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BackgroundMucopolysaccharidosis VII (MPS VII) is an ultra-rare disease characterised by the deficiency of β-glucuronidase (GUS). Patients’ phenotypes vary from severe forms with hydrops fetalis, skeletal dysplasia and mental retardation to milder forms with fewer manifestations and mild skeletal abnormalities. Accurate assessments on the frequency and clinical characteristics of the disease have been scarce. The aim of this study was to collect such data.MethodsWe have conducted a survey of physicians to document the medical history of patients with MPS VII. The survey included anonymous information on patient demographics, family history, mode of diagnosis, age of onset, signs and symptoms, severity, management, clinical features and natural progression of the disease.ResultsWe collected information on 56 patients from 11 countries. Patients with MPS VII were classified based on their phenotype into three different groups: (1) neonatal non-immune hydrops fetalis (NIHF) (n=10), (2) Infantile or adolescent form with history of hydrops fetalis (n=13) and (3) Infantile or adolescent form without known hydrops fetalis (n=33). Thirteen patients with MPS VII who had the infantile form with history of hydrops fetalis and survived childhood, had a wide range of clinical manifestations from mild to severe. Five patients underwent bone marrow transplantation and one patient underwent enzyme replacement therapy with recombinant human GUS.ConclusionsMPS VII is a pan-ethnic inherited lysosomal storage disease with considerable phenotypical heterogeneity. Most patients have short stature, skeletal dysplasia, hepatosplenomegaly, hernias, cardiac involvement, pulmonary insufficiency and cognitive impairment. In these respects it resembles MPS I and MPS II. In MPS VII, however, one unique and distinguishing clinical feature is the unexpectedly high proportion of patients (41%) that had a history of NIHF. Presence of NIHF does not, by itself, predict the eventual severity of the clinical course, if the patient survives infancy.

Objective Mucopolysaccharidoses (MPS) represent a heterogeneous group of rare, inherited lysosomal storage disorders characterized by the accumulation of glycosaminoglycans in various tissues, including the orofacial region. This study aims to investigate the orofacial features and radiographic manifestations in a cohort of pediatric patients diagnosed with MPS. Materials and methods Thirty-five patients (18 males, 17 females) diagnosed with different subtypes of MPS underwent comprehensive oral and radiographic examinations. The presence and frequency of clinical and radiographic findings were documented. Radiographic analysis was feasible in 26 patients, with 9 excluded due to severe intellectual disability. The decayed, missing, and filled teeth (DMFT/dft); decayed, missing, and filled surfaces (DMFS/dfs) indices were recorded according to WHO criteria. The dental plaque scores were determined according to Silness & Löe plaque index. Data was analysed using SPSS 25.0, with descriptive statistics summarizing variables and Fisher’s Exact test applied for subgroup comparisons by MPS subtype; significance was set at p  < 0.05. Results The most frequent orofacial findings included tongue thrusting (80%, n  = 28/35), limited mouth opening (71%, n  = 25/35), macroglossia (71%, n  = 25/35), and anterior open bite (54%, n  = 19/35). Radiographic analysis revealed a thin mandibular cortex in 38% ( n  = 10/26) of cases, impacted teeth in 27% ( n  = 7/26), and a short mandibular ramus in 23% ( n  = 6/26). This is the first reported case of a talon cusp, a rare dental anomaly occurring in a patient with MPS-IV, highlighting a previously unrecognized association in the literature. The distribution of MPS types was: MPS-I ( n  = 3), MPS-II ( n  = 6), MPS-III ( n  = 8), MPS-IV ( n  = 10), MPS-VI ( n  = 7), and MPS-VII ( n  = 1). Conclusions Orofacial manifestations are frequently observed in patients with MPS and may serve as early indicators of the disorder, particularly within dental settings. Recognition of these features is essential, as they underscore the need for multidisciplinary care and routine dental evaluations to mitigate potential complications and enhance overall quality of life. Clinical relevance Orofacial abnormalities are common in children with MPS and may provide early clues to the diagnosis. This study emphasizes the importance of dental evaluations in identifying these signs, including the first reported case of a talon cusp in a patient with MPS. Early recognition by dental professionals can support timely diagnosis, guide appropriate referrals, and improve patient outcomes through coordinated, multidisciplinary care.

Background. Phenylketonuria (PKU), is an autosomal recessive disease leading to the conversion defect of phenylalanine (Phe) into tyrosine. Severe neurocognitive and behavioral outcomes are observed in untreated cases. The present paper aims to review clinical experiences and expert recommendations in diagnosis, treatment, and follow-up of pediatric PKU patients in Turkey. Methods. Two advisory board meetings were held in the year 2016 and 2017 with contributions of four leading experts in this field, and an online update meeting was held for final decisions about statements, and conclusions in January 2021. Considering management gaps in diagnosis, treatment, and follow-up of PKU, discussion points are defined. The Committee members then reviewed the Turkish and general literature and the final statements were formulated. Results. The diagnostic cut-off for dried blood spots should remain at 2 mg/dl. Treatment cut-off value is acceptable at 6 mg/dl. Compliance with an ideal follow-up list is strongly recommended. Total protein intake should not be limited. Age-related safe levels of protein intake should be encouraged with an additional 40% from L-amino acids supplements, a 20% compensatory factor to account for the digestibility and utilization of amino acids from the supplement, and a further 20% compensation to optimize Phe control. Cognitive impairment and intelligence quotient evaluations should be performed at least twice before 3 years of age. In pregnant women, the target Phe level should be < 5 mg/dl, and they should be followed-up weekly in the first trimester, then every 2 weeks after organogenesis. Novel pharmacological treatments are promising, but some of them have limitations for our country. Conclusions. Early diagnosis and treatment initiation; determination and standardization of diagnostic and treatment thresholds; treatment modalities and follow-up parameters are significant steps in treating PKU in the long term. PKU follow-up is a dynamic process with uncertainties and differences in clinical practice.

Introduction Gaucher disease (GD) is a lysosomal storage disorder causing systemic and skeletal complications. This study evaluates bone health in adult GD type 1 patients, focusing on skeletal complications, bone mineral density (BMD), and biochemical markers. Material and methods A cohort of adult GD type 1 patients followed up at Ege University Pediatric Metabolism Department were retrospectively examined. Results This study included 32 patients with GD type 1, comprising 11 males (34.4%) and 21 females (65.6%). The median age at diagnosis was 20.5 years (min: 3-max:65), and at enrolment, it was 35 years (min:18-max:71). Most patients (93.8%) had organomegaly, and 93.8% had cytopenia. Common genetic variants were p.Asn409Ser (60.9%), p.Leu483Pro (7.8%), and p.Asp448His(4.7%). All patients were on enzyme replacement therapy (ERT) for a median of 11 years (min:2-max:18). Bone complications included pathologic fractures in six patients (19%) and avascular necrosis in 12 patients (37.5%). Bone pain was reported by 93.7% of patients at admission and persisted in 59.4% during follow-up. DXA scans showed abnormal bone mineral density (BMD) in 62.5% of patients initially, with a significantly low bone density in 3.1% and reduced bone density in 59.3%. BMD improved with treatment, as evidenced by a significant increase in Z scores ( p <  0.05). Elevated chitotriosidase (75%), ferritin (50%), and immunoglobulin G (21.9%) levels were noted but did not correlate with BMD. Seven patients (22%) were splenectomized, all with bone issues. Discussion Bone health in GD involves multiple factors beyond biochemical markers. While ERT improves BMD, bone pain and fractures remain significant issues. Comprehensive management, including regular BMD monitoring and better vitamin D supplementation adherence, is crucial. Further research is needed to improve treatments for bone complications in GD.

Background/Objectives: Mucopolysaccharidosis type II (MPS II) is an inherited metabolic disorder characterized by progressive neurologic and extra-neurologic findings. We aimed to explore the age at symptom onset and at diagnosis as well as contribute to the phenotype–genotype association with new observations of MPS II based on a broad series of patients in Turkey. Methods: The presented study was retrospective and descriptive. Data on molecular analysis results, the age of onset and diagnosis, diagnostic delays, neurologic and extra-neurologic symptoms, enzyme and urine glycosaminoglycan (GAG) level results, brain magnetic resonance imaging, echocardiography, and electromyography were reviewed. Results: A total of 46 MPS II patients from 40 families were involved. The mean diagnosis age was 40.1 ± 46.8 months, and the diagnostic delay was 19.7 ± 40.4 months. While the mean age of diagnosis of the first cases in the families was 45 ± 24 months, the mean age of diagnosis of the second cases was 14 ± 15 months. The mean age at diagnosis was 42 ± 18 months in the patient group born before 2010, while it was 28 ± 22 months in the patient group born in 2010 and after. The last measurement of the height SDS value showed a significant difference (p = 0.004) between the groups that started ERT before the age of three and those who began ERT at the age of three and above. Five patients showed an attenuated phenotype without neurologic involvement. The sequencing of the IDS gene revealed 25 distinct variants, with 8 novel variants that have yet to be documented in the existing literature. Conclusions: The findings from the observations of this Turkish MPS II cohort emphasize that the actual prevalence of MPS II is probably underestimated and that it has a broad spectrum of clinical phenotypes, even without neurological impairment. In children, specific warning signs—including a coarse facial appearance, abdominal distension, speech delays, and macrocephaly—should raise suspicion and prevent delays in diagnosis. Conducting urine GAG and enzyme analyses is crucial for cases with clinical suspicion. Our data showed that the age of diagnosis tended to decrease over the years.

Background. Methylmalonyl CoA epimerase (MCE) deficiency was first reported in 2006 and only a few cases have been reported so far. The clinical spectrum of MCE deficiency ranges from asymptomatic to lifethreatening metabolic decompensation attacks. Case. Herein we report a patient diagnosed with MCE deficiency with recurrent acute metabolic ketoacidosis attacks and moderate MMA-uria that persisted in periods without decompensation. At presentation, organic acid profiles were dominated by increased 3 hydroxybutyrate. Conclusions. 3-Oxothiolase deficiency as a main ketolysis defects disorder was initially suspected. However, the subsequently repeated organic acid analyses demonstrated mild and persistent elevation of methylmalonic acid. This report provides a new phenotype of the clinical and biochemical characterization of MCE deficiency.

Familial hypercholesterolemia (FH) is an inherited metabolic disorder that increases cardiovascular risk from childhood. Despite its frequency, pediatric diagnosis and treatment remain limited, particularly in developing countries. Retrospective analysis of pediatric patients with genetically confirmed heterozygous FH (HeFH). Genetic testing included sequencing of the genes , , and . Clinical features, treatment responses, statin use, and adverse events were assessed and a comparative analysis was conducted between different statin types. Among the cohort of 124 patients only 28.2% of patients were diagnosed via routine lipid screening, though 90.3% had a positive family history. After diagnosis, 16.1% declined treatment and 41.1% were lost to follow-up. Most genetic diagnoses involved pathogenic variants; only a few cases involved APOB and PCSK9. Three novel variants were identified. Among treated patients, atorvastatin led to a greater median low density lipoprotein-cholesterol (LDL-C) reduction. A higher (though not statistically significant) proportion of pitavastatin users achieved LDL-C targets. LDL-C reduction was positively correlated with baseline LDL-C levels. For the majority of patients, statins were well tolerated; five patients had transient creatine kinase elevations that resolved with treatment interruption. This is the first large pediatric HeFH cohort study from Türkiye and provides data on both genetic background and treatment outcome. Despite genetic confirmation, significant gaps remain in early diagnosis, treatment acceptance, and long-term follow-up. Both atorvastatin and pitavastatin proved to be safe and effective. These results suggest a need for national screening programmes, family education, dietary counselling, and consistent follow-up.

Aromatic L-amino acid decarboxylase (AADC) deficiency is a disease in which neurological findings are dominant due to deficiencies in neurotransmitter synthesis. Hypoglycemia caused by autonomic dysfunction is one of the symptoms that may be encountered. Here we report a case of mild AADC deficiency presenting with hypoglycemia without any neurological signs. A 4-year-old girl presented with recurrent hypoglycemia. Her growth and development were normal. Plasma insulin and cortisol values were normal in the sample at the time of hypoglycemia. C8:1-Carnitine elevation was detected in the acylcarnitine profile. A clinical exome panel was performed with the suggestion of a fatty acid oxidation defect. However, a homozygous variant in the gene was detected. Furthermore, cerebrospinal fluid neurotransmitter analysis revealed low 5-hydroxyindolacetic acid and homovanillic acid and high 3-O-methyl-dopa and methyltetrahydrofolate (5 MTHF) consistent with AADC deficiency. Plasma AADC enzyme activity was low. The episodes of hypoglycemia were treated with uncooked cornstarch. This case suggests that AADC deficiency should be considered in some patients with hypoglycemia.

Objectives: To report ocular manifestations in patients with Fabry disease (FD) from a tertiary eye care center in Turkiye. Materials and Methods: This prospective, cross-sectional study included 30 eyes of 15 patients with FD. The diagnosis of FD was made based on a combination of clinical findings, genetic analysis, and biochemical evaluation. All participants underwent a detailed ophthalmic examination with special focus on the typical ocular features of FD (cornea verticillata, conjunctival aneurysms, cataract, retinal vessel tortuosity). Results: The mean age was 45[+ or -]17 years (range: 22-75 years), with a female/male ratio of 2:3. All patients had tortuous conjunctival vessels and 12 patients (80%) had conjunctival aneurysms. Cornea verticillata was present in 10 patients (66.6%), lens opacification in 4 patients (26.6%), and retinal vascular tortuosity in 8 patients (53.3%). All patients had at least two different ocular findings; most (3 heterozygotes/7 hemizygotes) had a combination of corneal verticillata and conjunctival vessel abnormality. The conjunctiva, cornea, and retina were affected together in 5 hemizygous patients (33.3%). One hemizygous patient had all FD-related ocular manifestations in both eyes. Conclusion: To our knowledge, this study is the first to describe the ocular manifestations of FD in the Turkish population. Although cornea verticillata is considered a hallmark of FD, it was absent in approximately one-third of patients. Moreover, cataract, another well-known feature of FD, was present in only 26.6% of the patients. Conjunctival vascular abnormality alone seems to be quite rare in FD, although it often accompanies other ocular manifestations. Therefore, recognition of other mild findings and special consideration of their associations may increase the diagnostic value of ocular findings in FD. Keywords: Cornea verticillata, conjunctival aneurysm, Fabry cataract, Fabry disease, metabolic diseases