Neonatal Cholestatic Jaundice Research Articles

One case of arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome featuring an incomplete and mild phenotype

BackgroundArthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare disease with a high mortality rate caused by VPS33B or VIPAS39 mutations. ARC syndrome typically presents with arthrogryposis, renal tubular leak and neonatal cholestatic jaundice, and most patients with this disease do not survive beyond one year.Case presentationHere, we report the case of a 13-year-old girl with ARC featuring an incomplete and mild phenotype with novel compound heterozygous mutations of VPS33B. The patient presented with arthrogryposis (claw-shaped limbs), ichthyosis, jaundice, and pruritus. Laboratory tests revealed highly evaluated levels of total bilirubin (TB), direct bilirubin (DB), and total bile acid (TBA) as well as normal levels of gamma-glutamyltransferase (GGT). However, signs of renal dysfunction, as well as other manifestations of ARC syndrome, including nervous system abnormalities, deafness, and failure to thrive, were not observed. The patient’s clinical symptoms of jaundice and pruritus were significantly alleviated by administration of ursodeoxycholic acid. Whole-exome sequencing (WES) revealed novel compound heterozygous mutations of VPS33B, c.1081 C > T (p.Q361X,257)/c.244 T > C (p.C82R). Both variants were predicted to be pathogenic in silico and have never been reported previously. To date, the patients’ cholestatic jaundice has been well controlled with continuous treatment of ursodeoxycholic acid.ConclusionsWe report the case of a Chinese female with ARC including novel compound heterozygous mutations of VPS33B and an incomplete and mild phenotype. Early diagnosis and suitable symptomatic therapies are critical for the management of ARC patients with mild manifestations and prolonged lifespan.

Conjugated hyperbilirubinemia among infants with hyperinsulinemic hypoglycemia.

From clinical practice, we noted that a subset of neonates with hyperinsulinism develop conjugated hyperbilirubinemia. A relationship between these two conditions has not been previously described. We aimed to assess the incidence of cholestasis in a cohort of neonates with hyperinsulinism and describe their clinical characteristics. In a retrospective cohort of 63 neonates with hyperinsulinism, 48% developed cholestasis (conjugated bilirubin > 17 μmol/L) with a median maximum conjugated bilirubin of 81 [21 to 191] μmol/L. A history of fetal distress (RR 2.3 [1.24-4.45], p < 0.01) and prematurity (RR 2.0 [1.23-3.26], p <0.01) was associated with the development of cholestasis, but not parental nutrition or other pharmacological treatments. An underlying etiology for the cholestasis was only found in 1 patient, and in all cases the cholestasis spontaneously improved.Conclusions: A significant percentage of infants with hyperinsulinism develop idiopathic, spontaneously resolving, conjugated hyperbilirubinemia. The association with a history of fetal distress potentially suggests that intrauterine factors leading to hyperinsulinism may also predispose towards conjugated hyperbilirubinemia. While the presence of neonatal cholestatic jaundice warrants timely investigations to exclude important underling etiologies, if validated, these findings may support a less invasive diagnostic workup of conjugated hyperbilirubinemia in infants with co-existent hyperinsulinism. What is Known: • Hyperinsulinism and conjugated hyperbilirubinemia are two common presentations in neonates. • A clinical association between the two conditions has not been described. What is New: • A significant proportion of infants with hyperinsulinism develop idiopathic, spontaneously resolving conjugated hyperbilirubinemia. • Increased risk for cholestasis in this patient population is associated with fetal distress and prematurity but not parental nutrition.

Green Pigmentation of Teeth Caused by Neonatal Cholestatic Jaundice and Sepsis: A Case Report

ABSTRACTAimThe aim of this article is to report a case of green discoloration of primary teeth associated with neonatal cholestatic jaundice and sepsis in a 2-year-old girl.BackgroundSystemic changes can lead to dental alterations of the teeth. One of the disorders is elevated serum bilirubin levels that can cause pigmentation of teeth. Green pigmentation of teeth is uncommon, but when it occurs, is a cause of concern for parents and the child, as he may also loose self-confidence.Case descriptionThe parents reported to the clinic with the child whose chief complaint was green pigmented teeth. Her medical records revealed she was preterm and was diagnosed with neonatal cholestatic jaundice which lead to hyperbilirubinemia and sepsis. On review at 36 months of age, all her deciduous teeth were completely erupted and a striking demarcation was visible between the green incisal edges and the normally colored cervical one-thirds of all primary teeth. Treatment alternatives were suggested and the child was kept on regular follow-ups.ConclusionSo, one should be aware of such condition and seek medical practitioner or reports to confirm the diagnosis. If such a condition exists, esthetic treatment can be achieved with the newer techniques in cosmetic dentistry.Clinical significanceGreen pigmentation has very limited causes. The time of illness coincides with the stage of tooth formation. Proper medical history is important to evaluate the extent of pigmentation and probable involvement of the permanent teeth.How to cite this articleLamba G, Nagpal DI, Korishettar R. Green Pigmentation of Teeth Caused by Neonatal Cholestatic Jaundice and Sepsis: A Case Report. Int J Clin Pediatr Dent 2019;12(6):566–568.

Clinical features and gene mutation analysis of patients with Niemann-Pick disease type C

Objective: To analyze the clinical manifestations, therapeutic efficacy, prognosis and characteristics of NPC1 mutation in Chinese patients with Niemann-Pick disease type C(NPC). Methods: Ten unrelated Chinese NPC patients were diagnosed by NPC1 mutation analysis from July 2013 to February 2017 in Beijing Tian Tan Hospital of Capital Medical University. Clinical data of 10 cases were analyzed retrospectively which included clinical manifestations, laboratory results and NPC1 gene mutation features, and a series of follow-up were carried out about therapeutic efficacy and prognosis. Results: Ten patients suffering from NPC included 5 males and 5 females, aged from 42 days to 14 years when they presented to Tian Tan Hospital. According to their age of neurological onset, 4 were in early infantile period, 2 in late infantile period, 2 in juvenile periods, and the other 2 cases in neonatal period. They all presented with splenomegaly, 5 of 10 accompanied with hepatomegaly. Two cases of neonatal subtype presented mainly with delayed neonatal cholestatic jaundice and hepatosplenomegaly, accompanied with decreased muscle tone and slight psychomotor retardation. The other 8 cases presented with severe neurological involvement, such as progressive encephalopathy, ataxia and language impairment, 4 with dystonia, 3 with decreased muscle tension, 5 with vertical supranuclear gaze palsy, 5 with gelastic cataplexy, and 4 with epilepsy. Eight of 9 cases presented with foam cells in their bone marrow. Head MRI showed diffuse cerebral atrophy in 8 cases, thin corpus callosum in 2 cases, and brain white matter abnormal signals in 2 cases. Among 10 cases, 18 different mutations of NPC1 allelic genes were identified including 11 reported mutations, 3 novel missense mutations: c. 3683T>C (p.Met1128Thr), c.1926G>C (p.Met642Iie) and c. 3006C>G (p.Phe1002Leu), 2 novel nonsense mutation: c. 1142G>A(p.Trp381Ter ) and c. 3229C>T(p.Arg1077Ter), 1 novel minimal deletion mutation: c. 1385-1386del, and 1 novel intron mutation: c. 1757+ 5G>A. In 5 cases, the symptom of gelastic cataplexy was alleviated by imipramine, and the convulsion was relieved by valproate in 2 cases, by carbamazepine in 1 case at the beginning of seizure. During the 25 (3-66) months of follow-up, 4 cases died, the others' neurological symptoms were deteriorated progressively. Conclusions: The NPC1 gene mutation were high heterozygous in this group, and 7 novel mutations enriched the gene mutation spectrum of NPC1. The neurological manifestations were complicated in patients with NPC, and the symptomatology would be different according to their onset age of neurological symptoms. There might be effective symptomatic treatment for gelastic cataplexy by imipramine and for convulsion by valproate or carbamazepine.

Clinical features, outcomes, and genetic analysis in Korean children with Alagille syndrome.

Alagille syndrome (AGS) is a multisystem autosomal dominant disorder that affects the liver, heart, eyes, face, bone, and other organs. AGS is caused by mutations in one of two genes, JAG1 or NOTCH2. We evaluated clinical features, outcomes, and the presence of JAG1 and NOTCH2 mutations in Korean children with AGS. Between January 1997 and December 2013, 19 children were diagnosed with AGS at Asan Medical Center, Seoul, Korea. Their clinical features, outcomes, and JAG1 and NOTCH2 mutation status were retrospectively analyzed. The prevalence of clinical features in the 19 patients was as follows: dysmorphic facial features, 100% (n = 19); liver symptoms, 89% (n = 17); cardiac symptoms, 95% (n = 18); ophthalmologic symptoms, 67% (n = 10); skeletal deformities, 47% (n = 9); and renal symptoms, 21% (n = 4). JAG1 mutations were identified in 14 patients. The 13 different JAG1 mutations, seven of which were novel, included four deletions, three insertions, two missense mutations, three nonsense mutations, and one indel mutation. No NOTCH2 mutations were found. Two patients who received liver transplantation due to liver failure were still alive. Two patients died of comorbidities related to AGS: one of cardiac failure and one of hepatic failure. This study describes the clinical characteristics of 19 Korean AGS patients with seven novel JAG1 mutations. Neonatal cholestatic jaundice was the most common initial presenting symptom; thus the presence of neonatal cholestasis warrants screening for syndromic features of AGS. Complex heart anomalies and progressive liver dysfunction resulted in significant morbidity and mortality in AGS.

A suspicion index for early diagnosis and treatment of cerebrotendinous xanthomatosis

Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid storage disorder characterized by a heterogeneous presentation and a broad spectrum of clinical manifestations. Since early diagnosis and replacement therapy with chenodeoxycholic acid can prevent clinical deterioration, our aim was to develop a diagnostic tool to identify and treat CTX patients at an initial stage of the disease. We devised a suspicion index, composed of weighted scores assigned to indicators such as family history characteristics and common systemic and neurological features, on the basis of a pooled analysis of selected international CTX series. The indicators were classified as very strong (score 100), strong (50) or moderate (25). The suspicion index was then applied retrospectively to our CTX population. Early systemic signs such as cataract, diarrhea and neonatal cholestatic jaundice were considered strong indicators, together with neurological features such as intellectual impairment, psychiatric disturbances, ataxia, spastic paraparesis and dentate nuclei abnormalities at MRI. Tendon xanthomas were regarded as very strong indicators, as was an affected sibling. A total score ≥ 100 warranted serum cholestanol assessment. Elevated cholestanol or a total score ≥ 200, with one very strong or four strong indicators, warranted CYP27A1 gene analysis. In our patients, age at diagnosis was 35.5 ± 11.8years (mean ± standard deviation), whereas with the diagnostic tool it became 10.6 ± 9.8years (p < 0.01). Our suspicion index provides a simple and inexpensive diagnostic tool allowing diagnosis and treatment of CTX before neurological disability occurs.

Platelet Functional and Morphological Abnormalities In a Case Of Arthrogryposis, Renal Dysfunction and Cholestasis (ARC) Syndrome With a Novel Genetic Profile

ARC syndrome is a severe autosomal recessive multisystem disorder characterized by arthrogryposis, neonatal cholestatic jaundice, renal tubular acidosis, failure to thrive, dysmorphic features, congenital heart disease, cerebral malformation, hypotonia, recurrent febrile illness and a bleeding disorder. It is associated with consanguinity and most patients do not survive beyond the first year of life. ARC syndrome is linked to loss of function in either VPS33B or VIPAS39, respectively encoding VPS33B and VPS16B, which we have shown to be interaction partners within a multiprotein complex involved in intracellular vesicular trafficking (Urban et al, Blood. 2012 Dec 13;120(25):5032-40). Earlier we determined that bleeding problems in ARC syndrome patients (where platelet aggregation abnormalities have been observed) arise from abnormal function of normally abundant platelets lacking α-granules (Lo et al, Blood. 2005;106(13):4159-66). Detailed studies of ARC syndrome platelets have been hampered by limited availability.A term 4-month old boy was observed to have significant epistaxis and petechiae requiring multiple transfusions of plasma, packed red blood cells, tranexamic acid, vitamin K and nasal packing twice, with final success over control of bleeding. INR was 1.8 and PTT was 40 with a normal platelet count of 319 during this episode. Intermittent episodes of bleeding continued throughout his course, with difficulty in stopping the bleeding. The patient was found to have jaundice with scleral icterus, cholestasis and giant cell hepatitis seen on liver biopsy. A metabolic work-up revealed significant aminoaciduria and proximal tubular acidosis. He also had failure to thrive, feeding intolerance, severe bilateral sensorineural hearing loss, limb contractures, right rocker bottom foot and clubbed left foot. MRI of the brain showed abnormal corpus callosum with non-visualization of the anterior commissure. On abdominal ultrasound, the liver was enlarged and mildly echogenic with no evidence of portal hypertension and patent vessels. Echogenic kidneys were present with nephrocalcinosis. He was referred for evaluation and possible liver transplantation.Blood film examination revealed pale-appearing platelets and transmission electron microscopy confirmed the complete absence of α-granules, making a diagnosis of ARC syndrome highly probable. Immunofluorescence confocal microscopy detected abnormalities in patient platelets with regards to: 1) size (larger than normal); 2) morphology of the tubulin ring cytoskeleton (loosely organized compared to normal); and 3) intracellular distribution of CD63 (more abundant and widely dispersed than normal). Sequencing of patient DNA detected normal VIPAS39 and apparent homozygosity for a single base pair deletion (c.1531delT, p.Tyr511ThrfsStop10) in exon 20 of VPS33B, predicted to cause a frame shift and premature translation stop codon. Gene sequencing of the parents detected the identical VPS33B mutation in the mother heterozygous to a normal allele; no mutation was found in the father. Array comparative genomic hybridization (aCGH) – which allows detection of deletions and amplification mutations of one or more exons within a given gene – uncovered an approximately 140 kb deletion mutation encompassing the entire VPS33B gene in our patient (g.91,478,004 – proximal to g.91,618.247 – distal), confirming compound heterozygosity. According to the online locus-specific ARC database (https://grenada.lumc.nl/LOVD2/ARC), this is the first association of this mutation combination with ARC syndrome.Unusually for ARC syndrome, bleeding indicative of platelet dysfunction was a major presenting symptom in this patient. While the genetic profile is unusual, the pathological platelet hallmarks of ARC syndrome were present: hypogranular platelets on blood film and absence of α-granules via electron microscopy. We were also able to detect other platelet abnormalities via immunofluorescence microscopy. These observations lead us to suspect that ARC syndrome may represent the most severe class within a possible spectrum of platelet function disorders associated with mutations in VPS33B and/or VIPAS39, a possibility that requires further study. Disclosures:No relevant conflicts of interest to declare.

A 6-week-old Girl with Neonatal Cholestatic Jaundice

A 6-week-old Girl with Neonatal Cholestatic Jaundice

Neonatal Cholestatic Jaundice as the First Symptom of a Mutation in the Hepatocyte Nuclear Factor-1β gene (HNF-1β)

This report describes the phenotype of a novel de novo heterozygous frameshift mutation in the hepatocyte nuclear factor-1β gene (HNF-1β or TCF2) manifest as a neonatal paucity of intrahepatic bile ducts. HNF-1β mutations should be considered in neonates with cholestatic jaundice associated with renal malformation or diabetes mellitus.

Outcome of liver disease in children with Alagille syndrome: a study of 163 patients

BACKGROUND AND AIMSVarious opinions have been expressed as to the long term prognosis of liver disease associated with Alagille syndrome (AGS).PATIENTS AND METHODSWe reviewed the outcome of 163 children with...

North American Indian Cirrhosis in Children: A Review of 30 Cases

ABSTRACTBackgroundNorth American Indian childhood cirrhosis (NAIC) is a distinct, rapidly evolving form of familial cholestasis found in aboriginal children from northwestern Quebec. This is a retrospective review of the 30 patients treated in Quebec since the discovery of NAIC in 1970.MethodsThe clinical records and histologic samples from 30 patients were reviewed. Extensive metabolic, biochemical, viral, genetic, and radiologic studies were performed in most patients.ResultsGenetic analysis suggests autosomal recessive inheritance and a carrier frequency of 10% in this population. Gene mapping studies showed that the NAIC gene is located on chromosome 16q22. Typically, patients have neonatal cholestatic jaundice (70%) or hepatosplenomegaly (20%) with resolution of clinical jaundice by age 1 year but persistent direct hyperbilirubinemia. Portal hypertension was documented in 29 patients (91%). Variceal bleeding (15 patients, 50%) occurred as early as age 10 months. Surgical portosystemic shunting was performed in 13 of these 15 patients (87%); 4 (31%) rebled after 1 to 5 years. Fourteen patients died (47%). In 10 (71%), liver disease was the cause. Four children died of liver failure before liver transplantation became available. In transplanted livers, no recurrence of NAIC was observed after 1 to 10 years. Recognized infectious, metabolic, toxic, autoimmune, and obstructive causes of cirrhosis have been eliminated. The histologic features of NAIC show early bile duct proliferation and rapid development of portal fibrosis and biliary cirrhosis, suggesting a cholangiopathic phenomenon.ConclusionTogether with gene mapping studies showing that the NAIC gene is different from those of other familial cholestases, these observations suggest that NAIC is a distinct entity that could be classified as “progressive familial cholangiopathy.”

Neonatal cholestasis: A new presentation of X-linked adrenoleukodystrophy

A French-Canadian boy presented with neonatal cholestasis and failure to thrive, bilateral polar cataracts, anemia, thrombocytopenia and hypolonia. Bom at 37 weeks gestational age, he weighed 2450 g (10%ile), with length 46 cm (10%ile) and head circumference 33 cm (50%ile). Jaundice was present at birth. No dysmorphism was noted Transaminases were consistently elevated >2-fold. Liver biopsy showed cholestasis and confirmed the presence of calalase-posilive structures, with normal peroxisomes and mitochondria. HIDA scintigraphy showed mild hepatocellular dysfunction. Other investigations including endoscopy, plasma and urine amino acids, serum copper, alpha-1-antitrypsin levels, erythrocyte galactose-1-phosphate levels, karyotype (46, XY) and TORCH viral studies were non-diagnostic. Brainstem auditory evoked potentials showed mild peripheral hearing loss at 3 weeks of age, and a central loss when repeated at 8 months of age. He developed cachexia, progressive hepatomegaly, splenomegaly, osteopenia, bruxism and opisthotonic posturing, with a progressive motor delay. CT scan revealed cortical atrophy. He died of liver failure at age 12 months after frequent episodes of gastrointestinal bleeding and continued neurological deterioration. Post-mortem, plasma very long-chain fatty acids (VLCFAs) results became available, showing elevation of the C26:C22 ratio. Phytanic acid, assayed on three stored samples was normal in two and 3-fold elevated in one. Other peroxisomal function tests including plasma pipecolic acid and rbc plasmalogen ratios were normal, but C18 DMA levels were somewhat lower than normal. Fibroblast C26:0 and C22 levels were elevated 5-fold, and the C26/C22 ratio, 9-fold. Oxidation of C24:0 was 20% of control values. On immunostaining with antibody to the ALD protein, fibroblasts were CRIM negative. The ALD protein gene contained a previously-unreported mutation, a thymine-to-cytosine transition at nucleotide 1654 in exon 7, predicted to change Ser 552 to Pro in the ATP binding domain. Although the patient's mother had normal plasma VLCFA levels, a subsequent pregnancy showed an elevated C26/C22 ratio in amniocytes and was terminated. A similar patient with biochemically-proven ALD and rapidly-progressive cholestasis was recently reported (Corzo. D. et al., Am J Hum Genet 65, 4 (Suppl.): A1295) demonstrating that the association of mutations in the ALD protein gene and neonatal cholestasis is not spurious, and expanding the phenotypic spectrum of ALD to include neonatal cholestatic jaundice with liver failure.

Ocular abnormalities in Alagille syndrome

Objective To assess the type and frequency of ocular abnormalities occurring in Alagille syndrome (AS) in a large group of affected patients and their parents and the potential pathogenetic role of fat-soluble vitamin deficiency. Design Observational case series. Participants Twenty-two children with AS and 23 of their parents participated. Main outcome measures Participants underwent full ophthalmic examination, including refraction, orthoptic examination, keratometry, slit-lamp examination, and funduscopy. Corneal diameter measurement was performed in a subset of nine and fluorescein angiography in a subset of six. Serum levels of vitamins A and E and cholesterol were measured. Results The most common ocular abnormalities in patients with AS were posterior embryotoxon (95%), iris abnormalities (45%), diffuse fundus hypopigmentation (57%, a previously unreported finding), speckling of the retinal pigment epithelium (33%), and optic disc anomalies (76%). Microcornea was not associated with large refractive errors, and visual acuity was not significantly affected by these ocular changes. Vitamin levels were normal. Ocular abnormalities including posterior embryotoxon, iris abnormalities, and optic disc or fundus pigmentary changes were detected in one parent in 36% of cases. Conclusions Alagille syndrome is associated with a characteristic group of ocular findings without apparent serious functional significance and probably unrelated to fat-soluble vitamin deficiency. Simple ophthalmic examination of children with neonatal cholestatic jaundice and their parents should allow early diagnosis of AS, eliminating the need for extensive and invasive investigations.

Sclerosing cholangitis in children

We report on 56 children with sclerosing cholangitis (SC) seen between 1972 and 1992. The first symptoms occurred at a mean age of 3.7 years; 15 infants had neonatal cholestatic jaundice. At diagnosis, cholestatic jaundice was present in 25 children, hepatomegaly in 54, splenomegaly in 41, and ascites in 12. Serum alkaline phosphatase activity was increased in 49 patients and γ-glutamyltransferase activity in all patients tested. Most often the histopathologic findings were extensive portal fibrosis and neoductular proliferation. Cholangiography showed abnormal intrahepatic bile ducts in all children and abnormal extrahepatic bile ducts in 35 (63%). The children were separated into three groups: (1) those with SC of neonatal onset (27%); (2) those with SC of postneonatal onset associated with another disease (55%)—histiocytosis X in 14 children, immunodeficiency syndromes in 8, chronic inflammatory bowel disease or autoimmune hepatitis in 8, and congenital psoriasis in 1; and (3) those with SC of postneonatal onset without an associated disease (18%). Biliary cirrhosis was present in all but three children after 6 months to 19.3 years of follow-up. Eleven children died of portal hypertension or liver failure, and six died of a complication related to the associated disease. Fifteen children had liver transplantation; 11 of these are alive 6 months to 61/2 years later without recurrence of SC. The overall estimated median survival time of children with SC was 10 years from clinical onset. These results indicate that SC should be suspected in all children with a chronic cholestatic disease and increased serum γ-glutamyl transferase activity, especially when diseases known to be associated with SC are present. The prognosis is poor, but liver transplantation should be considered except in those with severe immunodeficiency syndromes. (J P EDIATR 1994;124:49-56)

Liver disease in children with PiZZ alpha 1-antitrypsin deficiency.

We present our experience with 18 pediatric patients with alpha 1-antitrypsin deficiency of the PiZZ phenotype. Fifteen patients (83%) presented with neonatal cholestatic jaundice at a mean age of 2 +/- 0.6 months (+/- S.D.). The male:female ratio was 15:3, indicating a male predominance. All metabolic, infectious and obstructive causes of jaundice were ruled out by appropriate tests in the patients with neonatal cholestasis. Liver biopsy in 14 patients with neonatal cholestasis showed a histological picture of cholestasis in all biopsies; neonatal giant cell hepatitis appeared in seven, increased fibrosis in appeared five and established liver cirrhosis appeared in two biopsies. Patients were followed for a mean of 3.7 +/- 2.4 years (+/- S.D.). Of the 15 patients with neonatal cholestasis, 3 under went liver transplantation because of decompensated liver cirrhosis at 3, 3 1/2 and 7 years. Two patients died at 4 months and 3 years from complications of liver cirrhosis. Of the remaining 10 patients, 3 had histological evidence of liver cirrhosis, and the remaining 7 patients continue to have enlarged liver and spleen with abnormal liver function tests. Of the three patients without history of neonatal cholestasis, only one had enlarged liver and spleen, and the remaining two are healthy with normal liver function tests. Our experience indicates serious liver disease is highly likely to develop in patients with PiZZ alpha 1-antitrypsin deficiency who present with neonatal cholestatic jaundice. Our experience differs from more recent reports on such patients.

α1-Antitrypsin deficiency presenting with ascites and cirrhosis in the neonatal period

We report a 2-wk-old baby with α1-antitrypsin deficiency of Pizz phenotype, who presented with massive ascites and hepatomegaly. Liver biopsy disclosed active established cirrhosis. Unlike all other reported newborns with Pizz type, the patient had no evidence of neonatal cholestatic jaundice. The presentation of Pizz with established liver cirrhosis at such an early age not only adds another cause of cryptogenic cirrhosis in the neonatal period, but also points to a liver insult in some patients with Pizz, which is already determined in utero.

The use of diethyl-IDA Tc 99m clearance curves in the differentiation of biliary atresia from other forms of neonatal jaundice.

A family of isotope elimination curves that reflects changes in the biodistribution of diethyl-IDA Tc 99m in neonatal cholestatic jaundice and biliary atresia is defined. Time/activity curves generated from equal areas over the heart and liver were evaluated separately and in conjunction with the scintigraphic data. Patients without scintigraphic evidence of significant hepatic uptake and with a hepatic curve that resembled the cardiac curve were found to have neonatal hepatitis. Good hepatic uptake and a hepatic curve with a terminal portion that appeared to be parallel to or divergent from the cardiac curve were associated with biliary atresia. Apparently converging hepatic and cardiac curves were associated with biliary patency. Although preliminary, these results provide further documentation that diethyl-IDA Tc 99m is useful in discriminating biliary atresia from other causes of cholestatic jaundice, while reducing radiation exposure and the need for pharmacologic intervention.