Serum procalcitonin as a marker of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD).

BACKGROUND: Neonatal Intrahepatic Cholestasis (NICCD), as the early-age stage of Citrin deficiency involving liver dysfunction, lacks efficient diagnostic markers. Procalcitonin (PCT) has been identified as a biomarker for infection as well as various organ damage. This study aimed to explore the potential of PCT as a biomarker for NICCD. METHODS: In a single-center retrospective case-control study. Serum PCT concentrations before and after treatment of 120 NICCD patients, as the study group, were compared to the same number of cholestatic hepatitis patients, as the control group. The potential value of PCT to discriminate NICCD from control disease was further explored using Receiver Operating Characteristic (ROC) curve analysis and compared to those of other inflammatory markers. RESULTS: There was a significantly higher level of PCT in NICCD patients than in the control group. PCT concentrations were only weakly correlated with neutrophil counts and CRP levels (p ˂ 0.05). At a cut-off value of 0.495 ng/mL, PCT exhibited a significantly higher diagnostic value compared to other inflammatory markers for discriminating NICCD from the control, with a sensitivity of 90.8 % and specificity of 98.3 %. CONCLUSION: PCT might be used as an initial biomarker to discriminate children with NICCD from another hepatitis disease.

Citrulinemia de presentación atípica: hipo persistente: a propósito de un caso / Citrullinemia with an atypical presentation: persistent hiccups: case report

Se informa el caso de un neonato que desarrolló encefalopatía en el transcurso de los primeros tres días de vida. Presentaba hipo persistente, que evolucionó a coma profundo 72 horas después de la admisión al hospital. Los parámetros de septicemia y el análisis del líquido cefalorraquídeo (LCR) fueron normales. Tras la evaluación metabòlica, se confirmó la presencia de hiperamoniemia e hipercitrulinemia. El índice de la concentración de LCR/glicina en plasma era normal. Esto no coincidió con nuestro diagnóstico inicial de hiperglicinemia no cetósica, que suele manifestarse con hipo. Se recomienda tener en cuenta la deficiencia de ácido argininosuccínico sintetasa (ASD por su sigla en inglés; citrulinemia) de inicio neonatal en el diagnóstico diferencial de encefalopatía asociada con hipo durante el período neonatal, lo que sugiere una enzimopatía congénita.

We report an infant who developed encephalopathy within the first 3 days of life. He had persistent hiccups that progressed to deep coma 72 hours after admission. The sepsis parameters and cerebrospinal fluid examination (CSF) were normal. The metabolic evaluation confirmed hyperammonemia, and hypercitrullinemia. The ratio of CSF/plasma glycine concentration was normal. This did not agree with our initial diagnosis of nonketotic hyperglycinemia where hiccups is present more often. Neonatal onset of argininosuccinic acid synthetase deficiency (ASD; citrullinemia) should be brought in mind in the differential diagnosis of encephalopathy in association with hiccups in the neonatal period suggesting inborn errors of metabolism.

Citrullinemia with an atypical presentation: persistent hiccups. Case report.

We report an infant who developed encephalopathy within the first 3 days of life. He had persistent hiccups that progressed to deep coma 72 hours after admission. The sepsis parameters and cerebrospinal fluid examination (CSF) were normal. The metabolic evaluation confirmed hyperammonemia, and hypercitrullinemia. The ratio of CSF/plasma glycine concentration was normal. This did not agree with our initial diagnosis of nonketotic hyperglycinemia where hiccups is present more often. Neonatal onset of argininosuccinic acid synthetase deficiency (ASD; citrullinemia) should be brought in mind in the differential diagnosis of encephalopathy in association with hiccups in the neonatal period suggesting inborn errors of metabolism.

Diagnosis of neonatal intrahepatic cholestasis caused by citrin deficiency using high-resolution melting analysis and a clinical scoring system.

OBJECTIVE: To assess the diagnosis of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) by using high-resolution melting (HRM) analysis and a clinical scoring system. STUDY DESIGN: Genetic variations in the 18 coding exons were prescreened using HRM analysis and then confirmed by direct sequencing. To establish a scoring system, clinical features of 20 patients with NICCD diagnosed in Taiwan between the years 2000 and 2008 were compared with those of 47 patients with biliary atresia and 35 with infantile cholestasis. RESULTS: Eight types of mutations/polymorphisms were identified in patients with NICCD, including 5 mutations in the coding region or splice site (c.851del4, c.1638ins23, R553Q, IVS6+5G > A, IVS11+1G > A), and 3 single-nucleotide polymorphisms (IVS11+17C > G, IVS4+6A > G/rs6957975, and c.1194A > G/rs2301629). The 3 hotspot mutations (c.851del4, c.1638ins23, and IVS6+5G > A) comprised 33/35 (94.3%) mutated alleles. The patients with NICCD had a higher frequency of the rs6957975 polymorphism compared with 103 healthy controls (P < .0001). A 6-point scoring system was proposed according to clinical parameters. The patients with NICCD tended to score ≥ 4 points, whereas biliary atresia and other infantile cholestasis tended to score <4 points (P < .0001). CONCLUSIONS: HRM analysis was efficient and effective in detecting mutations. Three common mutations comprised the majority of mutations found in our patients. The IVS4+6A > G polymorphism was associated with NICCD. A scoring system may help to differentiate patients with NICCD from those with biliary atresia.

Citrullinemia type I: molecular screening of the ASS1 gene by exonic sequencing and targeted mutation analysis.

We developed a mutation-screening protocol for the ASS1 gene in order to guide clinical management of neonates with elevated citrulline detected during routine newborn screening. An exon-based amplification and sequencing method was designed and successfully applied to patients to identify disease-associated mutations. The sequencing-based method was applied to three patients with mild or asymptomatic clinical courses. Identification of a homozygous mutation in these patients, c.787G>A (p.Val263Met), led to the development of a tetra-primer ARMS-PCR method that successfully detected the mutation in DNA extracted from blood or from Guthrie card spots.

Possible clinical and histologic manifestations of adult-onset type II citrullinemia in early infancy.

We describe 2 patients with adult-onset type II citrullinemia who developed transient hypoproteinemia and jaundice in early infancy. Liver histology showed a marked fatty change and fibrosis. After the patients had lived without symptoms to the ages of 5 and 16 years, respectively, the diagnosis was made by genetic analysis.