Background
Most patients with organic acidemia suffer from recurrent infections. Although neutropenia has been reported in multiple studies, other components of the immune system have not been ...evaluated thoroughly. This study was conducted to assess the immune status of patients with organic acidemia (OA).
Methods
Thirty‐three patients with OA who were followed up in Istanbul University‐Cerrahpasa, Cerrahpasa School of Medicine, Nutrition and Metabolism Department and a total of 32 age‐ and sex‐matched healthy controls were enrolled to the study. The demographic and clinical data were recorded retrospectively from patient files. Complete blood counts, immunoglobulins, and lymphocyte immunophenotyping were recorded prospectively in a symptom‐ (infection‐) free period.
Results
Of the 33 patients enrolled to the study, 21 (88%) were diagnosed with methylmalonic acidemia, 10 (33%) with propionic acidemia, and two (6.6%) with isovaleric acidemia. The mean age of the patients with OA and healthy subjects were 5.89 ± 4.11 years and 5.34 ± 4.36, respectively (P = 0.602). Twenty‐nine (88%) of the patients had experienced frequent hospital admission, 13 (39%) were admitted to pediatric intensive care unit, and 18 (55%) suffered from sepsis. Naïve helper T cells and recent thymic emigrants were significantly lower in OAs (P < 0.001). Various defects in humoral immunity have also been documented including memory B cells and immunoglobulins.
Conclusions
Patients with OAs may show adaptive immune defects rendering them susceptible to infections. Metabolic reprogramming based on nutritional modifications may be a promising therapeutic option in the future.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Infectious diseases can result in a catabolic state and possibly trigger an acute metabolic decompensation in inborn errors of metabolism (IEM), which could be life threatening. Studies ...regarding the course of severe acute respiratory syndrome coronavirus 2 infections in patients with IEM are generally limited to case reports. Here, we aimed to evaluate the clinical findings of coronavirus disease 2019 (COVID‐19) and describe the impact of severe acute respiratory syndrome coronavirus 2 infections on metabolic outcomes in IEM patients.
Methods
Patients who were diagnosed with different types of IEM and developed microbiologically confirmed COVID‐19 infection were included. Clinical findings and laboratory results were recorded retrospectively in terms of both IEM and COVID‐19.
Results
Eleven patients with diagnosis of intoxication type metabolic disorders, five patients with energy metabolism disorders, and six patients with complex molecular disorders were enrolled. The most frequent clinical finding was fever (52.1%) followed by fatigue/myalgia (47.8%). None of the patients was younger than 1 year. None of the patients presented severe or critical disease. In terms of metabolic decompensation, two patients diagnosed with propionic acidemia, one patient with methylmalonic acidemia and one patient with 3‐hydroxy‐3‐methylglutaryl‐CoA lyase deficiency presented clinical and biochemical findings of an acute metabolic attack.
Conclusions
Based on our results, IEM are not found to be an additional risk factor for severe COVID‐19 infection. However, patients with intoxication type and energy metabolism disorders should be considered as a vulnerable population for COVID‐19 and have a major risk of developing acute metabolic decompensation that can lead to life‐threatening complications.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The main treatment for pyridoxine-nonresponsive cystathionine-β-synthase deficiency is a strict diet. Most centers prescribe low-protein diets based on gram-protein exchanges, and all protein sources ...are weighed. The purpose of this study is to investigate the effects of a more liberal methionine (Met)-based diet with relaxed consumption of fruits and vegetables on metabolic outcomes and dietary adherence. Ten patients previously on a low-protein diet based on a gram-protein exchange list were enrolled. The natural protein exchange lists were switched to a "Met portion exchange list". Foods containing less than 0.005 g methionine per 100 g of the food were accepted as exchange-free foods. The switch to Met portioning had no adverse effects on the control of plasma homocysteine levels in terms of metabolic outcomes. It resulted in a significant reduction in patients' daily betaine dose. All patients preferred to continue with this modality. In conclusion, methionine-portion-based medical nutrition therapy with relaxed consumption of fruits and vegetables seems to be a good and safe option to achieve good metabolic outcomes and high treatment adherence.
Phenylketonuria is an inherited metabolic disorder that leads to neurobehavioral dysfunction. The main treatment is a low-phenylalanine diet and/or the cofactor tetrahydrobiopterin. Regular ...outpatient follow-up care and measurement of the phenylalanine levels in the blood are required. We aimed to analyze the economic burden of phenylketonuria on families and the state. The patients with phenylketonuria were divided into three groups according to their treatment: a low-phenylalanine diet group (
= 50), a tetrahydrobiopterin group (
= 44), and a group taking tetrahydrobiopterin together with the diet (
= 25). A comparative cost analysis was carried out. The annual economic burden to the state was calculated to average EUR 18,801 ± 15,345 and was lowest in the diet group, then in the tetrahydrobiopterin group, and highest in the tetrahydrobiopterin + diet group (
< 0.001). Out-of-pocket costs amounted to EUR 1531 ± 1173 per year, and indirect losses averaged EUR 2125 ± 1930 per year for all families. The economic loss was significantly lower in the families taking tetrahydrobiopterin than in the other groups (
= 0.001). The combined use of medical nutrition and BH4 treatments has been shown to increase the economic burden on the state. Reimbursing low-protein products and increasing the number of patients eligible for financial allowances may reduce the economic burden on families.
Cerebrotendinous xanthomatosis (CTX) is a rare, chronic, progressive, neurodegenerative disorder requiring life-long care. Patients with CTX often experience a diagnostic delay. Although early ...diagnosis and treatment initiation can improve symptoms and prognosis, a standardised approach to diagnosis, treatment and management of patients is not yet established. To assess expert opinion on best care practices for patients with CTX using a modified Delphi method. A multidisciplinary group of healthcare professionals with expertise in CTX responded to a 3-round online questionnaire (n = 10 in Rounds 1 and 2; n = 9 in Round 3), containing questions relating to the diagnosis, treatment, monitoring, multidisciplinary care and prognosis of patients with CTX. Determination of consensus achievement was based on a pre-defined statistical threshold of greater than or equai to 70% Delphi panellists selecting 1-2 (disagreement) or 5-6 (agreement) for 6-point Likert scale questions, or greater than or equai to 70% Delphi panellists choosing the same option for ranking and proportion questions. Of the Round 1 (n = 22), Round 2 (n = 32) and Round 3 (n = 26) questions for which consensus was assessed, 59.1%, 21.9% and 3.8% reached consensus, respectively. Consensus agreement that genetic analyses and/or determination of serum cholestanol levels should be used to diagnose CTX, and dried bloodspot testing should facilitate detection in newborns, was reached. Age at diagnosis and early treatment initiation (at birth, where possible) were considered to have the biggest impact on treatment outcomes. All panellists agreed that chenodeoxycholic acid (CDCA) is a lifetime replacement therapy which, if initiated early, can considerably improve prognosis as it may be capable of reversing the pathophysiological process in CTX. No consensus was reached on the value of cholic acid therapy alone. Monitoring patients through testing plasma cholestanol levels and neurologic examination was recommended, although further research regarding monitoring treatment and progression of the disease is required. Neurologists and paediatricians/metabolic specialists were highlighted as key clinicians that should be included in the multidisciplinary team involved in patients' care. The results of this study provide a basis for standardisation of care and highlight key areas where further research is needed to inform best practices for the diagnosis, treatment and management of patients with CTX.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objective
In this study, we performed analysis of brainstem reflexes and movement disorders using surface polymyogram in L-2-hydroxyglutaric aciduria (L2HGA). We also reviewed all cases in the ...literature with detailed clinical and radiological description to analyze the anatomical correlates of involuntary movements.
Patients and method
We performed surface electromyography of appropriate muscles, long-loop reflexes, and somatosensory evoked potentials and analyzed the neuroimaging findings in patients with L2HGA and recorded blink reflex (BR), auditory startle response (ASR), and startle response after somatosensory stimuli (SSS) in patients and healthy subjects. We also performed a systematic literature search to identify the association of neuroimaging findings and movements disorders in previous patients with L2HGA.
Results
Thirteen patients were enrolled in the study. Among them, ten had low-amplitude postural tremor with a frequency between 4 and 7 Hz. The tremor was predominant on distal parts of the upper extremities. Postural tremor was accompanied by negative myoclonus in one-third. The BR, ASR, and SSS, all, were hypoactive. There was a close association of postural tremor with cerebellar atrophy in patients who participated in this study and by the analysis of the previously reported patients.
Conclusions
Low-amplitude postural tremor is common in L2HGA. It is related with cerebellar atrophy. Although the neuroimaging shows no overt lesions at the brainstem, there is a functional inhibition at this level.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aim
There are no recommended guidelines or clinical studies on safety of COVID‐19 vaccines in patients with inborn errors of metabolism (IEMs). Here, we aimed to examine the relationship between ...COVID‐19 vaccination and metabolic outcome in paediatric IEM patients.
Methods
Patients with IEM between the ages of 12 and 18 were enrolled. Term metabolic decompensation was defined as acute disruption in metabolic homeostasis due to vaccination. Clinical and biochemical markers were compared between pre‐ and post‐vaccination periods.
Results
Data from a total of 36 vaccination episodes in 18 patients were included. Thirteen patients had intoxication‐type metabolic disorders including organic acidemia (OA), urea cycle disorders (UCDs), maple syrup urine disease (MSUD) and phenylketonuria (PKU); 4 patients had energy metabolism disorders including fatty acid metabolism disorders and LIPIN 1 deficiency; and 1 patient had glycogen storage disorder (GSD) type 5. Seventeen patients received BNT162b2, and 1 received CoronaVac because of an underlying long QT syndrome. Fatty acid metabolism disorders, LIPIN 1 deficiency and GSD type 5 were included in the same group named ‘metabolic myopathies’. In two PKU patients, plasma phenylalanine level increased significantly within 24 h following the second dose of vaccination. None of the OA, UCD, MSUD and metabolic myopathy patients experienced acute metabolic attack and had emergency department admission due to metabolic decompensation within 1 month after vaccination.
Conclusions
COVID‐19 vaccines did not cause acute metabolic decompensation in a cohort of 18 children with IEM.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Aim
Tuberculin skin test (TST) is still used in diagnostic algorithms of childhood tuberculosis (TB). QuantiFERON TB Gold In‐Tube assay (QFT‐GIT) is an alternative test to TST based on the detection ...of interferon‐gamma release upon in vitro induction of peripheral mononuclear cells by TB antigens. In this study, we aimed to determine the diagnostic value and performance of QFT‐GIT for active childhood TB.
Methods
This retrospective study was conducted between January 2005 and December 2011 in three referral hospitals in Turkey with 124 children who were diagnosed with definite active TB. Sensitivity values of TST and QFT‐GIT were determined by accepting the microbiological confirmation as the gold standard of diagnosis of TB.
Results
In our study, sensitivity of QFT‐GIT and TST was found to be 65 and 66% respectively. However, combined usage of QFT‐GIT and TST was found to be more sensitive (85%) than TST or QFT‐GIT alone (P < 0.0001). Although negative results of QFT‐GIT or TST did not exclude the diagnosis of active TB in children, their positivity supported the diagnosis. Specificity could not be measured as only microbiologically confirmed cases of Mycobacterium tuberculosis disease were enrolled in the study.
Conclusion
Although sensitivities of TST and QFT‐GIT are too low to exclude active TB, their positivity supports diagnosis of active TB in children concomitant with signs and symptoms. QFT‐GIT and TST should be used together to enhance diagnostic sensitivity and could help exclude a diagnosis of TB if the pretest probability is low.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
SARS-CoV-2 infection can lead to a life-threatening acute metabolic decompensation in children with inborn errors of metabolism (IEM), so vaccination is mandatory. However, IEMs can also impair ...innate or adaptive immunity, and the impact of these immune system alterations on immunogenicity and vaccine efficacy is still unknown. Here, we investigated humoral immune responses to the BNT162b2 mRNA COVID-19 vaccine and clinical outcomes in pediatric IEM patients.
Fifteen patients between 12-18 years of age with a confirmed diagnosis of IEM, and received BNT162b2 were enrolled to the study. Patients with an anti-SARS-CoV-2 IgG concentration >50 AU/mL before vaccination were defined as "COVID-19 recovered" whereas patients with undetectable anti-SARS-CoV-2 IgG concentration were defined as "COVID-19 naïve". Anti-SARS-CoV-2 Immunoglobulin G (IgG) and SARS-CoV-2 neutralizing antibody (nAb) titers were measured to assess humoral immune response.
Anti-SARS-CoV-2 IgG titers and nAb IH% increased significantly after the first dose. The increase in antibody titers after first and second vaccination remained significant in COVID-19 naïve patients. Complete anti-SARS-CoV-2 IgG seropositivity and nAb IH% positivity was observed in all patients after the second dose. Vaccination appears to be clinically effective in IEM patients, as none of the patients had COVID-19 infection within six months of the last vaccination.
Humoral immune response after two doses of BNT162b2 in pediatric IEM patients was adequate and the immune response was not different from that of healthy individuals.
Cerebrotendinous xanthomatosis (CTX) is a lipid storage disorder caused by defective sterol 27-hydroxylase activity. In spite of subtle clinical signs beginning from childhood, CTX is generally ...diagnosed lately. The aim of this study is to evaluate clinical, neuroradiological findings and therapy responses of pediatric CTX patients and raise awareness to early features of disease. Patients who were molecularly diagnosed as CTX before 18 years of age were included in study. Clinical, epidemiological, radiological and genotypic features of patients and chenodeoxycholic acid (CDCA) therapy responses were reviewed retrospectively. Six patients were enrolled in the study. The mean age of diagnosis was 11.1 ± 4.5 years. Apart from previous studies, predominance of cerebellar signs over pyramidal signs, peripheral neuropathy with demyelinating neuropathy in majority of patients and pathological brain imaging findings despite young ages of patients were observed. Intention tremor was the consisting finding of all patients. Optic disc drusen was initially reported in one patient. Skeletal system involvement as coarse extremities, deformities and early osteoporosis was recognized in four patients. CDCA therapy improved or at least stabilized neurological functions in all patients. This study is the first CTX series from Turkey and performed among only in early diagnosed patients with a therapy follow-up contrary to limited data in the literature. We suggest that, awareness of intention tremor and ataxic gait in addition to mental retardation, peripheral neuropathy and early osteoporosis can be suspicious for CTX and lead diagnosis. Early treatment can provide stability and may also ameliorate existing neurological findings.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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