Congenital hemophagocytic lymphohistiocytosis presenting as neonatal liver failure

Autor: Nicole Graf, Nick Evans
Rok vydání: 2014
Předmět:
Zdroj: Pathology. 46:S33-S34
ISSN: 0031-3025
DOI: 10.1097/01.pat.0000454200.37323.65
Popis: Hemophagocytic lymphohistiocytosis (HLH) is a disorder of immune regulation resulting in unregulated activation of T lymphocytes and macrophages, characterised by proliferation of benign appearing histiocytes with evidence of phagocytosis of hemopoietic cells. HLH may be primary / familial, or secondary. Primary HLH is most commonly autosomal recessive, and presents early in life, usually in the first 2 years. Diagnostic criteria were revised as part of the HLH-2004 clinical trial, and remains a syndrome defined by a unique pattern of clinical findings characterized by severe pathological immune activation. We present a case of congenital HLH, with hydrops fetalis and neonatal hepatic failure. A male infant was delivered at 34 weeks gestation to a non-consanguineous couple. There was severe anemia and thrombocytopenia at birth, associated with a distended abdomen and hepatosplenomegaly. There was a progressive rise in bilirubin and development of hepatic failure with very high ferritin over the following days, with subsequent onset of seizures with hypoxic-ischaemic brain injury, and death on day 4. Postmortem examination confirmed a phenotypically normal male with evidence of hydrops and noted hepatomegaly (181.3 g), striking splenomegaly (73.5 g) and retroperitoneal lymphadenopathy. Histology identified prominent histiocytes displaying hemophagocytosis, most readily identified in the peripancreatic nodes, but also seen in the spleen. There was patchy hepatic necrosis and portal inflammation, with only very subtle sinusoidal hemophagocytic activity. A number of genetic mutations have been described in association with primary HLH, with the most common genes involved being Perforin (PRF1, the first identified gene), Munc 13–4, Munc 18-2 (Syntaxin binding protein 2), and Syntaxin (STX 11), as well as the more recently identified and X-liked gene, XLP2. However, in approximately 40% of cases there is still no identifiable genetic abnormality. This child was confirmed as a compound heterozygote for two different mutations of the PRF-1 gene.
Databáze: OpenAIRE
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