Clinical Features of 29 Patients with Hereditary Tyrosinemia I in Western Turkey

Aim:The aim of this study was to investigate the long-term outcome of hereditary tyrosinemia Type I (HTI) patients treated with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) to increase knowledge about the clinical outcome in these patients. We want to mention that the patients with HTI have heterogeneous clinic. Early diagnosis and early treatment important to prevent the complications.Materials and Methods:Aretrospective study was carried out with twenty nine patients with HTI and who had been followed up by Ege University Faculty of Medicine, Department of Pediatric Metabolic Diseases and Nutrition Unit between December 1996 and September 2017.Results:Eight patients were acute form, thirteen were subacute and eight patients were chronic form. Mean age onset of clinical symptoms was 3.7±1.6, 9±1.6 and 41±27 months in acute, subacute and chronic HTI patients, respectively. The mean interval from the first symptom the diagnosis was 12.2 months. Mean of follow-up was 82.2 months (minimum: 1 month-maximum: 203 months). Five patients of HTI diagnosed with hepatocellular carcinoma and neurogenic crises were detected in four patients.Conclusion:NTBC treatment is effective and improves the prognosis of HTI. But early diagnosis and treatment leads to much better outcome. Adherence to the diet and treatment and follow-up schedule of the patients are vital

Clinical, Biochemical and Molecular Characteristics of Fifteen Patients with Mucopolysaccharidosis Type II in Western Turkey

Aim:Mucopolysaccharidosis Type II (MPS II, Hunter syndrome, OMIM 309900) is a rare X-linked lysosomal storage disease due to a deficiency of the iduronate-2-sulfatase (IDS) enzyme, which is one of the degradative enzymes of mucopolysaccharides. The purpose of this study is to present the clinical, biochemical and molecular characteristics of fifteen patients with MPS II in western Turkey.Materials and Methods:A retrospective study was carried out on fifteen patients with MPS II who were followed up by Ege University Faculty of Medicine, Unit of Pediatric Metabolic Diseases and Nutrition between October 2004 and September 2017.Results:The age range of the patients enrolled in the study was between 11 months and 318 months at the time of diagnosis. The most common symptom was coarse face. On physical examination, all of the patients presented with coarse face, macrocephaly and organomegaly. Except for one patient, all other were severe phenotype. IDS activity was significantly decreased in all patients in whom enzyme analysis was performed. In this study, one novel mutation was described.Conclusion:This is the first study on the clinical and molecular characterization of Turkish MPS II patients. The majority of the patients had neurologic involvement with different degrees of severity. The molecular analysis revealed one novel mutation

Tyrosinemia Type I and Reversible Neurogenic Crisis After a One-Month Interruption of Nitisinone

Hereditary tyrosinemia Type I (HTI) is an autosomal recessive disorder due to a deficiency of the enzyme fumarylacetoacetate hydrolase. The liver is the primary organ that is affected and comorbidities with renal and neurologic systems and hepatocellular carcinoma can be seen as a long-term complication. An effective treatment has been available with 2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione (NTBC) since 1992. Neurogenic crises do not take place in HTI patients who are treated with NTBC. Here, we report on a seven-year-old boy who underwent a severe neurological crisis including anorexia, vomiting, weakness, hyponatremia, paresthesia and paralysis of the extremities, seizure and arterial hypertension after an interruption of NTBC treatment. With the re-introduction of NTBC, the patient gradually reacquired normal neurological functions, normal blood pressure and recovered completely

Clinical spectrum of early onset “Mediterranean” (homozygous p.P131L mutation) mitochondrial neurogastrointestinal encephalomyopathy

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive mitochondrial disorder characterized by cumulative and progressive gastrointestinal and neurological findings. This retrospective observational study, aimed to explore the time of presentation, diagnosis and clinical follow-up of 13 patients with a confirmed MNGIE disease of Mediterranean origin. The mean age of symptom onset was 7 years (6 months−21 years) and the average diagnosis age was 15.4 years ±8.4. Four of 13 patients (30%) died before 30 years at the mean age of 19.7 years ±6.8. Cachexia and gastrointestinal symptoms were observed in all patients (100%). The mean body mass index standard deviation score at diagnosis was 4.8 ± 2.8. At least three subocclusive episodes were presented in patients who died in last year of their life. The main neurological symptom found in most patients was peripheral neuropathy (92%). Ten patients (77%) had leukoencephalopathy and the remaining three patients without were under 10 years of age. The new homozygous “Mediterranean” TYMP mutation, p.P131L (c.392 C > T) was associated with an early presentation and poor prognosis in nine patients (69%) from five separates families. Based on the observations from this Mediterranean MNGIE cohort, we propose that the unexplained abdominal pain combined with cachexia is an indicator of MNGIE. High-platelet counts and nerve conduction studies may be supportive laboratory findings and the frequent subocclusive episodes could be a negative prognostic factor for mortality. Finally, the homozygous p.P131L (c.392 C > T) mutation could be associated with rapid progressive disease with poor prognosis

Clinical, Neuroimaging, and Genetic Features of the Patients with L-2-Hydroxyglutaric Aciduria

Aim:L-2-hydroxyglutaric aciduria (L2HGA) is a rare autosomal recessive encephalopathy caused by mutations in the L-2-hydroxyglutarate dehydrogenase gene.Materials and Methods:Here we discuss the clinical and molecular characteristics in patients with L2HGA.Results:There were eight patients with L2HGA. Their median age was 16 (9.5-37) years. Five of them were female and three of them were male. The main symptoms of the patients were psychomotor retardation (8/8), cerebellar ataxia (5/8), extrapyramidal symptoms (7/8) and seizures (4/8). All patients had behavioral problems. Elevated urinary L-2-hydroxy (L-2-OH) glutaric acid was detected and the median level of urine L-2-OH glutaric acid at diagnosis was 146 (60-1460 nmol/mol creat). Characteristic magnetic resonance imaging findings including subcortical cerebral white matter abnormalities with T2 hyperintensities of the dentate nucleus, globus pallidus and putamen were detected. Two patients had homozygous R335X, two patients had homozygous R282Q, two patients had homozygous R302L and one patient had compound heterozygous P302L/A64T mutation in L-2-hydroxyglutarate dehydrogenase (L2HGDH) gene.Conclusion:Because of the slow progression of the disease, the diagnosis of the patients is usually belated. L2HGA must be considered in the differential diagnosis based on clinical findings and specific findings in cranial magnetic resonance imaging. In our study, one of our patients has a novel mutation

Glutaric Aciduria Type I Diagnosis Case with Normal Glutaryl Carnitine and Urine Organic Acid Analysis

Glutaric aciduria Type I (GA-I) is a rare inherited metabolic disease, deficiency of glutaryl-CoA dehydrogenase results in accumulation of the putatively neurotoxic metabolites glutaric and 3-hydroxyglutaric acid (GA, 3-OH-GA) in body tissues, particularly within the brain. Here we presented a 3-year-old girl with hypotonia and dystonia diagnosed with GA-I although the repeated analysis of the carnitine profile and organic acid analyses were normal. The patient has motor, mental retardation, hypotonia. Her weight standard deviation score (SDS) was -1.86 SDS, height SDS was -0.55 SDS, head circumference SDS was -1.01. The physical examination was normal except severe hypotonia. Spot blood carnitine profile, blood amino acid, urine organic acid, lactic acid and pyruvic acid were normal in repeated analysis. Dystonia and spastic tetraparesis developed on her follow-up. Cranial magnetic resonance imaging revealed bilateral cortical atrophy and bilateral striatal and caudate nucleus T2 flair hyperintensities. In GCDH gene analysis p.Y123C (c.368A>G)/p.L340F (c.368A>G) mutation was found. There was no history of encephalopathy. The patient treated with levodopa and trihexyphenidyl and lysine-restricted diet. In the presence of bilateral striatal involvement and cortical atrophy and dystonia, GA-I should be kept in mind. Blood carnitine profile and urine organic acid analyses may not be consistent. It is important to evaluate the cases for genetic investigation

Clinical Experiments in Patients with Mucopolysaccharidosis Type VI (Maroteaux-Lamy Syndrome)

Amaç: Mukopolisakkaridoz (MPS) tip VI veya Maroteaux Lamy sendromu, arilsülfataz B eksikliği nedeni ile oluşan otozomal resesif kalıtılan bir lizozomal depo hastalığıdır. Klinik özellikler ve hastalığın şiddeti değişkendir. Ege Üniversitesi Tıp Fakültesi, Çocuk Sağlığı ve Hastalıkları Anabilim Dalı, Çocuk Beslenme ve Metabolizma Bilim Dalı tarafından izlenen MPS tip VI tanılı 11 hastanın tanı, klinik, laboratuvar ve izlem verileri kullanılarak hekimler arasında farkındalığın artırılması amaçlanmıştır.Gereç ve Yöntemler: Ege Üniversitesi Tıp Fakültesi, Çocuk Sağlığı ve Hastalıkları Anabilim Dalı, Çocuk Beslenme ve Metabolizma Bilim Dalı'nda 1996-2016 tarihleri arasında başvuran MPS tip VI tanılı 11 hastanın takibi yapıldı. Hastaların tanı, klinik, laboratuvar ve izlem verileri kullanıldı.Bulgular: On bir hasta (%55 erkek) çalışmaya alındı. Hastaların tanı yaşı ortalaması 5,38 yıl (minimum-maksimum: 1-11,58 yıl) idi. Başvuru yakınmaları değerlendirildiğinde dokuz (%82) hastada dismorfik yüz görünümü, üç (%27) hastada sık tekrarlayan üst solunum yolları enfeksiyonu, üç (%27) hastada kemik deformiteleri mevcuttu. Tüm hastalarda mitral kapak yetmezliği, yedi (%64) hastada aort kapak yetmezliği, üç (%27) hastada trikuspit yetmezliği ve bir (%9) hastada pulmoner hipertansiyon saptandı. Tedavi alamayan iki hastada ağır kardiak ve obstruktif tipte solunum problemleri mevcuttu. 2006 yılından itibaren değişik sürelerde enzim replasman tedavisi (galsülfaz, 1 mg/kg/hafta) yapıldı. Sonuç: Tedaviye erken başlanması, klinik sonuçlarda iyileşme sağlayarak, hastalığın ilerlemesini yavaşlattığı gösterilen galsülfaz varlığı nedeni ile MPS tip VI'nın erken tanısı önem taşımaktadır.Aim: Mucopolysaccharidosis (MPS) type VI or Maroteaux Lamy syndrome is an autosomal recessive lysosomal storage disorder resulting from a deficiency of arylsulfatase B. Clinical features and severity vary. We evaluated clinical, laboratory and follow-up findings of 11 patients diagnosed with MPS type VI between the years 1996-2016 by the Ege University Faculty of Medicine, Department of Pediatrics, Child Health and Disease, Division of Metabolism and Nutrition to raise awareness in clinicians.Materials and Methods: Eleven patients with MPS type VI between the years1996-2016 were evaluated by the Ege University Faculty of Medicine, Department of Pediatrics, Child Health and Disease Division of Metabolism and Nutrition. We analyzed the diagnostic, clinical, laboratory and follow-up findings of the patients.Results: Eleven patients (55% male) were evaluated. The mean age was 5.38 years at diagnosis. The most common presenting symptoms were progressive coarsening of the face (82%), reccurent upper respiratory tract disorders (27%) and bone deformities (27%). All patients had mitral regurgitation, 27% had aortic regurgitation, 9% had tricuspid regurgitation and only one patient had pulmonary hypertension. Two patients, who could not be treated, had severe cardiac and obstructive type pulmonary disorders. Enzyme replacement therapy (galsulfase) has been performed in various durations since 2006.Conclusion: Early diagnosis of MPS VI is imperative due to the availability of galsulfase shown to slow the progression of the disease with a more significant impact on clinical outcomes when the the treatment is initiated early