Combined primary carnitine deficiency with neonatal intrahepatic cholestasis caused by citrin deficiency in a Chinese newborn

Lin, Yiming; Lin, Weihua; Chen, Yanru; Cai, Lin; Zheng, Zhiyong; Zhuang, Jianlong; Fu, Qingliu

doi:10.1186/s12887-020-02372-7

Cited by 6 publications

(5 citation statements)

References 23 publications

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“…NBS for PCD was performed using tandem mass spectrometry (MS/MS), by measuring free carnitine (C0) levels below the cut-off value in dried blood spot samples. The diagnosis of PCD after NBS is confirmed by genetic analysis of the SLC22A5 gene or by verifying reduced carnitine transport activity in fibroblasts [ 8 , 9 ]. The measurement of carnitine transport activity is a reliable diagnostic assay, but it is only performed in a few laboratories worldwide and requires a skin biopsy.…”

Section: Introductionmentioning

confidence: 99%

Biochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screening

Lin¹,

Lin²,

Chen³

et al. 2021

Orphanet J Rare Dis

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Background Primary carnitine deficiency (PCD) is an autosomal recessive disorder of carnitine transportation that leads to impaired fatty acid oxidation. Large-scale studies on newborn screening (NBS) for PCD are limited. This study aimed to investigate the biochemical and genetic characteristics of patients with PCD detected through NBS. Results A total of 548 247 newborns were screened for PCD between January 2014 and June 2021; 1714 newborns with low free carnitine (C0) levels were called back and 49 patients were diagnosed with PCD. The latest incidence rate in Quanzhou, China, was estimated to be 1 in 11 189 newborns. NBS results showed that the 49 patients had varying degrees of decreased C0 levels, whereas seven patients exhibited normal C0 levels during the recall review. All patients harbored biallelic pathogenic variants of the SLC22A5 gene. Nineteen distinct SLC22A5 variants were detected in these 49 patients, and most of the detected variants were clustered in exons 1, 4, and 7. The top eight variants had an allele frequency of 86.73%. The most common variant was c.760C > T (p.R254*) with an allele frequency of 31.63%, followed by c.51C > G (p.F17L) (17.35%) and c.1400C > G (p.S467C) (16.33%). The C0 level of patients with the N/N genotype was significantly lower than that of the M/M group. The C0 levels of patients with genotypes of R254*/R254* and R254*/F17L were far lower than those of patients with the R254*/S467C genotype. Conclusions This study presented more than 500,000 NBS data with the latest incidence of 1:11 189 in the Quanzhou area. The SLC22A5 variant spectrum in the selected southern Chinese population has been updated. Patients with null variants were associated with low C0 levels. Combining NBS with genetic testing is critical to improve screening efficiency because patients with PCD may have normal C0 levels during NBS and recall review.

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Section: Introductionmentioning

confidence: 99%

Biochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screening

Lin¹,

Lin²,

Chen³

et al. 2021

Orphanet J Rare Dis

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“…Of the symptomatic maternal cases (17/102; 16.7%), nine experienced exclusively pregnancy‐related/nonspecific symptoms (see Table 2) and eight patients developed the following symptoms: VF and hypotonia ( N = 1; 1.0%), sus‐VT ( N = 1; 1.0%), cardiomyopathy with cardiac dilation ( N = 1; 1.0%), hepatic steatosis with hypoglycemia ( N = 1; 1.0%), muscle weakness ( N = 3; 3.9%), and fasting intolerance ( N = 1; 1.0%). The signs and symptoms in NBS patients (25/249; 10.0%) were, respectively: nonspecific ( N = 11), cardiac involvement ( N = 4; atrial/ventricular septal defect and/or mitral valve insufficiency), metabolic signs ( N = 1; metabolic decompensation), metabolic signs and neurological symptoms ( N = 3; hypoglycemia and coma/convulsions), hepatic symptoms ( N = 1; elevated alanine aminotransferase (ALAT)), muscle symptoms ( N = 2; mild muscle weakness, elevated creatine kinase), and death ( N = 3) 6,27‐32 . In patients identified through high‐risk screening, the majority of individuals did not experience any (PCD‐related) symptoms (30.3% asymptomatic and 44.0% only nonspecific symptoms).…”

Section: Resultsmentioning

confidence: 99%

“…The signs and symptoms in NBS patients (25/249; 10.0%) were, respectively: nonspecific ( N = 11), cardiac involvement ( N = 4; atrial/ventricular septal defect and/or mitral valve insufficiency), metabolic signs ( N = 1; metabolic decompensation), metabolic signs and neurological symptoms ( N = 3; hypoglycemia and coma/convulsions), hepatic symptoms ( N = 1; elevated alanine aminotransferase (ALAT)), muscle symptoms ( N = 2; mild muscle weakness, elevated creatine kinase), and death ( N = 3). 6 , 27 , 28 , 29 , 30 , 31 , 32 In patients identified through high‐risk screening, the majority of individuals did not experience any (PCD‐related) symptoms (30.3% asymptomatic and 44.0% only nonspecific symptoms). But the prevalence of severe symptoms (cardiomyopathy, cardiac events, and sudden death) was higher in this group than in patients identified through newborn screening (NBS and maternal cases).…”

Section: Resultsmentioning

confidence: 99%

Clinical characteristics of primary carnitine deficiency: A structured review using a case‐by‐case approach

Crefcoeur

Visser

Ferdinandusse

et al. 2022

J of Inher Metab Disea

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A broad spectrum of signs and symptoms has been attributed to primary carnitine deficiency (PCD) since its first description in 1973. Advances in diagnostic procedures have improved diagnostic accuracy and the introduction of PCD in newborn screening (NBS) programs has led to the identification of an increasing number of PCD patients, including mothers of screened newborns, who may show a different phenotype compared to clinically diagnosed patients. To elucidate the spectrum of signs and symptoms in PCD patients, we performed a structured literature review. Using a case‐by‐case approach, clinical characteristics, diagnostic data, and mode of patient identification were recorded. Signs and symptoms were categorized by organ involvement. In total, 166 articles were included, reporting data on 757 individual patients. In almost 20% (N = 136) of the cases, the diagnosis was based solely on low carnitine concentration which we considered an uncertain diagnosis of PCD. The remaining 621 cases had a diagnosis based on genetic and/or functional (ie, carnitine transporter activity) test results. In these 621 cases, cardiac symptoms (predominantly cardiomyopathy) were the most prevalent (23.8%). Neurological (7.1%), hepatic (8.4%), and metabolic (9.2%) symptoms occurred mainly in early childhood. Adult onset of symptoms occurred in 16 of 194 adult patients, of whom 6 (3.1%) patients suffered a severe event without any preceding symptom (five cardiac events and one coma). In conclusion, symptoms in PCD predominantly develop in early childhood. Most newborns and mothers of newborns detected through NBS remain asymptomatic. However, though rarely, severe complications do occur in both groups.

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“…e combined evaluation also showed that, after 10-fold cross-validation, done three times for 97 samples, the average reliability could reach 95.8 percent. is accuracy rate has been comparable to that of methods frequently employed in clinical settings; multi-mode ultrasound (US) has an accuracy of roughly 71.7% [24], while MRI has attained an 80% accuracy for diagnostic purposes [25]. As a result, PA spectroscopy's efficiency for diagnosing prostate cancer using the LDA technique is on par with that of US and MRI.…”

Section: Prostate Cancer Identification Through Svm Nb C45 and Ldamentioning

confidence: 92%

Implementation of Machine Learning Mechanism for Recognising Prostate Cancer through Photoacoustic Signal

Ramkumar

Bhuvaneswari

Radhika³

et al. 2022

Contrast Media & Molecular Imaging

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Biological tissues may be studied using photoacoustic (PA) spectroscopy, which can yield a wealth of physical and chemical data. However, it is really challenging to directly analyse these tissues because of a lot of data. Data mining techniques can get around this issue. In order to diagnose prostate cancer via PA spectrum assessment, this work describes the machine learning (ML) technique implementation, such as supervised classification and unsupervised hierarchical clustering. The collected PA signals were preprocessed using Pwelch method, and the features are extracted using two methods such as hierarchical cluster and correlation assessment. The extracted features are classified using four ML-methods, namely, Support Vector Machine (SVM), Naïve Bayes (NB), decision tree C4.5, and Linear Discriminant Analysis (LDA). Furthermore, as these components alter throughout the progression of prostate cancer, this study focuses on the composition and distribution of collagen, lipids, and haemoglobin. In diseased tissues compared to normal tissues, there is a stronger correlation between the various chemical components ultrasonic power spectra, suggesting that the microstructural dispersion in tumour tissues has been more uniform. The accuracy of several classifiers used in cancer tissue diagnosis was greater than 94% for all four methods, which is effective than that of benchmark medical methods. Thus, the method shows significant promise for the noninvasive, early detection of severe prostate cancer.

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Combined primary carnitine deficiency with neonatal intrahepatic cholestasis caused by citrin deficiency in a Chinese newborn

Cited by 6 publications

References 23 publications

Biochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screening

Biochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screening

Clinical characteristics of primary carnitine deficiency: A structured review using a case‐by‐case approach

Implementation of Machine Learning Mechanism for Recognising Prostate Cancer through Photoacoustic Signal

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