50 Years Ago in The Journal of Pediatrics:
Infantile Cirrhosis of the Liver (Sen's Syndrome) with Particular Reference to the Sulphur-Containing Amino Acids
Article Outline
Chaudhuri, A. J Pediatr 1960;57:230-47.
The mystery began in 1887 when Sen first described an entity of infantile cirrhosis in eastern India. Subsequent clinical reports depicted a toddler with insidious malaise, low-grade fever, and then the onset of hepatomegaly, development of portal hypertension, jaundice, and eventually death. In 1960 Chaudhari et al presented 5 Indian children with cirrhosis and characterized them on the basis of histopathologic and biochemical investigations. They divided their cohort into 2 groups on the basis of differential gamma globulin fractions. They then characterized in detail their biochemical profiles and found that phenylalanine, tyrosine, and proline were higher in children with cirrhosis compared with normal subjects and that urinary cysteine levels differentiated between the 2 groups. The report suggested that this condition may actually be a syndrome made up of more than 2 entities.
Subsequent studies of Indian childhood cirrhosis did not pursue this biochemical profiling. Instead, the description of the histopathologic study, namely hepatocyte necrosis, deposition of Mallory's hyaline, marked fibrosis, and massive copper deposition, focused much of the debate in the last 50 years on the link with dietary copper. It was widely held that copper contamination of milk from brass utensils used in rural India on a genetically susceptible background was associated with the development of Indian childhood cirrhosis, and it was considered an ecogenetic disorder.
However, most recently a multicenter consortium in India attempted to resolve some of the dilemmas surrounding Indian childhood cirrhosis. The feeding practices and histopathologic study from 748 cases did not support the role of dietary copper in this condition, but another cause was not evident.1
Thus, after 50 years the mystery ensues, and the cause of Indian childhood cirrhosis remains elusive. This is disappointing because several other rare pediatric liver diseases such as North American Indian childhood cirrhosis have been elegantly defined and their genetic basis elucidated.2 It is possible, as Chaudhari suggested, that Indian childhood cirrhosis is more than 1 entity and actually the common end result of multiple different causes. Because, for unknown reasons, this condition has now become exceptionally rare, perhaps the window of opportunity that once existed to fully understand this curious disease has now closed.
References
- Sriramachari, S. Indian Childhood Cirrhosis: A Multicentric National Collaborative Study. 2006. Available at http://www.icmr.nic.in. Accessed February 24, 2010.
- A missense mutation (R565W) in cirrhin (FLJ14728) in North American Indian childhood cirrhosis. Am J Hum Genet. 2002;71:1443–1449
PII: S0022-3476(10)00193-9
doi:10.1016/j.jpeds.2010.02.049
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