RESUMEN
BACKGROUND: Old age, obesity, and certain chronic conditions are among the risk factors for severe COVID-19. More information is needed on whether inherited metabolic disorders (IMD) confer risk of more severe COVID-19. We aimed to establish COVID-19 severity and associated risk factors in patients with IMD currently followed at a single metabolic center. METHODS: Among all IMD patients followed at a single metabolic referral center who had at least one clinic visit since 2018, those with accessible medical records were reviewed for SARS-CoV-2 tests. COVID-19 severity was classified according to the WHO recommendations, and IMD as per the international classification of IMD. RESULTS: Among the 1841 patients with IMD, 248 (13.5%) had tested positive for COVID-19, 223 of whom gave consent for inclusion in the study (131 children and 92 adults). Phenylalanine hydroxylase (48.4%) and biotinidase (12.1%) deficiencies were the most common diagnoses, followed by mucopolysaccharidoses (7.2%). 38.1% had comorbidities, such as neurologic disabilities (22%) or obesity (9.4%). The majority of COVID-19 episodes were asymptomatic (16.1%) or mild (77.6%), but 6 patients (2.7%) each had moderate and severe COVID-19, and two (0.9%) had critical COVID-19, both of whom died. 3 patients had an acute metabolic decompensation during the infection. Two children developed multisystem inflammatory syndrome (MIS-C). Long COVID symptoms were present in 25.2%. Presence of comorbidities was significantly associated with more severe COVID-19 in adults with IMD (p < 0.01), but not in children (p = 0.45). Compared to other categories of IMD, complex molecule degradation disorders were significantly associated with more severe COVID-19 in children (p < 0.01); such a significant IMD category distinction was not found in adults. DISCUSSION: This is the largest study on COVID-19 in IMD patients relying on real-word data and objective definitions, and not on merely expert opinions or physician surveys. COVID-19 severity and long COVID incidence in IMD are probably similar to the general population, and the risk of acute metabolic decompensation is not likely to be greater than that in other acute infections. Disease category (complex molecule degradation) in children, and comorbidities in adults may be associated with COVID-19 severity in IMD. Additionally, the first documented accounts of COVID-19 in 27 different IMD are recorded. The high occurrence of MIS-C may be coincidental, but warrants further study.
Asunto(s)
COVID-19 , Enfermedades Metabólicas , Adulto , Niño , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Síndrome Post Agudo de COVID-19 , Factores de Riesgo , Gravedad del Paciente , Enfermedades Metabólicas/epidemiología , Obesidad/complicaciones , Obesidad/epidemiologíaRESUMEN
BACKGROUND: Phenylalanine (Phe)-restricted diet is associated with lower quality of life for patients with phenylketonuria (PKU), and a concern for caregivers of recently-diagnosed infants. Sapropterin is an oral drug used as an alternative or adjunct to dietary treatment. We have observed that some of the young infants initially managed successfully with sapropterin monotherapy have required dietary treatment in long-term follow-up. We aimed to determine the baseline factors associated with future initiation of dietary treatment in these patients. METHODS: Data were obtained retrospectively from the medical records of 80 PKU patients started on sapropterin monotherapy before 3 months of age between 2011 and 2021. RESULTS: The patients were followed for a median of 3.9 years (Q1-Q3: 2.5-5.75 years). Sapropterin was tapered down and discontinued in 5 patients (6.3%) as their Phe levels remained below 360 µmol/L without treatment. Sapropterin monotherapy was sufficient in 62 patients (77.5%), while 13 (16.2%) required dietary treatment. Phe and tyrosine (Tyr) levels, and Phe:Tyr ratios differed significantly among the patients maintained on sapropterin monotherapy and those started on dietary treatment, but the Phe:Tyr ratio at diagnosis was the most important independent baseline variable (OR: 1.61, 95% CI: 1.15-2.27, p = 0.006), with Phe:Tyr ratio at diagnosis >5.25 associated with dietary treatment (sensitivity: 90.0%, specificity: 81.8%). Genotypic phenotype value (GPV), unavailable at baseline, was also associated with dietary treatment (median GPV 9.2 vs. 3.8, p = 0.006), but some genotypes were not specific to the final treatment modality. DISCUSSION: We propose that the Phe:Tyr ratio at diagnosis is an important indicator to predict dietary requirement in young infants initially managed with sapropterin monotherapy.
Asunto(s)
Fenilalanina Hidroxilasa , Fenilcetonurias , Humanos , Lactante , Estudios Retrospectivos , Calidad de Vida , Fenilalanina , Fenilcetonurias/tratamiento farmacológico , Fenilcetonurias/genética , Dieta , Biopterinas , Fenilalanina Hidroxilasa/genéticaRESUMEN
Elevated serum prolactin concentrations occur in inherited disorders of biogenic amine metabolism because dopamine deficiency leads to insufficient inhibition of prolactin secretion. This work from the International Working Group on Neurotransmitter Related Disorders (iNTD) presents the results of the first standardized study on levodopa-refractory hyperprolactinemia (LRHP; >1000 mU/L) and pituitary magnetic resonance imaging (MRI) abnormalities in patients with inherited disorders of biogenic amine metabolism. Twenty-six individuals had LRHP or abnormal pituitary findings on MRI. Tetrahydrobiopterin deficiencies were the most common diagnoses (n = 22). The median age at diagnosis of LRHP was 16 years (range: 2.5-30, 1st-3rd quartiles: 12.25-17 years). Twelve individuals (nine females) had symptoms attributed to hyperprolactinemia: menstruation-related abnormalities (n = 7), pubertal delay or arrest (n = 5), galactorrhea (n = 3), and decreased sexual functions (n = 2). MRI of the pituitary gland was obtained in 21 individuals; six had heterogeneity/hyperplasia of the gland, five had adenoma, and 10 had normal findings. Eleven individuals were treated with the dopamine agonist cabergoline, ameliorating the hyperprolactinemia-related symptoms in all those assessed. Routine monitoring of these symptoms together with prolactin concentrations, especially after the first decade of life, should be taken into consideration during follow-up evaluations. The potential of slow-release levodopa formulations and low-dose dopamine agonists as part of first-line therapy in the prevention and treatment of hyperprolactinemia should be investigated further in animal studies and human trials. This work adds hyperprolactinemia-related findings to the current knowledge of the phenotypic spectrum of inherited disorders of biogenic amine metabolism.
RESUMEN
The aims of the study were to evaluate the prevalence of sleep-disordered breathing (SDB) by using polysomnography (PSG) in children with MPS IVA and MPS VI who underwent enzyme replacement therapy (ERT) and to analyze the effect on SDB of having upper airway surgery, pulmonary functions, and exercise capacity. A retrospective cross-sectional study was conducted on patients with MPS IVA (n:17) and MPS VI (n:11) aged under 19 years who underwent polysomnography. Descriptive and nonparametric analyses were performed for demographic, PSG, pulmonary function and exercise capacity variables. The frequency of sleep apnea in the study sample was 85.7% (24/28). Four patients (14.3%) had no sleep apnea, 15 (53.6%) had mild, and nine (32.1%) had moderate-to-severe sleep apnea. Two patients (7.1%) had central sleep apnea and 22 had obstructive sleep apnea (OSA) (78.6%). Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were negatively correlated to apnea-hypopnea index (AHI) (r = -0.594, p = .009; r = -0.636, p = .005, respectively). Despite ERT and previous upper airway surgery, the prevalence of OSA was high in patients with MPS IVA-MPS IV, emphasizing the importance of PSG screening for sleep disorders. Pulmonary function tests may be useful for predicting sleep apnea in patients with MPS IVA and MPS VI.
Asunto(s)
Mucopolisacaridosis IV/complicaciones , Mucopolisacaridosis IV/epidemiología , Síndromes de la Apnea del Sueño/epidemiología , Síndromes de la Apnea del Sueño/etiología , Adolescente , Factores de Edad , Biomarcadores , Análisis de los Gases de la Sangre , Niño , Preescolar , Estudios Transversales , Susceptibilidad a Enfermedades , Terapia de Reemplazo Enzimático , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Mucopolisacaridosis IV/diagnóstico , Mucopolisacaridosis IV/tratamiento farmacológico , Polisomnografía , Prevalencia , Pruebas de Función Respiratoria , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Síndromes de la Apnea del Sueño/diagnóstico , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/etiologíaRESUMEN
Strict control of hyperphenylalaninemia is necessary in pregnant women with phenylketonuria (PKU) in order to prevent phenylalanine embryopathy in the fetus, characterized by intrauterine growth restriction, dysmorphic facies, congenital heart disease, microcephaly and intellectual disability, collectively known as maternal PKU syndrome. Sapropterin dihydrochloride (SD), an alternative or adjunct to dietary therapy in patients with tetrahydrobiopterin (BH4)-responsive PKU, has recently been used in several cases to treat PKU during pregnancy with satisfactory results. Here, we report two pregnancies treated with SD and unrestricted diet in a patient with BH4-responsive mild PKU. The first pregnancy resulted in a partial hydatidiform mole and was terminated, whereas a healthy infant was born from the second pregnancy. Phenylalanine control was optimal in both pregnancies. To the best of our knowledge, this is the first report on the development of partial hydatidiform mole associated with SD treatment and the second report on molar pregnancy in PKU. While the relation between SD and molar pregnancy is unknown, further studies may be needed to investigate the possible effects of SD on fertilization.
Asunto(s)
Biopterinas/análogos & derivados , Mola Hidatiforme/etiología , Fenilcetonuria Materna/tratamiento farmacológico , Adulto , Biopterinas/uso terapéutico , Femenino , Humanos , Embarazo , Resultado del EmbarazoAsunto(s)
Antibacterianos/uso terapéutico , Vendajes de Compresión , Úlcera de la Pierna/etiología , Deficiencia de Prolidasa/complicaciones , Deficiencia de Prolidasa/tratamiento farmacológico , Prolina/uso terapéutico , Úlcera Cutánea/etiología , Administración Tópica , Adulto , Antibacterianos/administración & dosificación , Humanos , Masculino , Prolina/administración & dosificación , Resultado del Tratamiento , Adulto JovenRESUMEN
To assess stress levels and life hardships of patients with phenylketonuria and their parents. Between January 2020 and June 2020, 156 patients with PKU and their parents who arrived for regular examinations were included. Parents were asked to complete the parenting stress index, Zarit Burden Scale, and the Strengths and Difficulties Questionnaire (SDQ), and children over the age of 11 were asked to fill the Rosenberg Self-Esteem Scale, the State-Trait Anxiety Inventory, and the SDQ. We found a significant negative correlation between the Rosenberg Self-Esteem Scale and age at diagnosis (r = -0.27, Pâ =â .035), mother's age (r = -0.33, Pâ =â .009), and father's age (r = -0.38, Pâ =â .004). There was a significant positive correlation between the State-Trait Anxiety Inventory and patient's age (râ =â 0.36, Pâ =â .006), mother's age (râ =â 0.29, Pâ =â .031) and father's age (râ =â 0.38, Pâ =â .024). In the child form of the SDQ, emotional problems were significantly positively correlated with serum phenylalanine (Phe) levels at diagnosis (râ =â 0.35, Pâ =â .036), total points were significantly positively correlated with serum Phe levels at clinical examination (r = -0.34, Pâ =â .004), and social problems were significantly negatively correlated with the father's age (r = -0.34, Pâ =â .047). We found a significant positive correlation between the Zarit Burden Scale and number of siblings (râ =â 0.195, Pâ =â .023). In the parent form of the SDQ, emotional problems were significantly positively correlated with patient age (râ =â 0.217, Pâ =â .032), peer problems were significantly positively correlated with age at diagnosis (râ =â 0.211, Pâ =â .037), behavioral problems (râ =â 0.203, Pâ =â .045), and attention deficit and hyperactivity (râ =â 0.203, Pâ =â .045) were significantly positively correlated with serum Phe levels at diagnosis. Phenylketonuria is difficult to cope with both for the patients and their parents because of diet obligation, high expenditures for the formulas required for the diet, requirement of regular clinical examinations, and possible development of mental disability and psychiatric disorders. Patients and their families should be psychologically evaluated and support should be provided if needed.
Asunto(s)
Cuidadores , Fenilcetonurias , Estrés Psicológico , Humanos , Fenilcetonurias/psicología , Fenilcetonurias/sangre , Femenino , Masculino , Niño , Estrés Psicológico/psicología , Adulto , Cuidadores/psicología , Adolescente , Padres/psicología , Ansiedad/psicología , Preescolar , Fenilalanina/sangre , Encuestas y Cuestionarios , Autoimagen , Adulto Joven , Persona de Mediana EdadRESUMEN
BACKGROUND: Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism that, if untreated, causes Phe accumulation in the brain leading to neurophysiologic alterations and poor outcomes. Lifelong management centers on dietary Phe restriction, yet long-term complete metabolic control is unachievable for many adults. High blood Phe levels or chronic Phe and intact protein restriction in the diet may lead to somatic comorbidities. A systematic literature review was conducted to evaluate somatic comorbidities experienced by adults with PKU. METHODS: Clinical and observational studies reporting somatic comorbidities experienced by individuals with PKU aged ≥ 16 years (or classified as adults) evaluating a Phe-restricted diet with or without pharmacologic therapy versus no therapeutic intervention (including healthy controls), or pharmacologic therapy versus a Phe-restricted diet alone, were identified. PubMed® was searched (February 1, 2022 and updated November 1, 2023), using a pre-defined search strategy, followed by two-stage screening and data extraction. Included studies were grouped by PKU population comparison. RESULTS: 1185 records were screened; 51 studies across 12,602 individuals were extracted. Bone-related abnormalities were the most reported outcome (n = 21); several outcome measures were used. Original study groupings included: Phe-restricted diet versus healthy controls or reference values (n = 40); treatment-adherent versus those non-adherent (n = 12). Additional groups added as part of a protocol amendment included: different Phe-restricted diets (n = 4); severe versus less severe disease (n = 5). Vote counting indicated a higher burden of ≥ 1 comorbidity (or outcome measure) for the Phe-restricted diet group by 37 of 38 studies included in the analysis of Phe-restricted diet versus healthy controls; higher burden in healthy controls was reported in 12 studies. Vote counting was similar between those treatment adherent (n = 7) versus non-adherent (n = 10). CONCLUSIONS: Adults with PKU have a higher comorbidity burden than a non-PKU population. More robust studies are needed to better understand the relationship between effective metabolic control and comorbidity burden, using consistent outcome measures. This SLR was supported by BioMarin Pharmaceutical Inc., Novato, CA, and is registered with the Research Registry (reviewregistry1476).
Asunto(s)
Comorbilidad , Fenilcetonurias , Humanos , Fenilcetonurias/dietoterapia , Fenilcetonurias/epidemiología , Adulto , Fenilalanina/sangreRESUMEN
BACKGROUND: In 2011, a European phenylketonuria (PKU) survey reported that the blood phenylalanine (Phe) levels were well controlled in early life but deteriorated with age. Other studies have shown similar results across the globe. Different target blood Phe levels have been used throughout the years, and, in 2017, the European PKU guidelines defined new targets for blood Phe levels. This study aimed to evaluate blood Phe control in patients with PKU across Europe. METHODS: nine centres managing PKU in Europe and Turkey participated. Data were collected retrospectively from medical and dietetic records between 2012 and 2018 on blood Phe levels, PKU severity, and medications. RESULTS: A total of 1323 patients (age range:1-57, 51% male) participated. Patient numbers ranged from 59 to 320 in each centre. The most common phenotype was classical PKU (n = 625, 48%), followed by mild PKU (n = 357, 27%) and hyperphenylalaninemia (HPA) (n = 325, 25%). The mean percentage of blood Phe levels within the target range ranged from 65 ± 54% to 88 ± 49% for all centres. The percentage of Phe levels within the target range declined with increasing age (<2 years: 89%; 2-5 years: 84%; 6-12 years: 73%; 13-18 years: 85%; 19-30 years: 64%; 31-40 years: 59%; and ≥41 years: 40%). The mean blood Phe levels were significantly lower and the percentage within the target range was significantly higher (p < 0.001) in patients with HPA (290 ± 325 µmol/L; 96 ± 24%) and mild PKU (365 ± 224 µmol/L; 77 ± 36%) compared to classical PKU (458 ± 350 µmol/L, 54 ± 46%). There was no difference between males and females in the mean blood Phe levels (p = 0.939), but the percentage of Phe levels within the target range was higher in females among school-age children (6-12 years; 83% in females vs. 78% in males; p = 0.005), adolescents (13-18 years; 62% in females vs. 59% in males; p = 0.034) and adults (31-40 years; 65% in females vs. 41% in males; p < 0.001 and >41 years; 43% in females vs. 28% in males; p < 0.001). Patients treated with sapropterin (n = 222) had statistically significantly lower Phe levels compared to diet-only-treated patients (mean 391 ± 334 µmol/L; percentage within target 84 ± 39% vs. 406 ± 334 µmol/L; 73 ± 41%; p < 0.001), although a blood Phe mean difference of 15 µmol/L may not be clinically relevant. An increased frequency of blood Phe monitoring was associated with better metabolic control (p < 0.05). The mean blood Phe (% Phe levels within target) from blood Phe samples collected weekly was 271 ± 204 µmol/L, (81 ± 33%); for once every 2 weeks, it was 376 ± 262 µmol/L, (78 ± 42%); for once every 4 weeks, it was 426 ± 282 µmol/L, (71 ± 50%); and less than monthly samples, it was 534 ± 468 µmol/L, (70 ± 58%). CONCLUSIONS: Overall, blood Phe control deteriorated with age. A higher frequency of blood sampling was associated with better blood Phe control with less variability. The severity of PKU and the available treatments and resources may impact the blood Phe control achieved by each treatment centre.
Asunto(s)
Fenilalanina , Fenilcetonurias , Humanos , Fenilcetonurias/sangre , Fenilalanina/sangre , Masculino , Adolescente , Niño , Femenino , Preescolar , Europa (Continente) , Adulto , Adulto Joven , Estudios Retrospectivos , Lactante , Persona de Mediana Edad , Turquía/epidemiologíaRESUMEN
Classical galactosemia is an inherited recessive disorder of galactose metabolism caused by deficiency of the enzyme galactose-1-phosphate uridyl transferase (GALT), which is caused by mutations in the GALT gene. In this study, 56 Turkish patients diagnosed with galactosemia were screened for GALT gene mutations using Affymetrix resequencing microarrays. Eleven types of mutations were detected in these patients, including two novel mutations (R258G and G310fsX49) and nine recurrent mutations. We detected six patients who were homozygous for the E340* mutation and for N314D, L218L silent substitutions (Duarte-1 variant) in this study. The haplotype E340*, N314D and L218L has been reported only in Turkish patients, which suggests that the E340* mutation is specific for our population and might be spread by a Turk ancestor. In patients, the Duarte-1 allele was found with a frequency of 10.71%, whereas the Duarte-2 allele was not detected. Duarte-1 and Duarte-2 alleles were found to be present at a frequency of 2.3% and 1.4%, respectively, in the screening of 105 healthy individuals. Considering all detected mutations, it is a very important finding that exons 6 and 10 of the GALT gene account for 79% of all mutant alleles in the Turkish population. The most common mutation is Q188R, with a frequency of 55.35%.
Asunto(s)
Pueblo Asiatico/genética , Galactosemias/epidemiología , Galactosemias/genética , Variación Genética , UTP-Hexosa-1-Fosfato Uridililtransferasa/genética , Alelos , Exones , Frecuencia de los Genes , Silenciador del Gen , Homocigoto , Humanos , Mutación , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Análisis de Secuencia de ADN , TurquíaRESUMEN
The objective of this study was to examine the efficacy of a 5-week, tele-CO-OP intervention in children with organic acidemia. Thirty-four children were randomly divided into intervention and control groups. While 17 received the home program, 17 received the CO-OP Approach with telehealth twice a week along with the home program. Children were assessed through the Canadian Occupational Performance Measure, Pediatric Evaluation of Disability Inventory, Child and Adolescent Scale of Participation, Kid-KINDL Questionnaire, and Assistance to Participate Scale. Between-group analyses show significant benefits (p < .05) for the CO-OP group compared with the control group on the Performance and Satisfaction scales of the Canadian Occupational Performance Measure, and on the total scores of the Pediatric Evaluation of Disability Inventory, Child and Adolescent Scale of Participation, KINDL, and the Assistance to Participate Scale. The findings are preliminary results of benefits as this is the first trial, and the CO-OP approach applied through telerehabilitation had positive effects on children with organic acidemia.
Asunto(s)
Proyectos Piloto , Adolescente , Humanos , Niño , Canadá , Encuestas y CuestionariosRESUMEN
Early-onset long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency is a fatty acid ß-oxidation disorder with a poor prognosis. Triheptanoin, an anaplerotic oil with odd-chain fatty acids can improve the disease course. The female patient presented here was diagnosed at the age of 4 months, and treatment was started as fat restriction, frequent feeding, and standard medium-chain triglyceride supplementation. In follow-up, she had frequent rhabdomyolysis episodes (â¼8 per year). At the age of six, she had 13 episodes in 6 months, and triheptanoin was started as part of a compassionate use program. Following unrelated hospital stays due to multisystem inflammatory syndrome in children and a bloodstream infection, she had only 3 rhabdomyolysis episodes, and hospitalized days decreased from 73 to 11 during her first year with triheptanoin. Triheptanoin drastically decreased the frequency and severity of rhabdomyolysis, but progression of retinopathy was not altered.
Asunto(s)
Errores Innatos del Metabolismo Lipídico , Rabdomiólisis , Humanos , Niño , Femenino , Lactante , 3-Hidroxiacil-CoA Deshidrogenasas/metabolismo , Oxidación-Reducción , Triglicéridos/uso terapéutico , Errores Innatos del Metabolismo Lipídico/complicaciones , Errores Innatos del Metabolismo Lipídico/diagnóstico , Errores Innatos del Metabolismo Lipídico/tratamiento farmacológico , Rabdomiólisis/tratamiento farmacológico , Coenzima ARESUMEN
Many adults with phenylketonuria (PKU) rely on medical nutrition therapy (MNT; low phenylalanine (Phe) diet with protein substitutes/medical foods) to maintain blood Phe concentrations within recommended ranges and prevent PKU-associated comorbidities. Despite disease detection through newborn screening and introduction of MNT as early as birth, adherence to MNT often deteriorates from childhood onwards, complicating the assessment of its effectiveness in the long term. Via a modified Delphi process, consensus (≥70% agreement) was sought on 19 statements among an international, multidisciplinary 13-member expert panel. After three iterative voting rounds, the panel achieved consensus on 17 statements related to the limitations of the long-term effectiveness of MNT (7), the burden of long-term reliance on MNT (4), and its potential long-term detrimental health effects (6). According to the expert panel, the effectiveness of MNT is limited in the long term, is associated with a high treatment burden, and demonstrates that adults with PKU are often unable to achieve metabolic control through dietary management alone, creating an unmet need in the adult PKU population.
Asunto(s)
Terapia Nutricional , Fenilcetonurias , Recién Nacido , Adulto , Humanos , Niño , Consenso , Fenilcetonurias/terapia , Tamizaje NeonatalRESUMEN
Methylmalonic acidemia is an autosomal recessive metabolic disorder affecting the propionate oxidation pathway in the catabolism of several amino acids, odd-chain fatty acids, and cholesterol. Methylmalonic acidemia is characterized by elevated levels of methylmalonic acid in the blood and urine. Mutations in the MUT gene, encoding methylmalonyl-CoA mutase carries out isomerization of L-methylmalonyl-CoA to succinyl-CoA, cause methylmalonic acidemia. In this study, 30 Turkish patients diagnosed with mut methylmalonic acidemia were screened for mutations using custom designed sequencing microarrays. The study resulted in detection of 22 different mutations, 10 of which were novel: p.Q132*, p.A137G, c.753+1T, p.T387I, p.Q514E, p.P615L, p.D625V, c.1962_1963delTC, p.L674F, and c.2115_2116insA. The most common, p.P615T, was identified in 28.0% of patients. These results suggest that microarray based sequencing is a useful tool for the detection of mutations in MUT in patients with mut methylmalonic acidemia.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/genética , Análisis Mutacional de ADN/métodos , Predisposición Genética a la Enfermedad , Mutación/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Errores Innatos del Metabolismo de los Aminoácidos/enzimología , Secuencia de Aminoácidos , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Metilmalonil-CoA Mutasa/química , Metilmalonil-CoA Mutasa/genética , Datos de Secuencia Molecular , Polimorfismo Genético , Alineación de SecuenciaRESUMEN
Neurometabolic diseases diagnosed by cerebrospinal fluid (CSF) examination are GLUT1 deficiency, serine-deficiency syndromes, glycine encephalopathy, cerebral folate deficiency, neonatal vitamin-responsive epileptic encephalopathies, disorders of monoamine metabolism, and y-amino butyric acid (GABA) metabolism. We retrospectively analyzed and compared the demographic, clinical, laboratory, and neuroimaging features of 62 patients in whom CSF examination was performed. Of the 62 patients, 16 (25.8%) had a final diagnosis, including succinic semialdehyde dehydrogenase (SSADH) deficiency (n=4), aromatic amino acid decarboxylase (AADC) deficiency (n=4), L-dopa-responsive dystonia (n=3), glycine encephalopathy (n=2), pyridoxal-phosphate-dependent seizures (n=l), cerebral folate deficiency (n=1), and serine biosynthesi defect (n=1). Parental consanguinity was present in all patients except one Positive yield of a diagnostic lumbar puncture (LP) for the diagnosis of inherited neurotransmitter metabolism disorder was 25.8% overall. Oculogyric crisis (50%), diurnal variation (81.8%) and consanguinity (93.8%) were the only statistically significant variables between patients with and without a specific diagnosis. It is challenging to diagnose neurotransmitter defects, since there is no ideal set of clinical symptoms. In our cohort, consanguinity, diurnal variation and abnormal ocular movements were the most significant findings associated with a diagnosis of a specific neurometabolic disorder based on CSF examination. Early diagnosis is of great importance not only for specific treatment, but also for genetic counseling and prenatal diagnosis.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/líquido cefalorraquídeo , Punción Espinal , Adolescente , Distribución de Chi-Cuadrado , Niño , Preescolar , Ritmo Circadiano , Consanguinidad , Electroencefalografía , Femenino , Humanos , Lactante , Masculino , Neuroimagen , Estudios Retrospectivos , Estadísticas no ParamétricasRESUMEN
PURPOSE: To evaluate the effects of Fabry disease (FD) on the retinal microvasculature and choroidal vascular and structural characteristics. METHODS: This study included 10 patients with FD and 10 age-matched healthy controls. Binarized enhanced depth imaging optical coherence tomography (OCT) images were used to measure the total choroidal area, luminal area, and stromal area with ImageJ software. The choroidal vascularity index (CVI) was assessed. The vessel densities (VD) of the retinal capillary plexuses and foveal avascular zone (FAZ) area were measured with OCT-angiography. RESULTS: The most common anterior segment finding was cornea verticillata (60.0%) and the most frequent posterior segment finding was vascular tortuosity (50.0%). Intraretinal hyperreflective foci on B-scan OCT was observed in 50.0% of the cases. In Fabry cases, a linear mixed model with random intercept revealed that 1% change in CVI was related to -0.009 mm2 (p = .015) change in FAZ area and -0.047 mm change, (p = .024) in FAZ perimeter. In the presence of retinal vascular tortuosity, 1% change in CVI was related to -0.013 mm2 (p = .002) change in FAZ area and -0.052 mm change (p = .004) in FAZ perimeter. In the presence of hyperreflective foci, 1% change in CVI was related to -0.014 mm2 (p = .004) change in FAZ area and -0.064 mm change (p = .003) in FAZ perimeter. CONCLUSION: The significant negative associations between FAZ measurements and CVI suggest a possible interaction between the choroidal and retinal microvasculature of patients with FD. These alterations were more pronounced in the presence of hyperreflective foci and retinal vascular tortuosity.
Asunto(s)
Enfermedad de Fabry , Mácula Lútea , Coroides , Enfermedad de Fabry/complicaciones , Angiografía con Fluoresceína/métodos , Humanos , Vasos Retinianos , Tomografía de Coherencia Óptica/métodosRESUMEN
Gyrate atrophy is a rare metabolic disease characterized by hyperornithinemia, typical retinal and choroidal lesions, high myopia with marked astigmatism, early cataract formation, and autosomal recessive inheritance pattern. In this paper, we describe a 12-year-old boy presenting with high myopia and gyrate fundus lesions, in addition to 10-times elevated serum ornithine level.
Asunto(s)
Enfermedades de la Retina/diagnóstico , Niño , Angiografía con Fluoresceína , Atrofia Girata/diagnóstico , Atrofia Girata/patología , Atrofia Girata/terapia , Humanos , Masculino , Ornitina/sangre , Enfermedades de la Retina/sangre , Enfermedades de la Retina/patología , Enfermedades de la Retina/terapiaRESUMEN
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.
Asunto(s)
Ansiedad/psicología , Depresión/psicología , Padres/psicología , Fenilcetonurias/dietoterapia , Fenilcetonurias/enfermería , Apoyo Social , Factores Socioeconómicos , Adulto , Cuidadores/psicología , Niño , Femenino , Humanos , Masculino , Factores Sexuales , TurquíaRESUMEN
In maple syrup urine disease (MSUD), disease-causing mutations can affect the BCKDHA, BCKDHB or DBT genes encoding for the E1alpha, E1beta and E2 subunits of the multienzyme branched-chain alpha-keto acid dehydrogenase (BCKDH) complex. Here we summarize the MSUD genotypes of a cohort of 32 unrelated Turkish patients in whom both alleles at a single gene locus harbored presumable disease-causing nucleotide changes. The patients had different forms of MSUD, ranging from the severe classical form (26 patients) to severe and mild variants (6 patients). In all except two patients (92%), the mutations occurred homozygously. The mutational spectrum included 27 different sequence variations--12 changes in the BCKDHA, 10 in the BCKDHB, and 5 in the DBT genes. In 37% (12 patients) of a total of 64 alleles, the supposed disease-causing mutations were located in the BCKDHA gene, in 44% (14 patients) in the BCKDHB gene and in 19% (6 patients) in the DBT gene. The mutational profile is heterogeneous, although two mutations occurred three times and five mutations occurred twice. There was no cluster for a single mutation except for c.773G>A (p.Cys258Tyr) in the BCKDHA gene, a hypothetical founder mutation in the Camlidere population.