Interpretation of alpha-fetoprotein concentrations in cerebrospinal fluid of infants

Coakley, John; Kellie, SJ; Nath, Christa E.; Munas, Azhar; Cooke‐Yarborough, Claire

doi:10.1258/0004563053026763

Cited by 12 publications

(13 citation statements)

References 14 publications

(15 reference statements)

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“…The serum levels of alpha-fetoprotein (AFP) were dramatically elevated in both patients. It was well known that serum AFP levels in newborns at birth was very high, with a reference interval of 15700–146,500 ng/ml and a medium value of 48,300 ng/ml [ 22 ], which then decreased dramatically with the increased age, and reached the childhood or adulthood reference range by around 6 weeks [ 23 ] to 8 months [ 24 ], and even by 3 years of age [ 25 ]. The age-dependant wide variation range of AFP levels indicated that there must be more than one unknown factor affecting the AFP serum level [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Sodium taurocholate cotransporting polypeptide (NTCP) deficiency: Identification of a novel SLC10A1 mutation in two unrelated infants presenting with neonatal indirect hyperbilirubinemia and remarkable hypercholanemia

et al. 2017

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Sodium taurocholate cotransporting polypeptide (NTCP) is encoded by the gene SLC10A1 and expressed in the basolateral membrane of the hepatocyte, functioning to uptake bile acids from plasma. Although SLC10A1 has been cloned and NTCP function studied intensively for years, clinical description of NTCP deficiency remains rather limited. This study reported the genotypic and phenotypic features of two neonatal patients with NTCP deficiency. They both presented with neonatal indirect hyperbilirubinemia and remarkable hypercholanemia, and harbored the SLC10A1 variants c.800C>T (p.S267F) and c.263T>C (p.I88T). On genetic analysis of the two family trios, the latter missense variant was detected in trans with the former, a reported loss-of-function variant. Having not been reported in any databases, the c.263T>C (p.I88T) variant demonstrated an allele frequency of 0.67% (1/150) in healthy controls. Moreover, this variant involved a relatively conservative amino acid, and was predicted to be pathogenic or deleterious by changing the conformation of the NTCP molecule. In conclusion, the novel variant c.263T>C (p.I88T) in this study enriched the SLC10A1 mutation spectrum; the clinical findings lent support to the primary role of NTCP in hepatic bile acid clearance, and suggested that NTCP deficiency might be a contributing factor for the development of neonatal indirect hyperbilirubinemia.

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Section: Discussionmentioning

confidence: 99%

Sodium taurocholate cotransporting polypeptide (NTCP) deficiency: Identification of a novel SLC10A1 mutation in two unrelated infants presenting with neonatal indirect hyperbilirubinemia and remarkable hypercholanemia

et al. 2017

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“…Five additional publications were retrieved from the references of those papers. A total number of 24 papers was therefore identified: 22 experimental studies [10,11,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] (one including two substudies [38]) and two abstracts from poster presentations [41,42]. The main features of the selected studies are reported in Table 1.…”

Section: Data Sources and Searchesmentioning

confidence: 99%

“…Looking at AFP concentrations alone could not reliably exclude tumors in infants, and often, histologic detection and imaging should be prioritized [5,8,9]. In general, there is an agreement about the low capability of AFP to rule out malignancy in preterm and term infants up to 4 months of age, as available upper reference limits (URL) look unreliable and unsuitable for clinical application [1,11]. Practical indications about the AFP use in young infants are therefore retrieved from literature based on registries/retrospective case series collected in years of clinical experience [12][13][14][15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Serum α-fetoprotein in pediatric oncology: not a children’s tale

Ferraro

Panzeri

Braga

et al. 2018

Clinical Chemistry and Laboratory Medicine (CCLM)

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Background Measurement of α-fetoprotein (AFP) concentrations in the serum of infants is useful for the management of testicular germ cell tumors, hepatoblastoma and hepatocellular carcinoma. Here, we provide a critical review of the available information about pediatric reference intervals (RI), focusing on their utility in interpreting AFP as an aid for cancer diagnosis. Content Evidence sources in the available literature were critically appraised. Out of 3873 retrieved papers, 24 were finally selected and carefully inspected, and six of them overcame exclusion criteria (i.e. methodological limitations in the study design, statistical gaps, drawbacks in traceability of the AFP assay to higher order materials and/or biased reporting of AFP results). Preterm and term infants up to the 3rd month of life exhibited the highest average AFP concentrations, but the attempt of defining RI by data pooling and partitioning for age intervals was impeded by the wide variability of data. The inability of defining robust RI in the first months of life made difficult, if not impossible, using upper reference limits for ruling out malignancies with a single AFP result. Evaluating the behavior of AFP concentrations 5 days from the baseline result, if this exceeds risk thresholds partitioned for age, according to the formula Xt=X0*2−t/HL (where: t=days elapsed for AFP retest; HL=AFP half-life according to age; X0=AFP baseline concentration, and Xt=predicted AFP concentration at day 5), could give a better information. Summary Novel studies defining AFP RI in infants based on robust methodology are warranted to improve the interpretation of AFP results in pediatric oncology. In the meantime, algorithms based on both serum AFP absolute concentrations and HL may aid in cancer diagnosis.

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“…Tumor markers have been identified for a variety of cancers and integrated into the diagnosis and management of patients with these cancers [17]. AFP is a 70 kDa glycoprotein normally secreted by the fetus primarily in the yolk sac, gastrointestinal tract, and liver [4, 5]. bHCG is a 36.7 kDa glycoprotein normally secreted by placental tissues [17].…”

Section: Introductionmentioning

confidence: 99%

“…Elevated serum or CSF concentrations of AFP are strong predictors of NGGCTs [7], as are high concentrations ob bHCG; however, the latter can be mildly to moderately increased in germinomas [7]. AFP is a 70 kDa glycoprotein normally secreted by the fetus primarily in the yolk sac, gastrointestinal tract, and liver [4, 5]. Since AFP concentrations normally drop to adult levels by 1 year of life, elevated levels in adolescents and adults can be indicative of malignancy [9].…”

Section: Introductionmentioning

confidence: 99%

Diagnostic utility and correlation of tumor markers in the serum and cerebrospinal fluid of children with intracranial germ cell tumors

Qaddoumi

Sane

et al. 2012

Childs Nerv Syst

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Purpose In order to predict whether tumor markers assist in the histopathologic diagnosis of germ cell tumors (GCTs), we analyzed the correlation of beta human chorionic gonadotropin (bHCG) and alpha-fetoprotein (AFP) in serum and cerebrospinal fluid (CSF) samples at baseline and subsequent follow-up examinations. Method A retrospective study of patients diagnosed with intracranial GCTs between July 1985 and February 2011 at our institution was conducted to review clinical, surgical, radiological, laboratory and histopathologic data. Results Of 67 patients eligible for the study, 42 had germinomas and 25 non germinomatous GCTs. At baseline, serum and CSF AFP agreed in 97.9% of patients (Cohen’s Kappa 0.93). Baseline bHCG samples agreed in only 72.5% of patients (Cohen’s Kappa 0.46). In most cases, values were higher in serum for AFP and in CSF for bHCG. ROC curves estimated from logistic regression model indicated that CSF and serum samples had almost equal diagnostic utility, and the DeLong test showed that the difference in area under curves was not statistically significant. During follow-up (185 paired CSF and serum values from 43 patients), 90.3% of AFP values correlated between CSF and serum (Cohen’s Kappa 0.22, showing fair agreement). For bHCG, 96.2% of values agreed in serum and CSF (Cohen’s Kappa 0.61). Conclusions In some patients, intracranial GCTs can be diagnosed based solely upon positive serum AFP values. In addition, marker values from serum only may be sufficient to predict tumor relapse at interval follow-up examinations.

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Interpretation of alpha-fetoprotein concentrations in cerebrospinal fluid of infants

Cited by 12 publications

References 14 publications

Sodium taurocholate cotransporting polypeptide (NTCP) deficiency: Identification of a novel SLC10A1 mutation in two unrelated infants presenting with neonatal indirect hyperbilirubinemia and remarkable hypercholanemia

Sodium taurocholate cotransporting polypeptide (NTCP) deficiency: Identification of a novel SLC10A1 mutation in two unrelated infants presenting with neonatal indirect hyperbilirubinemia and remarkable hypercholanemia

Serum α-fetoprotein in pediatric oncology: not a children’s tale

Diagnostic utility and correlation of tumor markers in the serum and cerebrospinal fluid of children with intracranial germ cell tumors

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