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SYNDROME
Disusun oleh:
Muhammad Shiddiq
DEFINISI
Alagille syndrome is a multisystem autosomal
dominant disorder due to defects in the notch signalling
pathway, and can affect the liver, heart, skeleton, eyes,
kidneys, and central nervous system, and there may be
characteristic facial features
Clinical Finding
Frequency (% of Individuals)
Emerick et al [1999]
69/81 (85%)
Subramaniam et al [2
011]
77/103 (75%)
Chronic cholestasis
88/92 (96%)
104/117 (89%)
Cardiac murmur
90/92 (97%)
107/117 (91%)
Eye findings
65/83 (78%)
72/117 (61%) 1
Vertebral anomalies
37/71 (51%)
44/117 (39%) 2
Characteristic facies
86/92 (96%)
91/117 (77%)
Renal disease
28/69 (40%)
27/117 (23%)
Pancreatic
insufficiency
7/17 (41%)
NR
Growth retardation
27/31 (87%)
NR
Intellectual disability
2/92 (2%)
NR
Developmental delay
15/92 (16%)
NR
Spinner N, Leonard LD, Krantz ID. Alagille Syndrome GeneReviews [Internet] 2013.
LIVER DISEASE
Chronic cholestasis occurs in a very high proportion
(95%) of cases, and most commonly, presents in the
neonatal period or first 3 months of life, with jaundice
due to conjugated hyperbilirubinaemia.
Serum bile acids and liver function tests are raised,
pruritus and growth failure may occur, and xanthomas
may be present.
Progressive liver disease, eventually causing cirrhosis
and failure, and requiring liver transplantation, occurs
in approximately 15% of cases
European Journal of Human Genetics (2012) 20, 251257
DIAGNOSIS KLINIS
The histologic finding of bile duct paucity (an
increased portal tract-to-bile duct ratio) on liver biopsy.
In the newborn, a normal ratio of portal tracts to bile
ducts, bile duct proliferation, or a picture suggestive of
neonatal hepatitis may be observed. Overall, bile duct
paucity is present in about 90% of individuals
Spinner N, Leonard LD, Krantz ID. Alagille Syndrome GeneReviews [Internet] 2013.
DIAGNOSIS KLINIS
3 dari 5 gejala mayor berikut:
o Cholestasis
o Cardiac defect (most commonly stenosis of the
peripheral pulmonary artery and its branches)
o Skeletal abnormalities (most commonly butterfly
vertebrae identified in AP chest radiographs)
o Ophthalmologic abnormalities (most commonly
posterior embryotoxon)
o Characteristic facial features
Spinner N, Leonard LD, Krantz ID. Alagille Syndrome GeneReviews [Internet] 2013.
PEMERIKSAAN
Liver
function
tests
(the
conjugated
hyperbilirubinaemia of ALGS is associated with high
GGT levels), serum cholesterol and triglycerides, bile
acids, clotting studies, liver ultrasound, scintiscan, and
biopsy;
Detailed cardiac assessment;
AP spinal X-ray;
Ophthalmic assessment;
Renal ultrasound and renal function tests.
TERIMA KASIH