Benign disease characterized by familial idiopathic
jaundice presenting with chronic intermittent conjugated hyperbilirubinemia.
Dubin-Johnson-Sprinz Nelson Syndrome.
Occurs in both sexes (although males are affected about
1.5 times more often than females) and in all nationalities and races. The
highest prevalence in the general population (1:1300) is found in Iranian
Autosomal recessive, with a reduced penetrance
in females. The gene encoding for the human canalicular multispecific
organic anion transporter (cMOAT) protein has been mapped to 10q24.
The cMOAT protein is involved in the
energy-dependent transport of certain bilirubin glucuronides and organic
acids (except bile acids) against a concentration gradient across the
canalicular membrane of the hepatocyte. The cMOAT protein defect in
Dubin-Johnson syndrome (DJS) leads to decreased hepatobiliary transport and
seems to be responsible for the predominantly conjugated hyperbilirubinemia
and the intralysosomal accumulation of pigment in hepatocytes.
In healthy people, the total daily biliary
coproporphyrinogen (CPG) excretion (a by-product of the heme synthesis) is
about three times higher than urinary CPG excretion, and urinary CPG III
concentration is about three times higher than CPG I concentration. In DJS,
the total amount of urinary CPG is normal, but CPG isomer I accounts for
80% of total CPG. Hence, the diagnosis is based on increased levels of
CPG I in the urine, whereas the CPG III level is below normal. Furthermore,
the rise in the sulfobromophthalein sodium test is delayed, and the liver
appears macroscopically dark blue or even black. Histologically, the
cytoplasm of hepatocytes (especially in zone III) contains big lysosomes
packed with a lipochromic pigment, which is responsible for the brown-black
color. This pigment has many similarities to melanin but is not melanin. It
has been theorized that the pigment may be composed of polymers of
epinephrine metabolites. The amount of pigment is variable; for example, it
can disappear almost completely during an acute viral hepatitis but then
reappear slowly after recovery.
Main findings of the disease are hepatomegaly
associated with abdominal pain and jaundice. Although cases in neonates have
been described, onset usually is in early adulthood, presenting with a
nonpruritic jaundice that is caused by increased conjugated
hyperbilirubinemia. Liver function is otherwise normal. However, in up to
two thirds of DJS patients (especially those of Iranian Jewish descent), a
prolonged prothrombin time secondary to reduced activity of factor VII has
Ensure the liver anomalies truly
result from DJS and that no other intercurrent disease is causing the liver
dysfunction. Ask about prolonged bleeding; if in doubt or before major
surgery, check for coagulation disorder.
If blood loss is significant, check
coagulation and treat accordingly.
Jaundice may transiently increase
postoperatively. Consequently, it seems prudent to avoid halothane to
prevent its implication in the development of postoperative jaundice.
Pregnancy, exogenous administration of hormones (e.g., oral contraceptives),
and stress can trigger or exacerbate an existing jaundice. Factor VII ...