mucopolysaccharidosis.

Background This study aimed to determine cardiac findings in patients with mucopolysaccharidosis (MPS) and to assess the changes in these findings after enzyme replacement therapy (ERT). Methods A retrospective clinical cohort study was conducted on patients who were diagnosed with MPS between 1995 and 2018 in Hacettepe University, Division of Pediatric Metabolism. A total of 96 patients were diagnosed with MPS during the study period. Of these patients, 81 (84.3%) received ERT. Echocardiographic findings of the patients together with the 6-min walking test (6MWT) results before and after ERT were compared. Results Thirty-one participants (38.2%) were female, while 50 (61.8%) were male. The mean age of the participants was 11.97 ± 6.33 years (range: 1.8-30). Five patients (6.2%) had MPS type I, 14 (17.3%) had type II, 28 (34.6%) had type IVa, 33 (40.7%) had type VI and one (1.2%) had type VII. Before ERT, 69.4% of patients had mitral insufficiency (MI; mild: 40.5%, moderate: 16.5%, severe: 12.7%), 35.4% had aortic insufficiency (AI; mild: 22.8%, moderate: 12.7%) and 45.1% had tricuspid insufficiency (TI; mild: 39.2%, moderate: 2.5%). The median duration of the ERT was 3.5 years. The ERT significantly improved left ventricular hypertrophy (LVH), but all other study variables returned non-significant before and after treatment. ERT may improve LVH in MPS. Bearing in mind that MPS is a progressive disease, ERT seems to prevent significant deterioration of this ailment but is not able to reverse the already settled pathologies except for LVH. ERT is not able to reverse the damage, but provides stabilization; so it is best to initiate treatment before cardiac damage.

Do not Miss Rare and Treatable Cause of Early-Onset Hemolytic Uremic Syndrome: Cobalamin C Deficiency.

The most common disorder of vitamin B12 metabolism is methylmalonic aciduria and homocystinuria type cobalamin C (cblC), which accounts for most of the cases is referred to as cblC deficiency. Cobalamin deficiency is one of the causes of early-onset hemolytic uremic syndrome (HUS). Here, we present the cases of 2 infants with cobalamin deficiency who presented with early-onset HUS. The first patient was a 5-month-old female who was admitted to the hospital with seizure, pallor, and yellow-colored diarrheal stools. Initial laboratory examination showed direct Coombs test-negative hemolytic anemia. Later, she developed acute kidney injury and thrombocytopenia. Bone marrow aspiration showed megaloblastic features, and urinary examination showed elevated levels of methylmalonic acid (MMA), -methyl citrate, and 3-hydroxypropionic acid. Methionine-restricted diet, parenteral hydroxocobalamine, folinic acid, carnitine, and betaine were initiated. Hemolytic activity was -controlled with this treatment. Genetic screening showed homozygous mutation on the MMACHCgene (p.R161*[c.481C>T]). The second patient was a 3-month-old male infant who was admitted to the hospital with malaise and diarrhea. Laboratory examination showed direct Coombs test-negative hemolytic anemia with leukopenia. Later he developed acute kidney injury and thrombocytopenia. Bone marrow aspiration revealed megaloblastic changes. Urine organic acid test showed increased levels of MMA. Parenteral hydroxocobalamine, folinic acid, carnitine, and betaine were initiated. He died due to respiratory failure and cardiac arrest. Direct sequencing of MMACHC identified homozygous mutation, c.271dup A. CblC deficiency is an important cause of early-onset HUS and prompt diagnosis will provide specific treatment modalities.

Expanding the phenotype of phospholipid remodelling disease due to MBOAT7 gene defect.

MBOAT7 gene codes O-acyltransferase domain containing seven proteins which is one of four enzymes involved in remodeling of phosphoinositol phosphate (PIP) in LANDs cycle. We present clinical, neuroimaging, and genetic findings of 12 patients from 7 families with MBOAT7 gene defect, a recently defined novel phospholipid remodelling disease. To the best of our knowledge, our case series is the second report on patients with MBOAT7 gene defect. The patients present with global developmental delay particularly in speech and language skills, intellectual disability, stereotypical behavior, ataxic gait, early onset epilepsy with well response to medical treatment, strabismus and similar facial features. Common neuroimaging findings of the patients were folium dysgenesis of the cerebellum with a particular appearance, mild-to-moderate cerebellar atrophy, T2 hyperintensity of bilateral globus pallidius and dentate nuclei, enlarged perivascular areas, and mild thinning of the corpus callosum. Genome-wide genotyping and exome sequencing identified five different types of homozygous mutations in the MBOAT7 gene in all seven families which are p.Arg87*, p.Leu227ProfsX65, p.Gln376Lys, p.Trp426*, and chr19:54.666.173-54.677.766/11594 bp del. We conclude that clinical and neuroimaging findings of MBOAT7 gene defect may suggest the diagnosis and guide genetic tests.

Cognitive and behavioral impairment in mild hyperphenylalaninemia.

Evinç SG, Pektas E, Foto-Özdemir D, Yildiz Y, Karaboncuk Y, Bilginer-Gürbüz B, Dursun A, Tokatli A, Coskun T, Öktem F, Sivri HS. Cognitive and behavioral impairment in mild hyperphenylalaninemia. Turk J Pediatr 2018; 60: 617-624. As elevated phenylalanine (Phe) is detrimental to brain functions, determining a safe upper limit of blood Phe is important for initiation of treatment plans and setting Phe targets in hyperphenlalaninemic patients. It is accepted that Phe levels below 360 µmol/L does not impair brain function and hence does not require treatment. Therefore, we aimed to compare cognitive functions and attention-related problems among healthy children and untreated patients with hyperphenylalaninemia (HPA). This study included 41 hyperphenylalaninemic patients (`all HPA group`) aged 6-16 years with untreated blood Phe between 240 and 600 µmol/L and 29 healthy controls. `All HPA group` was further divided into 2 subgroups according to their lifetime median blood Phe levels as `Phe 360-600 µmol/L` and `Phe 240-360 µmol/L` groups. Wechsler Intelligence Scale for Children-IV (WISC-IV), Conners` Continuous Performance Test (CPT), Strength and Difficulties Questionnaire (SDQ) and Schedule for Affective Disorders and Schizophrenia for School-Age Children: Present and Lifetime Version (K-SADS-PL) were performed as a comprehensive neurocognitive, attention and behavioral assessment. The study illustrated that `all HPA` patients had significantly lower scores on all WISC-IV indexes compared to controls, except for Working Memory. Both `Phe 360-600 µmol/L` and `Phe 240-360 µmol/L` subgroups had lower Full Scale intelligence quotient (IQ) and Verbal Comprehension scores compared to controls. `All HPA` patients also had longer reaction times and more peer problems than controls, indicating attention deficits and behavioral problems. Since the results demonstrated that children with untreated Phe levels between 240-360 µmol/L are at higher risk for cognitive and attention-related problems, lowering the `safe` upper Phe level should be considered.

A Fanconi-Bickel syndrome patient with a novel mutation and accompanying situs inversus totalis.

Tastemel-Öztürk T, Bilginer-Gürbüz B, Teksam Ö, Sivri S. A Fanconi-Bickel syndrome patient with a novel mutation and accompanying situs inversus totalis. Turk J Pediatr 2017; 59: 693-695. Fanconi-Bickel syndrome is a rare autosomal recessive disorder of carbohydrate metabolism, caused by mutations in the SLC2A2 gene, that codes for the glucose transporter protein 2 (GLUT2). The disease is characterized by proximal renal tubular dysfunction, impaired glucose and galactose utilization, and accumulation of glycogen in the liver and kidney. Signs and symptoms of Fanconi-Bickel syndrome begin in infancy and include failure to thrive, hepatomegaly, hypophosphatemic rickets, and short stature. Here in we report a Turkish Fanconi-Bickel syndrome case who also has situs inversus totalis and a novel mutation that has not been described before.

Effects of methylphenidate on appetite and growth in children diagnosed with attention deficit and hyperactivity disorder.

The purpose of this study was to determine the levels of leptin, ghrelin, and nesfatin-1 to elucidate the causes of poor appetite and growth retardation in patients receiving methylphenidate therapy for attention deficit hyperactivity disorder. The study was performed on 89 male subjects; 48 patients and 41 healthy controls, aged 7-14 years. Following treatment, patients' leptin levels increased and ghrelin levels decreased while no significant change was found in nesfatin-1 levels. Of the 48 patients, 34 developed lack of appetite. In patients who developed lack of appetite, body weight SDS, body mass index (BMI), and BMI SDS were statistically significantly reduced; moreover, height SDS was reduced, though not to a statistically significant extent. This study attempted to elucidate the mechanisms that mediate the association between methylphenidate and appetite and growth, for which no studies have yet to be published.

An association of leishmaniasis and dyserythropoiesis in children.

Visceral leishmaniasis results in hematological problems such as cytopenias and coagulopathies. This disorder also has morphological effects on the bone marrow. Dyserythropoiesis is one of the most prominent seen with changes like multilobed nuclear cells and the appearance of bridges between nuclei and cytoplasms. Approximately half of the children with leishmaniasis showed dyserythropoietic findings in bone marrow aspirate slides. Because this in endemic regions, physicians of these countries must be alert to correctly diagnose disease and discriminate from other dyserythropoietic disorders.