CASE REPORT


https://doi.org/10.5005/jp-journals-11009-0151
Annals of Pediatric Gastroenterology and Hepatology ISPGHAN
Volume 6 | Issue 1 | Year 2024

A Rare Cause of Neonatal Liver Failure


Snigdha Singh1, Aathira Ravindranath2, Rajkumar P Wadhwa3, Benaganahalli S Sandeep4, Kalavathi L Narendra5

1Department of Gastroenterology, BGS Apollo Hospital, Bengaluru, Karnataka, India

2Department of Pediatric Gastroenterology, Apollo Hospital, Mysore, Karnataka, India

3Department of Gastroenterology, Apollo Hospital, Mysore, Karnataka, India

4Department of Radiology, Apollo Hospital, Mysore, Karnataka, India

5Department of Pathology, Apollo Hospital, Mysore, Karnataka, India

Corresponding Author: Aathira Ravindranath, Department of Pediatric Gastroenterology, Apollo Hospital, Mysore, Karnataka, India, Phone: +91 8527710993, e-mail: aathira.r@gmail.com

Received: 01 November 2023; Accepted: 21 February 2024; Published on: 10 April 2024

ABSTRACT

A 1-month-old infant presented with complaints of jaundice and poor oral intake for 14 days. Liver function tests were significantly deranged, and the prothrombin time-international normalized ratio (PT-INR) was high. Ultrasonography showed hepatomegaly with periportal cuffing and massive splenomegaly suggestive of an infiltrative disorder. Bone marrow aspiration and biopsy showed lipid-laden macrophages, which helped in making a diagnosis of Niemann–Pick disease. Whole exome sequencing results further confirmed the diagnosis of Niemann–Pick disease type C (NPC). NPC is a rare cause of neonatal liver failure, and since there is no known treatment for the illness, investigations must be specifically tailored to produce a diagnosis in time, which can aid in the management and prenatal counseling.

How to cite this article: Singh S, Ravindranath A, Wadhwa RP, et al. A Rare Cause of Neonatal Liver Failure. Ann Pediatr Gastroenterol Hepatol 2024;6(1):1–2.

Source of support: Nil

Conflict of interest: Dr Aathira ravindranath is associated as the Editorial Board member of this journal and this manuscript was subjected to this journal’s standard review procedures, with this peer review handled independently of this editorial board member and his research group.

Keywords: Case report, Liver failure, Liver transplantation, Niemann–Pick type C, Neonate, Storage disorder

A 1-month-old baby who was exclusively breastfed and born to consanguineously married parents presented with a history of jaundice for 14 days and poor feeding for 5 days. On examination, the baby was deeply icteric lethargic; the abdomen was distended with prominent veins, hepatomegaly (4 cm below costal margin), splenomegaly (8 cm below costal margin) and shifting dullness. Investigations showed—total bilirubin 27 mg/dL, direct bilirubin 20 mg/dL, alanine aminotransferase 55 IU/L, aspartate aminotransferase 148 IU/L, alkaline phosphatase 445 IU/L, γ-glutamyl transpeptidase 222 IU/L, prothrombin time-international normalized ratio (PT-INR) 8.5, hemoglobin 9.9 gm/dL, total leukocyte count 6700/cumm (neutrophils 61%, leukocytes 30%, monocytes 9%), platelets 171,000/cumm, serum sodium 128 mEq/L, serum potassium 4 mEq/L, and blood lactate 2.48 mmol/L. Renal functions were normal. Abdominal ultrasonogram showed hepatomegaly with periportal cuffing (Fig. 1), massive splenomegaly and ascites. Fundus examination was normal. Galactosemia, tyrosinemia, neonatal hemochromatosis and herpes simplex infection were excluded with appropriate investigations. Massive splenomegaly was suggestive of infiltrative disorder. For ascertaining the etiology of liver failure, bone marrow aspiration and biopsy were done, which showed lipid-laden foamy macrophages suggestive of Niemann–Pick disease (Figs 234). Clinical exome sequencing was performed after parental consent, which revealed homozygous single base pair duplication in exon 4 of Niemann–Pick disease type C1 (NPC1) gene (chr18:g.23568853_23568854insT; Depth:86x) [pathogenic] that resulted in a frameshift and premature truncation of the protein 25 amino acids downstream to codon 145 (p.Gln145ThrfsTer25; ENST00000269228.10), thus confirming NPC.1 The baby succumbed to progressive liver failure after 12 days.

Fig. 1: Ultrasonogram showing periportal cuffing

Fig. 2: Bone marrow aspiration showing lipid-laden macrophage

Fig. 3: Bone marrow aspiration showing lipid-laden macrophage with a foamy appearance

Fig. 4: Bone marrow biopsy showing infiltration by multiple lipid-laden macrophages (arrows)

DISCUSSION

Niemann–Pick disease type C (NPC) is an autosomal recessive disorder that results from biallelic mutations in NPC1 or NPC2 genes, which cause the accumulation of unesterified cholesterol in the lysosomes. The incidence of NPC is 1 in 100,000.2 The clinical spectrum, severity, and pattern of organ involvement are heterogeneous. Visceral involvement predominates in infancy and neurodegenerative manifestations in childhood. Affected adults present with neuropsychiatric manifestations. In the majority of infants, cholestatic jaundice resolves by 6 months of age, but organomegaly persists, and neurological symptoms like hypotonia, gaze palsy, and developmental delay develop later. However, <5% will develop neonatal liver failure.3 Among all infants with acute liver failure, NPC accounts for <2%.4 Diagnosing NPC in the setting of neonatal liver failure is difficult due to the absence of reliable blood markers. Massive splenomegaly is an important clue to an underlying infiltrative disorder that can cause neonatal liver failure, which includes hemophagocytic lymphohistiocytosis, neonatal leukemia and Gaucher’s disease apart from NPC. The yield of bone marrow examination in detecting storage cells is 64%.5 Filipin staining of cultured fibroblasts will demonstrate the intracellular unesterified cholesterol crystals. Confirmation of genetic mutation by exome sequencing will aid in prognostication and also in antenatal screening for subsequent pregnancies. The prognosis is poor for those who present with neonatal liver failure. Even though liver transplantation (LT) can provide temporary improvement, these babies develop neurological manifestations later. Establishing a definitive diagnosis is imperative before offering LT, as rapid neurological worsening will overshadow the benefits achieved by LT. In many cases, diagnosis of NPC was confirmed after LT, and these children developed progressive neurological deterioration later despite starting miglustat.6 Miglustat is an inhibitor of glycosylceramide synthase enzyme, and it could stall the progression of neurological symptoms.7 Robust evidence is lacking to assess if LT can be offered for neonatal liver failure along with early administration of miglustat that could stabilize the neurological manifestations.

ORCID

Snigdha Singh https://orcid.org/0009-0006-0081-759X

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