ABSTRACT
OBJECTIVE: Cerebrotendinous xanthomatosis (CTX) is an inherited metabolic disorder characterized by progressive neurologic and extraneurologic findings. The aim of this retrospective, descriptive study was to explore the time of presentation and diagnosis, and to expand the phenotype and genotype of CTX, based on a nationwide and comprehensive series of patients in Turkey. METHODS: The demographic, clinical, biochemical and genotypic characteristics of the CTX patients were reviewed. Data on molecular analysis, age of onset and diagnosis, diagnostic delay, neurologic and extraneurologic symptomatology, results of plasma cholestanol levels, brain magnetic resonance imaging and electromyography at the time of diagnosis were reviewed. RESULTS: 100 confirmed CTX patients from 72 families were included. The mean age at diagnosis was 28.16 ± 14.28 years, and diagnostic delay was 18.39 ± 13.71 years. 36 patients were diagnosed in childhood. Frequency of intention tremor (p = 0.069), peripheral neuropathy (p = 0.234) and psychiatric manifestations (p = 0.396) did not differ between two groups, demonstrating the high rate in pediatric patients. Three adult patients showed a milder phenotype without neurologic involvement. Seven patients had normal plasma cholestanol levels despite neurological impairment. Sequencing of the CYP27A1 gene revealed 25 different variants, with a novel c.671_672del variant not previously described in literature. CONCLUSION: Based on the observations of this Turkish CTX cohort, it is emphasized that the true prevalence of CTX is probably underestimated and that it has a wide spectrum of clinical phenotypes even without neurological impairment. In children, abnormal cerebellar findings, peripheral neuropathy and psychiatric findings associated with intellectual disability have been suggested as warning signs to avoid diagnostic delay. In cases of clinical suspicion, molecular analysis is recommended despite normal plasma cholestanol levels, as severe neurologic involvement may occur in CTX patients without elevated cholestanol levels.
Subject(s)
Cholestanetriol 26-Monooxygenase , Cholestanol , Xanthomatosis, Cerebrotendinous , Humans , Xanthomatosis, Cerebrotendinous/genetics , Xanthomatosis, Cerebrotendinous/blood , Xanthomatosis, Cerebrotendinous/diagnosis , Male , Female , Adult , Turkey/epidemiology , Adolescent , Child , Cholestanetriol 26-Monooxygenase/genetics , Young Adult , Middle Aged , Cholestanol/blood , Retrospective Studies , Child, Preschool , Magnetic Resonance Imaging , Phenotype , Brain/pathology , Brain/diagnostic imaging , Brain/metabolism , Mutation , Genotype , Age of OnsetABSTRACT
The wide range of clinical symptoms observed in patients with Fabry disease (FD) often leads to delays in diagnosis and initiation of treatment. Delayed initiation of therapy may result in end-organ damage, such as chronic renal failure, hypertrophic cardiomyopathy, and stroke. Although some tools are available to identify undiagnosed patients, new comprehensive screening methods are needed. In this study, the outcomes of the cascade screening applied to three index cases with FD from 2 familes were investigated. In the pedigree analysis, 280 individuals were included; out of them, 131 individuals underwent genetic testing and cascade screening for FD. During the screening program, a total of 45 individuals were diagnosed, with a diagnostic ratio of 1:15. The average age at diagnosis for all individuals was 30.9 ± 17.7 years, and %25 were pediatric cases (mean age 9.5 ± 5.9 years). Thirty affected relatives were diagnosed from the two index cases in Family 1 and 15 individuals were diagnosed from one index case in Family 2. There were 13 consanguineous marriages observed among 2 pedigres, in two both spouses were affected, leading to two homozygous affected daughters in one couple. In regions where there is a high prevalence of consanguineous marriages, implementing the cascade screening approach to identify all individuals at risk can be beneficial for patients with FD, specifically women and children.
Subject(s)
Fabry Disease , Genetic Testing , Pedigree , Humans , Fabry Disease/genetics , Fabry Disease/diagnosis , Fabry Disease/epidemiology , Female , Male , Adult , Genetic Testing/methods , Child , Adolescent , Middle Aged , Young Adult , Consanguinity , alpha-Galactosidase/genetics , Child, PreschoolABSTRACT
Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive genetic disorder affecting the biosynthesis of dopamine, a precursor of both norepinephrine and epinephrine, and serotonin. Diagnosis is based on the analysis of CSF or plasma metabolites, AADC activity in plasma and genetic testing for variants in the DDC gene. The exact prevalence of AADC deficiency, the number of patients, and the variant and genotype prevalence are not known. Here, we present the DDC variant (n = 143) and genotype (n = 151) prevalence of 348 patients with AADC deficiency, 121 of whom were previously not reported. In addition, we report 26 new DDC variants, classify them according to the ACMG/AMP/ACGS recommendations for pathogenicity and score them based on the predicted structural effect. The splice variant c.714+4A>T, with a founder effect in Taiwan and China, was the most common variant (allele frequency = 32.4%), and c.[714+4A>T];[714+4A>T] was the most common genotype (genotype frequency = 21.3%). Approximately 90% of genotypes had variants classified as pathogenic or likely pathogenic, while 7% had one VUS allele and 3% had two VUS alleles. Only one benign variant was reported. Homozygous and compound heterozygous genotypes were interpreted in terms of AADC protein and categorized as: i) devoid of full-length AADC, ii) bearing one type of AADC homodimeric variant or iii) producing an AADC protein population composed of two homodimeric and one heterodimeric variant. Based on structural features, a score was attributed for all homodimers, and a tentative prediction was advanced for the heterodimer. Almost all AADC protein variants were pathogenic or likely pathogenic.
Subject(s)
Amino Acid Metabolism, Inborn Errors , Aromatic-L-Amino-Acid Decarboxylases , Humans , Prevalence , Dopamine/metabolism , Genotype , Amino Acid Metabolism, Inborn Errors/epidemiology , Amino Acid Metabolism, Inborn Errors/genetics , Amino Acids/geneticsABSTRACT
OBJECTIVES: TANGO2 deficiency is a rare inborn error of metabolism, with distinct clinical features. The clinical presentations of TANGO2 deficiency are developmental delay, speech difficulties, intellectual disability, non-life-threatening paroxysmal neurologic episodes (TANGO2 spells), acute metabolic crises, cardiac crises, seizures and hypothyroidism. Patients may die in acute metabolic crises. Here we report our experience in the management of an acute metabolic crisis in TANGO2 deficiency. CASE PRESENTATION: A 9-year-old patient diagnosed with TANGO2 deficiency was admitted with fever, fatigue, unable to walk. In follow up, encephalopathy, rhabdomyolysis and arrhythmia were detected. Vitamin B-complex was started. Our patient's mental status and rhabdomyolysis improved dramatically, and cardiac crises ended without Torsades de pointes, ventricular tachycardia and/or fibrillation or myocardial dysfunction. CONCLUSIONS: With this report, we aimed to show the effectiveness of vitamin B-complex in the management of acute metabolic crises.
Subject(s)
Brain Diseases , Rhabdomyolysis , Humans , Child , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/diagnosis , Seizures/etiology , VitaminsABSTRACT
X-linked ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle defect. The disease severity ranges from asymptomatic carrier state to severe neonatal presentation with hyperammonaemic encephalopathy. We audited the diagnosis and management of OTCD, using an online 12-question-survey that was sent to 75 metabolic centres in Turkey, France and the UK. Thirty-nine centres responded and 495 patients were reported in total. A total of 208 French patients were reported, including 71 (34%) males, 86 (41%) symptomatic and 51 (25%) asymptomatic females. Eighty-five Turkish patients included 32 (38%) males, 39 (46%) symptomatic and 14 (16%) asymptomatic females. Out of the 202 UK patients, 66 (33%) were male, 83 (41%) asymptomatic and 53 (26%) symptomatic females. A total of 19%, 12% and 7% of the patients presented with a neonatal-onset phenotype in France, Turkey and the UK, respectively. Vomiting, altered mental status and encephalopathy were the most common initial symptoms in all three countries. While 69% in France and 79% in Turkey were receiving protein restriction, 42% were on a protein-restricted diet in the UK. A total of 76%, 47% and 33% of patients were treated with ammonia scavengers in Turkey, France and the UK, respectively. The findings of our audit emphasize the differences and similarities in manifestations and management practices in three countries.
ABSTRACT
Background: Glycogen storage diseases type IIIa and b (GSDIII) are rare inherited metabolic disorders that are caused by deficiencies of the glycogen debranching enzyme, resulting in the accumulation of abnormal glycogen ('limit dextrin') in the muscles. The cardiac storage of limit dextrin causes a form of cardiomyopathy similar to primary hypertrophic cardiomyopathy. Treatment with a high fat diet is controversial but we report a positive outcome in a child with cardiomyopathy. Case presentation: A 9-year-old boy with GSDIIIa developed left ventricular hypertrophy at 4.3 years of age. A high-fat (50%), high protein (20%), low-carbohydrates (30%) diet was introduced. After 18 months, echocardiogram, biochemical and clinical parameters improved (Creatine Kinase (CK), 1628â1125 U/L; left ventricular outflow tract (LVOT), 35â20 mmHg; interventricular septum (IVS), 21â10 mm). The diet was abandoned for 2 years resulting in reversal of symptoms, but recommencement showed improvement after 6 months. Conclusion: A high fat, high protein and low carbohydrate diet was successful in reversing cardiomyopathy. This form of treatment should be considered in children with GSD IIIa with cardiomyopathy.
ABSTRACT
OBJECTIVE: We aimed to present the characteristics, genetic analysis results, long-term progno- sis of our patients with distal kidney tubular acidosis, and the relationship between hyperam- monemia and distal kidney tubular acidosis. MATERIALS AND METHODS: Biochemical, clinical, and imaging findings were collected at presen- tation and the last clinic visit, and results of the genetic analysis were recorded. RESULTS: Our study included 9 patients (3 female, 33%). The median age at diagnosis was 3 months, and the median follow-up period was 111 months. Height standard deviation scores were less than -2 in 4 (44%) patients at presentation and in 3 (33%) at the last clinic visit. The median estimated glomerular filtration rate was 98 mL/min/1.73 m2 at presentation and 126 mL/min/1.73 m2 at the last clinic visit. We have found 8 different types of mutations of 2 genes, including 6 in the ATP6V0A4 gene, 2 in the SLCA4A1 gene, and 2 of them were novel. At the time of presentation, nephrocalcinosis and hypercalciuria were present in all our patients, but at the last visit, only 1 patient had hypercalciuria. Sensorineural hearing loss was found in 4 of our patients with a mutation in the ATP6V0A4 gene. Serum ammonia levels were found to be high in 3 patients with mutations in the ATP6V0A4 gene. CONCLUSION: Adequate metabolic control is essential for optimal growth and preserved kidney function in distal kidney tubular acidosis patients. Distal kidney tubular acidosis may be associ- ated with hyperammonemia. We recommend keeping potassium levels at high-normal levels to reduce ammonia levels, especially in the absence of acidosis.
Subject(s)
Hyperferritinemia , Lymphohistiocytosis, Hemophagocytic , Female , Humans , Male , Proteinuria/diagnosis , Proteinuria/etiologySubject(s)
Lupus Erythematosus, Systemic , Proteinuria , Female , Humans , Male , Proteinuria/diagnosis , Proteinuria/etiologyABSTRACT
Alkaptonuria (AKU) is an inborn error of metabolism caused by the deficiency of homogentisate 1,2-dioxygenase (HGD) as a result of a defect in the HGD gene. HGD enzyme deficiency results in accumulation of homogentisic acid (HGA) in the body, which in turn leads to multisystemic clinical symptoms. The present study aimed to investigate the presenting symptoms, age at diagnosis, and clinical and genetic characteristics of AKU patients followed-up in different centers in Turkey. In this cross-sectional, multicenter, descriptive study, medical records of 66 AKU patients were retrospectively evaluated. Patients' data regarding demographic, clinical and genetic characteristics were recorded. HGD database (http://hgddatabase.cvtisr.sk/) was used to identify HGD gene variants. Of the patients, 37 (56.1%) presented with isolated dark urine and 29 (43.9%) were diagnosed based on the clinical symptoms or family screening. One of these patients was on follow-up for 2 years due to Parkinsonism and was diagnosed with AKU on further analyses. Signs of ochronosis such as joint pain, low back pain and renal stones developed in childhood in 7 patients. Eight patients were diagnosed with depression via psychiatric evaluation. There were 14 (21.2%) patients operated on for ochronosis. The most frequent mutation observed in the patients was c.175delA, which was followed by c.674G > A and c.1007-2A > T mutations. Four novel mutations (c.189G > A, c.549+1G > T, c.1188+1G > A, and c.334 T > G) were identified in the patients included in the study. In addition to the known signs such as dark urine and skin pigmentation, symptoms involving different systems such as neurological findings and depression can also be encountered in AKU patients. The presence of a change in urine color needs to be questioned in patients presenting with different symptoms such as arthralgia/arthritis, renal stones or low-back pain, particularly in childhood, when skin ochronosis is not pronounced, and further examination should be performed.
Subject(s)
Alkaptonuria/genetics , Homogentisate 1,2-Dioxygenase/genetics , Phenotype , Adolescent , Adult , Alkaptonuria/diagnosis , Alkaptonuria/epidemiology , Child , Child, Preschool , Depression/epidemiology , Diagnosis, Differential , Early Diagnosis , Female , Humans , Infant , Kidney Calculi/epidemiology , Male , Middle Aged , Mutation , Ochronosis/epidemiology , TurkeyABSTRACT
Cerebrotendinous xanthomatosis (CTX) is a lipid storage disease caused by deficiency of sterol 27-hydroxylase enzyme encoded by CYP27A1 gene. This multicenter, cross-sectional descriptive study aimed to document clinical characteristics of CTX patients of different ages, clinical presentations of early-diagnosed patients, and responses to short-term chenodeoxycholic acid (CDCA) treatment. Seven of 11 CTX patients were diagnosed in childhood. Three patients (27%) had neonatal cholestasis, seven (63%) patients had a history of frequent watery defecation started in infantile period, and eight (72.7%) patients had juvenile cataract. Four patients in the adult age group had pyramidal signs and parkinsonism symptoms. The mean Mignarri score at diagnosis was significantly lower in the pediatric patients (267.8 ± 51.4) than in the adult patients (450.0 ± 64.0, p = 0.001). No significant difference was determined between pediatric patients and adult patients regarding plasma cholestanol concentration at diagnosis (p = 0.482). The frequency of defecation decreased with treatment in six children, who had diarrhea at admission. Compared to pretreatment values, patients' body weight and standardized body mass index significantly increased at the 12th month of treatment. In conclusion, Mignarri scores are lower in the pediatric patients than in adult patients since the most determinative signs of the CTX disease are not apparent yet in the childhood. The disease is frequently overlooked in routine practice as the disease presents itself with different clinical combinations both in adults and in children. CTX is potentially a treatable disease; thereby, enhanced awareness is critically important for early diagnosis particularly in children.
Subject(s)
Chenodeoxycholic Acid/pharmacology , Cholestanol/blood , Early Diagnosis , Xanthomatosis, Cerebrotendinous/complications , Xanthomatosis, Cerebrotendinous/physiopathology , Adolescent , Adult , Child , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Xanthomatosis, Cerebrotendinous/diagnosisABSTRACT
BACKGROUND: Ochronotic arthropathy (OcA) refers to excessive homogentisic acid (HGA) deposition in the musculoskeletal system. Our current understanding of OcA is limited, as there are less than a thousand alkaptonuria (AKU) cases reported in the literature. Herein, we investigated the rheumatological manifestations of OcA in a group of adult AKU patients. METHODS: Adult AKU patients with symptoms suggestive of OcA were included. Patients underwent a detailed rheumatological assessment. Laboratory testing, including autoantibodies and radiological investigations such as conventional X-rays, and magnetic resonance imaging (MRI) were performed. RESULTS: Eight out of 12 (66%) patients had symptoms consistent with OcA. The median age at OcA symptoms was 36 (27-48) years, and the presenting symptom was back pain in 87.5% of the patients. All patients had chronic back pain, and three (37.5%) had an inflammatory type of pain character. Radiographic sacroiliitis based on X-rays was present in 2 (25%) cases. MRI of the sacroiliac joints documented bone marrow edema in five (62.5%), and spinal MRI identified corner inflammatory lesions in three patients (37.5%). One patient (12.5%) had rheumatoid arthritis. Extra-articular involvement, including enthesitis (n = 1; 12.5%), interstitial lung disease (n = 1; 12.5%), and scleritis (n = 1; 12.5%), was also noted. CONCLUSION: The frequent occurrence of OcA-related inflammatory manifestations in our patients contradicts the conventional concept of OcA as a non-inflammatory disorder. The activation of inflammatory pathways, possibly by the HGA products, may responsible for this condition.Significance and innovationsAbout three-fourths of adult ochronotic arthropathy (OcA) patients in our group had associated inflammatory disease.OcA associated inflammatory diseases were showing a severe phenotypeNearly half of the OcA patients required early prosthesis operations compared to their healthy counterparts.
Subject(s)
Ochronosis , Osteoarthritis , Alkaptonuria/complications , Alkaptonuria/diagnostic imaging , Cartilage, Articular , Humans , Ochronosis/complications , Ochronosis/diagnostic imaging , SpineABSTRACT
Renal-hepatic-pancreatic dysplasia-1 (RHPD1) is an ultra-rare genetic disorder with a high mortality. It is caused by biallelic pathogenic variants in NPHP3 , which encode nephrocytin, an important component of the ciliary protein complex. The NPHP3 -related disease phenotype is diverse with RHPD1, nephronophthisis-3, and Meckel syndrome-7. In this case report, we present a female infant with hepatomegaly, cholestasis, and elevated transaminases who was found to carry a homozygous c.2975C > T variant of NPHP3. This is the first description of this genotype and RHPD1 phenotype in the literature. The patient is currently being closely monitored for the necessity of combined renal and liver transplantation under supportive treatment.
ABSTRACT
Maple syrup urine disease (MSUD), also known as branched-chain α ketoaciduria, is a metabolic disorder caused by an inborn deficiency in the activity of the branched-chain α-ketoacid dehydrogenase complex. Severe neurological damage occurs in most patients with MSUD although the exact mechanism of neurotoxicity still remains unknown. Studies have suggested that neuropathology in patients with MSUD may be related to oxidative stress. L - carnitine mediates the transport of fatty acids into the mitochondria that are required for ß-oxidation and ATP production. Along with the important roles it plays in lipid metabolism, L-carnitine also protects tissues from oxidative damage through its antioxidant properties. The study included a total of 15 patients with MSUD who attended regular follow-up visits, and 15 age-matched healthy control subjects, and aimed to investigate L - carnitine levels in treated patients with MSUD and healthy control subjects. L - carnitine levels were found to be significantly lower in the patient group than in the healthy controls. No significant correlation was identified between the plasma branched-chain amino acids leucine, isoleucine, valine, and L - carnitine levels. Patients with MSUD can be treated with adjuvant therapy with L - carnitine supplementation.
ABSTRACT
Urea cycle disorders (UCDs) are rare inherited metabolic conditions that impair the effectiveness of the urea cycle responsible for removing excess ammonia from the body. The estimated incidence of UCDs is 1:35 000 births, or approximately 113 new patients with UCD per year. This review summarizes neuropsychological outcomes among patients with the eight UCDs in reports published since 1980. Rates of intellectual disabilities published before (and including) 2000 and after 2000 were pooled and compared for each UCD. Since diagnoses for UCDs tended to occur earlier and better treatments became more readily available after the turn of the century, this assessment will characterize the extent that current management strategies have improved neuropsychological outcomes. The pooled sample included data on cognitive abilities of 1649 individuals reported in 58 citations. A total of 556 patients (34%) functioned in the range of intellectual disabilities. The decline in the proportion of intellectual disabilities in six disorders, ranged from 7% to 41%. Results from various studies differed and the cohorts varied with respect to age at symptom onset, age at diagnosis and treatment initiation, current age, severity of the metabolic deficiency, management strategies, and ethnic origins. The proportion of cases with intellectual disabilities ranged from 9% to 65% after 2000 in the seven UCDs associated with cognitive deficits. Positive outcomes from some studies suggest that it is possible to prevent or reverse the adverse impact of UCDs on neuropsychological functioning. It is time to "raise the bar" in terms of expectations for treatment effectiveness.
Subject(s)
Cognition/physiology , Intellectual Disability/epidemiology , Intellectual Disability/etiology , Urea Cycle Disorders, Inborn/complications , Urea Cycle Disorders, Inborn/epidemiology , Adolescent , Adult , Age of Onset , Child , Child, Preschool , Europe/epidemiology , Female , Humans , Infant , Infant, Newborn , Intellectual Disability/diagnosis , Intellectual Disability/therapy , Male , Middle Aged , Neuropsychological Tests , Treatment Outcome , United States/epidemiology , Urea Cycle Disorders, Inborn/psychology , Urea Cycle Disorders, Inborn/therapy , Young AdultABSTRACT
Classical galactosemia is an autosomal recessive inborn error of metabolism caused by biallelic pathogenic variants in the GALT gene. With the benefit of early diagnosis by newborn screening, the acute presentation of galactosemia can be prevented. In this study, we describe the clinical phenotypes, time of diagnosis and GALT genotypes of 76 galactosemia patients from Turkey, where the disease is not yet included in the newborn screening program. The median age at first symptom was 10 days (range 5-20), while the median age at diagnosis was 30 days (range 17-53). Nearly half of the patients (36 patients, 47.4%) were diagnosed later than age 1 month. Fifty-eight individuals were found to have 18 different pathogenic variants in their 116 mutant alleles. In our sample, Q188R variant has the highest frequency with 53%, the other half of the allele frequency of the patients showed 17 different genotypes. Despite presenting with typical clinical manifestations, classical galactosemia patients are diagnosed late in Turkey. Due to the geographical location of our country, different pathogenic GALT variants may be seen in Turkish patients. In the present study, a clear genotype-phenotype correlation could not be established in patients.
Subject(s)
Biomarkers/analysis , Galactosemias/genetics , Mutation , Neonatal Screening/methods , UTP-Hexose-1-Phosphate Uridylyltransferase/genetics , Child , Child, Preschool , Female , Follow-Up Studies , Galactosemias/diagnosis , Gene Frequency , Genotype , Humans , Infant , Infant, Newborn , Male , Phenotype , Prognosis , Time FactorsABSTRACT
Background Oxidative stress may be one of the causes responsible for mental retardation in phenylketonuria (PKU) patients. Phenylalanine (Phe) reduces antioxidant defense and promotes oxidative stress by causing increase in reactive oxygen-nitrogen species. Our study aimed to investigate the effect of different treatments (amino acid mixture/large neutral amino acid [LNAA] supplements) on oxidative stress which are applied to late-diagnosed patients. To the best of our knowledge, this is the first study to investigate the effect of LNAA supplements on oxidative stress. Methods Twenty late-diagnosed classic PKU patients were included in this study. Patients were classified into two groups: patients under Phe-restricted diet and using Phe-free amino acid mixtures (Group I) (mean age: 13.8 ± 2.8), and patients taking LNAA supplements (Group II) (mean age: 14.8 ± 3.8). Healthy controls (mean age: 13.6 ± 4.8) with ages consistent with the ages of the patients in the experimental groups were included. Results Glutathione peroxidase is lower in patients of taking LNAA supplements than the control group (p = 0.022). Coenzyme Q10 is lower in patients of using Phe-free amino acid mixtures than the control group and it is significantly higher in Group II than Group I (p = 0.0001, p = 0.028, respectively). No significant differences were detected in total antioxidant status, total oxidant status, oxidative stress index, paraoxonase 1 and L-carnitine levels. Conclusions Different treatments affect oxidative stress parameters in PKU patients. In this study, although patients were followed up with classic PKU, patient-specific adjuvant antioxidant therapies should be implemented in response to oxidative stress.
Subject(s)
Amino Acids, Neutral/administration & dosage , Antioxidants/administration & dosage , Oxidative Stress/drug effects , Phenylketonurias/metabolism , Adolescent , Child , Dietary Supplements , Female , Humans , Male , Reactive Oxygen Species/metabolism , Treatment Outcome , Young AdultSubject(s)
Brain Diseases, Metabolic, Inborn/diagnosis , Leukoencephalopathies/diagnosis , Purpura/diagnosis , Brain Diseases, Metabolic, Inborn/diagnostic imaging , Brain Diseases, Metabolic, Inborn/genetics , Child , Female , Humans , Leukoencephalopathies/diagnostic imaging , Leukoencephalopathies/genetics , Magnetic Resonance Imaging , Purpura/diagnostic imaging , Purpura/geneticsABSTRACT
Mental retardation, which occurs in phenylketonuric patients, is associated with increased levels of phenylalanine, increased oxidative stress, and an imbalance of amino acids in the brain. Recent studies have shown that oxidative stress plays a role in the pathogenesis of phenylketonuria. In this work, we aimed to compare the influence of blood phenylalanine levels on oxidative stress parameters in phenylketonuric patients who divided patients into groups according to blood Phe levels during follow-up visits and compared these groups with healthy controls. Results showed significant differences in glutathione peroxidase (GSHPx), coenzyme Q10 (Q10), Q10/cholesterol, and L-carnitine levels in phenylketonuria patients and the control group. GSHPx, Q10, and Q10/cholesterol levels were significantly lower in poor adherence patients than in the control groups. L-carnitine levels were significantly increased in good adherence patients than poor adherence patients and decreased in poor adherence patients than healthy controls. No correlations were observed between phenylalanine and L-carnitine concentrations in poor adherence group. No significant differences were observed in paraoxonase 1 (PON1), total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) levels. As a result, in this work, poor adherence patients are prone to oxidative stress. Although the patients may have the same diagnosis, patients have different clinical characteristics and different prognosis. Antioxidants can be used as an adjuvant therapy in order to avoid neurological damage in these patients.