Aagenaes syndrome

Synonyms

6

Overview

Aagenaes syndrome: A rare inherited birth abnormality involving underdeveloped lymph vessels which results in swollen legs and liver problems.

A syndrome characterised by congenital hypoplasia of lymph vessels, which causes lymphedema of the legs and recurrent cholestasis in infancy, and slow progress to hepatic cirrhosis and giant-cell hepatitis with fibrosis of the portal tracts1. The genetic cause is unknown, but it is autosomal recessively inherited and the gene is located to chromosome 15q1,2. A common feature of the condition is a generalised lymphatic anomaly, which may be indicative of the defect being lymphangiogenetic in origin1. The condition is particularly frequent in southern Norway, where more than half the cases are reported from, but is found in patients in other parts of Europe and the U.S.2. It is named after Oystein Aagenaes, a Norwegian paediatrician.

Symptoms

  • Underdeveloped lymph vessels
  • Lymphedema of the legs
  • Swollen legs
  • Infant cholestasis
  • Liver scarring
  • Abdominal pain
  • Abnormality of lipid metabolism
  • Abnormality of urine homeostasis
  • Biliary tract abnormality

Causes

Bull et al. (2000) performed a genome screen, using DNA from 8 Norwegian patients with cholestasis-lymphedema syndrome and from 7 unaffected relatives, all from an extended pedigree. Regions potentially shared identical by descent in patients were further characterized in a larger set of Norwegian patients. The patients manifested extensive allele and haplotype sharing over a 6.6-cM region on chromosome 15 between markers D15S979 and D15S652.

Prognosis

Drivdal et al. (2006) stated that 40 Norwegian patients have been known to have cholestasis-lymphedema syndrome, of whom 25 were still alive at the date of the report. Nine died in infancy or early childhood, mainly of bleeding before vitamin K treatment was available; 4 died of cirrhosis at ages 2, 7, 8, and 50 years, respectively; and 2 died of unrelated causes in late adulthood. Of those patients still living, 3 underwent liver transplantation in infancy, and 2 had slow progression to cirrhosis. Analysis of 15 Norwegian patients over age 10 years with the disorder but without signs or symptoms of cholestasis showed significantly increased serum transaminase levels compared to controls, and albumin was decreased in older patients. Lymphedema ranged from moderate to massive. Retrospectively, it appeared that those with remission of liver disease by about 2 to 2.5 years of age showed a better prognosis. Drivdal et al. (2006) concluded that more than 50% of patients with Norwegian cholestasis-lymphedema syndrome can expect a normal life span given proper nutritional and vitamin treatment and that most patients have a relatively good prognosis compared to patients with other types of hereditary neonatal cholestasis.

Resources

  • NIH