İdrar Örneklerinde L-2-Hidroksiglutarik Asitin Kapiler Elektroforez-İndirekt UV Dedeksiyon ile Hızlı Tayini

Aim: L-2-hydroxyglutaric aciduria (L2HGA) which is autosomal recessive and characterized by psychomotor retardation, cerebellarataxia, variable macrocephaly, and epilepsy is a rarely seen neurometabolic disease. The disease is biochemically identified by slightlyincreased L-2HGA levels in urine, cerebrospinal fluid, and plasma.Materials and Methods: A sensitive and rapid capillary electrophoretic technique was used for the determination of L2HGA in urine.Since the L2HGA lacks of chromophore, an indirect UV detection method was applied.Results: The running electrolyte consisted of 10 mmol/L 2,6-pyridinedicarboxylic acid (PDC) at pH 5.6 containing 0.1 mmol/L ofcetyltrimethylammonium bromide (CTAB). PDC was chosen because of its good chromophoric property for indirect UV detection. CTABwas used as electro-osmotic flow (EOF) reversal. The method was well-validated in the selected conditions. The detection limit of themethod L2HGA was 1.16 ?mol/L. The migration time of L2HGA was less than 2.0 min.Conclusion: The developed method was applied to the urine samples collected from 16 patients who suffer from L-2-hydroxyglutaricaciduria and 4 healthy volunteers.Amaç: L-2 hidroksiglutarik asidüri (L2HGA) otozomal resesif geçişli, psikomotor gerilik, serebellar ataksi ve değişken makrosefali veya epilepsi ile karakterize edilen nadir görülen nörömetabolik bir hastalıktır. Hastalık biyokimyasal olarak idrarda, beyin omurilik sıvısında ve çok az miktarda plazmada artmış L-2HGA seviyeleri ile tanımlanır. Materyal ve Metot: Bu çalışmada, idrarda L-2-hidroksiglutarik asitin tayini için hızlı ve hassas bir kapiler elektroforez yöntemi geliştirilmiştir. L-2-hidroksiglutarik asit kromofor gruba sahip olmadığı için, indirekt UV deteksiyon metodu uygulanmıştır. Bulgular: Çalışma tamponu pH 5.6’da 0.1 mmol/L setiltrimetilamonyum bromür (CTAB) içeren 10 mmol/L 2,6-piridindikarboksilik asitten (PDC) oluşmaktadır. PDC iyi bir kromoforik özellik göstermesinden dolayı indirekt deteksiyon için uygundur. CTAB elektro-osmotik akışı (EOF) ters çevirmek için kullanılmıştır. L-2-hidroksiglutarik asit için tayin limiti 1.16 ?mol/L’dir. Geliş zamanı ise 2.0 dakikadan daha az bir süredir. Sonuç: Geliştirilen metod 16 L-2-hidroksiglutarik asidüri hastasından ve 4 sağlıklı gönüllüden toplanan idrar örneklerine uygulanmıştır

A New Mutation in Diagnosis of Wolman Disease: Case Report

Wolman hastalığı kolesterol ester ve trigliseridlerin hidrolizinden sorumlu lizozomal asit lipaz (LAL) enzim aktivitesindeki kayıp sonucunda ortaya çıkar. Kusma, ishal, azalmış tartı alımı, hepatomegali ile karakterize olup erken süt çocukluğu döneminde ölümle sonuçlanır. Hastalığın kesin tanısı LIPA geninin moleküler analizi ile konulur. LIPA genine ait nokta mutasyonlar, insersiyon ve delesyonlar gibi farklı mutasyonlar bildirilmiş olup, Wolman hastalığında çerçeve kayma mutasyonları nadiren görülmektedir.Bu yazıda LIPA gen analizi ile Wolman hastalığının kesin tanısı konulan 18 günlük bir kız hasta sunulmuştur. Moleküler analiz sonucunda literatürde daha önce bildirilmemiş bir çerçeve kayma mutasyonu saptanmıştır.Wolman disease (WD) is caused by the complete loss of lysosomal acid lipase (LAL) activity that is essential for hydrolysis of cholesterol esters and triglycerides. It presents with vomiting, diarrhea, poor weight gain, and hepatomegaly subsequently leading to death in infancy. Definite diagnosis is based on genetic confirmation by the LIPA gene sequencing. Several types of mutations, including point mutations, insertions, and deletions, have been reported in LIPA gene. Frameshift mutations are not frequently showed in WD. Here, an 18-day-old female patient in whom the definite diagnosis was made by the LIPA gene sequencing is reported. Genetic analysis resulted in a novel frameshift mutation that has not been reported before

COVID-19 triggered encephalopathic crisis in a patient with glutaric aciduria type 1

Objectives: The impact of coronavirus disease-19 (COVID-19) on metabolic outcome in patients with inborn errors of metabolism has rarely been discussed. Herein, we report a case with an acute encephalopathic crisis at the course of COVID-19 disease as the first sign of glutaric aciduria type 1 (GA-1). Case presentation: A 9-month-old patient was admitted with encephalopathy and acute loss of acquired motor skills during the course of COVID-19 disease. She had lethargy, hypotonia, and choreoathetoid movements. In terms of COVID-19 encephalopathy, the reverse transcriptionpolymerase chain reaction assay test for COVID-19 was negative in cerebral spinal fluid. Brain imaging showed frontotemporal atrophy, bilateral subcortical and periventricular white matter, basal ganglia, and thalamic involvement. Elevated glutarylcarnitine in plasma and urinary excretion of glutaric and 3-OH-glutaric acids was noted. A homozygote mutation in the glutaryl-CoA dehydrogenase gene led to the diagnosis of GA-1. Conclusions: With this report, neurological damage associated with COVID-19 has been reported in GA-1 patients for the first time in literature

Challenges of following patients with inherited metabolic diseases during the COVID-19 outbreak. A cross-sectional online survey study

Objectives: There has been a recent worldwide outbreak of coronavirus disease (COVID-19). Most of the health system capacity has been directed to COVID-19 patients, and routine outpatient clinics have been suspended. Chronic disease patients, such as inherited metabolic disorders (IMD), have had trouble accessing healthcare services

Impact of sodium phenylbutyrate treatment in acute management of maple syrup urine disease attacks: a single-center experience

Objectives: Accurate management of metabolic decompensation in maple syrup urine disease (MSUD) has a crucial role, as acute attacks can cause neurological sequels and can be life threatening. Here, we aimed to evaluate effect of sodium phenylbutyrate (NaPBA) in acute management of MSUD attacks

Evaluation of plasma carnitine status in patients diagnosed with juvenile idiopathic arthritis

Background/aim: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood and manifests mainly as autoinflammation of the joints and other tissues. Several treatment options such as nonsteroidal antiinflammatory drugs, methotrexate, and intra-articular steroids are widely used to relieve and improve this inflammation. Secondary carnitine deficiency can be detected in chronic diseases by either renal loss or increased demand. While carnitine status can be associated with several conditions, in the present study our aim is to determine the levels of free carnitine and acyl-carnitine in Turkish JIA patients. Materials and methods: One hundred and fourteen patients diagnosed with juvenile idiopathic arthritis and 50 healthy individuals who served as the control group were included in the study. A fasting blood sample was collected from the children in both groups to determine free carnitine and acylcarnitine ester by quadripole electrospray tandem mass spectrometry (ESI-MS/ MS). Results: Screening of acyl-carnitine profile revealed free carnitine, C14, C14:2, C16, C16-OH, and C18 carnitine levels were higher (p < 0.0001, p < 0.0001, p < 0.001, p < 0.001, and p = 0.011, respectively), while C2, C3, C4, C6, C8, C10, C10:1, C10:2, C3DC, C4DC, C5DC, C4-OH, and C18:1-OH carnitine levels were lower (p < 0.0001) in JIA patients in comparison to the control group. Total acyl-carnitine levels (p < 0.001) and acyl-carnitine to free carnitine ratio (p < 0.001) were also lower in JIA patients than the control group. Free carnitine levels were significantly higher (48.05 ?? 13.36 ??mol/L) in patients under antiinflammatory drug therapy than those who did not receive any treatment (43.18 ?? 7.96 ??mol/L) (p = 0.004). Conclusion: In the present study we were not able to define secondary carnitine deficiency in JIA patients, although free carnitine and acyl-carnitine variations were detected in JIA patients. In conclusion, routine carnitine supplementation is not recommended in all patients with JIA

Long-term N-carbamylglutamate treatment of hyperammonemia in patients with classic organic acidemias

Background: Classic organic acidurias (OAs) usually characterized by recurrent episodes of acidemia, ketonuria, and hyperammonemia leading to coma and even death if left untreated. Acute hyperammonemia episodes can be treated effectively with N-carbamylglutamate (NCG). The effect of the long-term efficacy of N-carbamylglutamate is little known

Postural tremor in L-2-hydroxyglutaric aciduria is associated with cerebellar atrophy

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

Inborn errors of metabolism and coronavirus disease 2019: Evaluation of the metabolic outcome

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