Liver and Cardiac Involvement in Shwachman-Diamond Syndrome: A Literature Review

Abstract

Shwachman-Diamond syndrome (SDS) is an autosomal recessive inherited disease of the SBDS gene. It has multi-organ involvement but primarily affects the bone marrow and the pancreas. This disease is more commonly found in males than females, and its earliest manifestation in infancy is pancytopenia, most especially neutropenia. Our article attempts an in-depth analysis of the hepatic and cardiac association in this disease and the severity of this association. For the purpose of this study, we engaged in an in-depth research of critically appraised literature and published articles. We searched for such articles on PubMed and Google Scholar using regular and Medical Subject Headings (MeSH) keywords. We eventually selected 32 articles from the search results and carefully read through and analyzed them. These articles showed the usual age of diagnosis of SDS to be at infancy (before age one), with a predominantly median survival age of 35 years. All the published articles we reviewed showed some hepatic and cardiac associations with SDS, but the extent of the associations varied. Even though most hepatic involvements were found to be benign, some severe cases led to fibrosis and hepatic failure. Although there is no particular consensus as to the exact outcome of cardiac involvement, the few cases we reviewed showed that cardiac association could be a severe complication and could even be fatal. Most of the cases reported in the literature had been diagnosed at autopsy.

Hepatic ribosomal protein S6 (Rps6) insufficiency results in failed bile duct development and loss of hepatocyte viability; a ribosomopathy-like phenotype that is partially p53-dependent

“…Our results suggest that future investigations into the role of RiBi in mammalian hepatobiliary development and disease are warranted. Although NAIC currently stands as the only ribosomopathy known to affect the liver, a subset of SDS patients present with persistent cholestasis, biliary hamartomas or other indicators of hepatic disease [159][160][161]. Moreover, Sbds-deficiency not only induces atrophy of the pancreas, but also of the liver [139], suggesting that the liver may be more vulnerable in some of the ribosomopathies than previously appreciated.…”

An Unusual Presentation of Extremely Early Neonatal Cirrhosis in Shwachman-Diamond Syndrome: A Case Report

“…It more commonly affects males, with the age of presentation being infancy. The earliest manifestation in infancy is pancytopenia, especially neutropenia [ 6 ]. The classic presentation of SDS in infancy or early childhood is failure to thrive, growth retardation, steatorrhoea, recurrent infections, bone marrow failure and aplastic anaemia [ 7 ].…”

“…This is usually transient and resolves over time [ 4 ]. SDS with abnormal transaminase levels was detected in neonates, and these returned to normal with increasing age [ 6 ]. However, in our case, the severity of hepatic involvement in a neonate to the extent of cirrhosis and liver failure is very unusual.…”

“…However, in our case, the severity of hepatic involvement in a neonate to the extent of cirrhosis and liver failure is very unusual. Hepatic involvement in SDS is most commonly associated with pancreatic dysfunction in the form of steatorrhoea, malnutrition and failure to thrive, along with a universal finding of haematological abnormality [ 6 , 10 ].…”

Two mutations in theSBDSgene reveal a diagnosis of Shwachman–Diamond syndrome in a patient with atypical symptoms

“…Evidence has shown the association of liver disease with this phenotype, although rarely. This involvement can include different levels of liver manifestations, such as different forms of persistent chronic liver disease due to hepatic fibrosis, including, in some cases, cirrhosis (Liebman et al 1979;Toiviainen-Salo et al 2009;Richards et al 2015;Camacho et al 2019;Lawal et al 2020). Abnormal transaminase levels were often detected in neonates, and these returned to normal with age.…”