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Background
Neonatal physiological jaundice is a common benign condition that rarely extends behind the second week of life; however, it may interfere with the diagnosis of a pathological condition termed neonatal cholestasis (NC). The latter is a critical, uncommon problem characterized by conjugated hyperbilirubinaemia. This review aims to highlig...
Contexts in source publication
Context 1
... I (TYR-1) (hepatorenal tyrosinemia) The process of phenylalanine metabolism is illustrated in Fig. 3 [70]. Tyrosinemia (type 1-III) is an autosomal recessive disease associated with a high level of blood tyrosine [71]. The three types of the disease differ genetically, enzymatically, and clinically, and TYR-1-associated liver dysfunction is a useful differentiating point [72]. TYR-1 results in symptoms before the second year of life; ...
Context 2
... I (TYR-1) (hepatorenal tyrosinemia) The process of phenylalanine metabolism is illustrated in Fig. 3 [70]. Tyrosinemia (type 1-III) is an autosomal recessive disease associated with a high level of blood tyrosine [71]. The three types of the disease differ genetically, enzymatically, and clinically, and TYR-1-associated liver dysfunction is a useful differentiating point [72]. TYR-1 results in symptoms before the second year of life; ...
Citations
... 5 Inadequate information is available about neonatal cholestasis's epidemiology, aetiology and outcomes in Asian populations, except for countries like Taiwan and Japan. 6 Likewise, there needs to be more data about neonatal cholestasis in Pakistan, which includes clinical features of infants with neonatal cholestasis, laboratory findings, imaging studies, liver biopsies, management and short/longterm outcomes. 7 While several advancements have been made in developed countries associated with etiologies, management and revolutionizing the diagnosis of neonatal cholestasis, Pakistan faces many limitations with a huge volume of infants suffering from neonatal cholestasis. ...
Objective: To determine the frequencies of various etiologies of neonatal cholestasis diagnosed by clinical findings and laboratory investigations at the Pak Emirates Military Hospital, Rawalpindi, Pakistan. Study Design: Cross-sectional study. Place and Duration of Study: Pediatric Department of Pak Emirates Military Hospital, Rawalpindi Pakistan, from Jan 2021 to Apr 2022. Methodology: Infants of either gender aged 14 days to six months admitted to Inpatient facility who had jaundice with direct bilirubin and more than 20% of total bilirubin were included in the study. The proforma was formulated to record the clinical features, laboratory investigations, weight, level of activity and consanguinity among the parents. Results: A total of 146 infants were included in the study. Jaundice was seen in 100% of infants, hepatomegaly in 66.4%, splenomegaly in 38.4%, followed by ascites in 25%. The most common aetiology of neonatal cholestasis was Biliary Atresia 26.7% in the extrahepatic Group, Idiopathic Neonatal Hepatitis 25.3% in the intrahepatic Group. Consanguinity was present in parents of 65% of infants. Conclusion: The most common aetiology of extrahepatic Neonatal Cholestasis was Biliary Atresia, while Idiopathic Neonatal Hepatitis and Progressive Familial Intrahepatic Cholestasis were the most common causes of intrahepatic cholestasis.
... Neonatal cholestasis (NC) is a reduced bile formation or flow with retention of biliary substances inside the liver, which can be presented as conjugated hyperbilirubinemia in the first 90 days of extra-uterine life [1,2]. When conjugated serum bilirubin is greater than 20% of total bilirubin, it is a pathological condition that always requires evaluation [3][4][5][6][7]. Idiopathic neonatal hepatitis (INH) and biliary atresia (BA) are the most commonly observed causes of cholestatic jaundice in the first months of life [8,9]. ...
... A low or normal GGT suggests the presence of progressive familial intrahepatic cholestasis (PFIC type1 or PFIC type 2) [4,7,[12][13][14][15]. Abdominal ultrasonography in BA includes the triangular cord sign with non-visualized or contracted gall bladder [4][5][6][7]. Since hepatobiliary scintigraphy (HS) is not only expensive and time-consuming but also poorly specific, many centers do not routinely use this test [16][17][18][19]. ...
Background
Neonatal cholestasis (NC) is a major cause of morbidity and mortality in young infants. This study examines the etiology of NC and its outcome during 2 years of follow-up at a tertiary referral center in Bangladesh.
Results
Out of 80 cholestatic infants, 60% had intrahepatic cholestasis with a mean age of onset of 12.4±2.8 days and a mean age of admission of 82.4±29.0 days. The remaining 40% were extrahepatic with a mean age of onset of 6.7±2.3 days and a mean age of admission of 94.6±50.4 days. Biliary atresia (BA), idiopathic neonatal hepatitis (INH), and TORCH (Toxoplasma, rubella, cytomegalovirus, and herpes simplex) infection except rubella were the most common causes. After receiving treatment, 46.2% of the cases improved, 23.8% deteriorated with morbidity, and 30% died. The majority of the children with INH, TORCH, choledochal cyst, hypothyroidism, galactosemia, and urinary tract infection (UTI) with sepsis were improved. Significant mortality was found in BA (56.6%), intrahepatic bile duct paucity (PIBD) (100%), and progressive familial intrahepatic cholestasis (PFIC) (100%) whereas the rest of BA (43.4%) live with persistent morbidity. Significant clinical improvement was observed in 37 (46.2%) cases of cholestasis evidenced by decreasing jaundice, change of color of urine from dark to normal color, change of stool color from pale to yellow, and gradual decrease in liver size from hepatomegaly state. In addition, decreasing median total bilirubin, direct bilirubin, alanine transaminase, gamma-glutamyl transferase, and alkaline phosphatase showed biochemical improvement at 2 years follow-up. The age of admission, etiology, and presence of ascites are the predictors of outcomes.
Conclusion
BA was the most common cause of extrahepatic while INH and TORCH infection were the most common cause of intrahepatic cholestasis. Majority of children with intrahepatic cholestasis improved but deteriorated with BA and genetic causes. Prompt referral and early diagnosis as well as the etiology of NC were the main determinants of the favorable outcome.
... TSH, T3, T4, and cortisol levels were also normal ( Table 2). The pertinent metabolic illnesses were evaluated and found to be negative, particularly galactosemia [30] and tyrosinemia type 1 [31]. There were no anomalies observed in a thorough metabolic examination that included blood amino acid levels, urine organic acid levels, and tandem mass spectrometry ( Table 2). ...
Patient: Male, newborn
Final Diagnosis: Alagille syndrome
Symptoms: Cholestasis and/or gallbladder dysfunction
Medication: —
Clinical Procedure: —
Specialty: Genetics • Pediatrics and Neonatology
Objective
Unusual clinical course
Background
Alagille syndrome (ALGS) is a multisystem hereditary illness with a dominant pattern and partial penetrance. Multiple organ abnormalities can be caused by mutations in the Jagged canonical Notch ligand 1 (JAG1) gene. Notch receptor 2 (NOTCH2) gene mutations are also uncommon. ALGS is also characterized by deformed or narrowed bile ducts and is notoriously difficult to diagnose due to the wide range of symptoms and absence of unambiguous genotype-phenotype connections. Little is known about ALGS patients who have NOTCH2 mutations. We present a patient who developed progressive liver failure due to a unique pathogenic heterozygous variation of the NOTCH2 gene, c.1076c>T p. (Ser359Phe) chr1: 120512166, resulting in type 2 ALGS.
Case Report
A Saudi Arabian newborn with bilateral hazy eyes, ectropion, dry ichthyic skin, normal male genitalia, and bilateral undescended testes was born at 31 weeks. Previous miscarriages, pregnancy-induced maternal cholestasis, fatty liver, or neonatal jaundice were not reported in the family history. He had developed worsening cholestatic jaundice by the third week of hospitalization. The extensive work-up for metabolic, infectious, and other relevant etiologies was negative. Following gram-negative sepsis, he died of multiorgan failure. A NOTCH2 gene mutation explained the phenotypic difference in our situation. Another intriguing observation was the presence of ichthysis and craniosynostosis in ALGS with a NOTCH2 mutation.
Conclusions
Cholestasis in newborns can be difficult to diagnose. Next-generation sequencing detects 112 copy number variants in the cholestasis gene panel blood test. More research is needed to understand why NOTCH2 mutations are relatively rare in ALGS.
