Cigdem Aktuglu Zeybek

Inherited metabolic disorders in Turkish patients with autism spectrum disorders.

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 studys 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. Autism Res 2016, 9: 217–223.

Clinical and neuroradiological approach to fucosidosis in a child with atypical presentation

Fucosidosis is a rare lysosomal storage disease with clinical presentation of developmental retardation, coarse facial features, hepatosplenomegaly, dysostosis multiplex, and angiokeratomas. Here, a 7-year-old female patient with progressive dystonic movement disorder and loss of acquired motor skills is presented. Coarse facial feature and abnormal globuspallidus signaling in brain magnetic resonance imaging (MRI) led the patient to be investigated in terms of fucosidosis despite absence of hepatosplenomegaly, dysostosis multiplex, and angiokeratomas. Markedly decreased enzyme activity of alpha-fucosidosis led to the correct diagnosis. Conclusion: Various neurological findings have recently been reported in fucosidosis. However, neuroimaging findings have not been studied in detail except a few studies. It is critically important to discuss the wide neuroradiological spectrum of the disease and to highlight fucosidosis in differential diagnosis of bilateral pallidalhypointensity on T2-weighted images in brain MRI. In addition, description of atypical clinical findings of fucosidosis should avoid clinicians from diagnostic delay.

Screening Mucopolysaccharidosis Type IX in Patients with Juvenile Idiopathic Arthritis

Mucopolysaccharidosis is a group of lysosomal disorders of a deficiency of specific enzyme required for glycosaminoglycan degradation. Mucopolysaccharidosis type IX is the rarest form of mucopolysaccharidosis. To date, only four patients have been reported. The first reported patient had mild short stature and periarticular soft tissue masses; the other reported patients are clinically indistinguishable from juvenile idiopathic arthritis. In the present study, we screened mucopolysaccharidosis type IX among patients with juvenile idiopathic arthritis with hyaluronidase enzyme assay. One hundred and eight patients with JIA and 50 healthy age-matched control subjects were enrolled in the study. Among all patients, none had deficient hyaluronidase activity. Though serum Hyal-1 activity was significantly increased in JIA patients, compared with control subjects (p < 0.000), no correlation was found between CRP, ESR, and Hyal-1 activity (p = 0.187). In conclusion, the data reported in our study indicates that systemic metabolic investigation for hyaluronidase activity is not recommended in all patients with JIA.

Neonatal nonketotic hyperglycinemia: diffusion-weighted magnetic resonance imaging and diagnostic clues.

Nonketotic hyperglycinemia (NKH) is an autosomal recessive disorder, which is caused by a defect in the glycine cleavage system. Characteristic findings of this metabolic encephalopathy include generalized hypotonia, seizures, apneic attacks, lethargy, and coma. In this paper, we present the case of a 3-month-old male patient with NKH who presented with atypical clinical features in whom suggestive magnetic resonance imaging (MRI) findings lead to the correct diagnosis. A 3-month-old male patient was admitted to our pediatric nutrition and metabolism unit with complaint of generalized hypotonia. He was the first child of consanguineous parents and his prenatal, natal, and postnatal history was uneventful. He had no history of seizures. Feeding difficulty was noted. His physical examination revealed generalized hypotonia. He had spontaneous eye opening but during the examination, it was observed that he was not aware of his environment. He had no head control. Hematological and biochemical investigations including liver function and muscle specific enzymes, electrolyte levels, and renal functions were found normal. Acylcarnitine profile and urinary organic acid analysis were unremarkable. Plasma lactate and ammonia levels were in normal ranges. Brain diffusion-weighted MRI imaging revealed bilateral symmetrical diffusion restriction in the corona radiata, the posterior limb of the internal capsule and ventral brainstem corresponding to the course of the corticospinal tract, which was suggestive for the diagnosis of NKH (Fig. 1). Despite the absence of seizures, which is an important clinical finding in NKH, the disease was considered in the differential diagnosis based on MRI imaging and the existence of an altered level of consciousness. Plasma and cerebrospinal fluid (CSF) amino acid analyses were performed for definite diagnosis, and both plasma and CSF glycine levels were found remarkably elevated (890 and 131.3 lmol/L, respectively) with a typically high CSF-to-plasma glycine ratio (0,14). Definite diagnosis of NKH was based on characteristic biochemical findings. Although he had not an obvious sign of seizure, electroencephalography was performed and hypsarrhythmia pattern, which was compatible with the disease, was detected. Dextrometorphan and sodium benzoate therapies were started once the diagnosis was made. However, he became progressively lethargic and his condition continued to deteriorate. He died 2 months after the beginning of the treatment. Nonketotic hyperglycinemia is an autosomal recessive disorder, which is characterized by a rapid neurological & Tanyel Zubarioglu tanyel0554@yahoo.com

Phenotypic Expansion of Congenital Disorder of Glycosylation Due to SRD5A3 Null Mutation

We present a boy, admitted at 4 months, with facial dysmorphism, hypertrichosis, loose skin, bilateral inguinal hernia, severe hypotonia, psychomotor disability, seizures with hypsarrhythmia (West syndrome), hepatosplenomegaly, increased serum transaminases, iris coloboma, glaucoma, corneal clouding and bilateral dilated lateral ventricles, and extra-axial post-cerebellar space. Serum transferrin isoelectrofocusing (IEF) showed a type 1 pattern. Whole-exome genotyping showed a previously reported homozygous nonsense mutation c.320G>A; p.Trp107X in SRD5A3. Epilepsy and glaucoma have been reported only once in the 19 described SRD5A3-congenital glycosylation defect patients, and corneal clouding not at all.

Oculocutaneous tyrosinemia: A case report with delayed diagnosis and excellent response to dietary modification

303 Indian Journal of Dermatology, Venereology, and Leprology | May-June 2015 | Vol 81 | Issue 3 The important finding in this case was that subcorneal neutrophilic pustules and subcorneal eosinophilic pustules were observed simultaneously; however, it is difficult to explain the findings. We think that these two forms of pustules might be due to different pathogenic mechanisms or simply due to the time course of each lesion. A biopsy from the abdominal lesion performed 1 week after the appearance of the erythematous papules showed subcorneal eosinophilic pustules. By contrast, a biopsy from the right forearm performed 1 month after the occurrence of the vesicular eruptions displayed subcorneal neutrophilic pustules. Indeed, Takata et al.[1] performed a biopsy 3 weeks after onset and diagnosed eosinophilic cellulitis with subcorneal eosinophilic pustules, whereas Chao et al.,[2] performed a biopsy after 6 weeks and diagnosed eosinophilic cellulitis with subcorneal pustules containing both neutrophils and eosinophils. Eosinophils can release interleukin (IL)-8, which exhibits chemotactic activity for neutrophils.[5] We postulate that subcorneal eosinophilic pustules could be sequentially replaced by subcorneal neutrophilic pustules.

Biotinidase deficiency mimicking primary immune deficiencies.

Biotinidase deficiency (BD) is an inborn metabolic disorder inherited in an autosomal recessive manner. Partially due to high consanguinity rates in Turkey, BD incidence is high in Turkey. If left untreated, neurological abnormalities including seizures, hypotonia, sensorineural deafness, alopecia, egzamatous skin rash and candidiasis may occur. Three-years-old girl was admitted to hospital with recurrent infections, candidiasis and egzamatous skin rash. Immunological evaluation was normal. Associated deafness and consanguinity of the parents suggested BD which has been proven by enzyme activity measurement. With this report, we want to emphasise that BD can be the underlying cause of recurrent infections and candidiasis.

Lessons from two cases: is Fabry disease the correct diagnosis?

Fabry disease (FD) is an X linked inherited lysosomal storage disorder with complex multisystem involvement; it is caused by deficiency of the lysosomal enzyme α-galactosidase. Deficient enzyme activity leads to a wide spectrum of clinical manifestations consisting of dermatological, ophthalmological, cardiovascular, and urinary and central nervous system findings. As a result, FD should be considered in the differential diagnosis of many systemic diseases. Diagnosis of FD can arise from careful clinical and instrumental investigations, together with family history data and accurate interpretation of genetic and enzymatic analyses. Lack of knowledge on clinical findings of the disease and inept investigation methods unfortunately result in erroneous diagnosis. We present two patients who were referred to our clinic with a suspicion of ED and finally diagnosed as glycogen storage disorder type III and ornithine transcarbamylase deficiency, respectively.

Decreased serum biotinidase activity in adult patients with decompensated liver cirrhosis / Dekompanse karaciğer sirozlu erişkin hastalarda düşük serum biyotinidaz aktivitesi

Decreased serum biotinidase activity in adult patients with decompensated liver cirrhosis Objective: The liver is the major source of serum biotinidase. Therefore liver cirrhosis can lead to decreased serum biotinidase activity and biotin deficiency. The aim of this study was to assess serum biotinidase activity in adult patients with liver cirrhosis and to investigate the relationship between serum biotinidase activity and the degree of compensation of liver cirrhosis. Material and Method: A total 40 cirrhotic patients were included in the study (24 decompensated and 16 compensated) (mean age 53,5 yr, range 37-78 yr). 21 and 15 patients were associated with hepatitis B virus and hepatitis C virus, respectively, and 4 patients had cryptogenic cirrhosis. None of the patients exhibited clinical symptoms related to biotin deficiency. The control group consisted of 26 healthy persons (14 male and 12 female) (mean age 32 yr, range 20-50 yr). The statistical analyses were performed by student’s t test. Results: Serum biotinidase activities were found 5,7±1,6, 7,8±2 and 8,7±1,5 µmol/min/mL (mean±STD) (decompensated cirrhosis, compensated cirrhosis and the control group, respectively). Serum biotinidase activities in patients with decompensated cirrhosis were lower than both the patients with compensated cirrhosis and the control group’s activities (p=0,005, p 0,05). Conclusion: Our findings suggested that serum biotinidase activity was significantly lower in patients with decompensated cirrhosis. However, the patients with compensated cirrhosis had similar biotinidase activity in comparison with the control group. These results indicated that the decreased serum biotinidase activity was associated with severe impaired hepatocellular function although there were no clinical symptoms regarding the biotin deficiency. Whether these patients can benefit from biotin supplementation needs further investigations.