Inheritance of the Dubin-Johnson Syndrome

Urinary total, isomer I, and isomer III coproporphyrin excretion was determined in 16 patients with the Dubin-Johnson syndrome, 73 phenotypically normal family members, and 20 unrelated normal controls of similar age. Normal subjects excreted 24.8 ± 1.3 per cent (mean ± S.E.M.) of urinary coproporphyrin as coproporphyrin I. Patients with the syndrome excreted 88.9 ± 1.3 per cent (mean ± S.E.M.) as coproporphyrin I (p less than 0.001). Twenty-five phenotypically normal parents and children of patients with the syndrome excreted 31.6 ± 1.2 per cent (mean ± S.E.M.) as coproporphyrin I, a value intermediate between results in patients and normal subjects (p less than 0.001). In 48 phenotypically normal more distant relatives, the percentage excretion of coproporphyrin I was distributed over a wide range. These results indicate that, with respect to urinary coproporphyrin excretion, the Dubin-Johnson syndrome is inherited as an autosomal recessive characteristic. THE Dubin-Johnson syndrome is characterized by a black liver and chronic nonhemolytic, predominantly conjugated, hyperbilirubinemia.^{1 2 3 4} Its familial nature has been described^{3 4 5 6 7 8 9 10 11 12 13}; however, previous attempts to detect carriers of the syndrome have been unsuccessful. Normal serum bilirubin concentration, sulfobromophthalein retention (Mandema test),^{13 14 15} sulfobromophthalein relative storage capacity and transport maximum,³¹⁶¹⁷ and absence of hepatic pigmentation have been observed in phenotypically normal but genetically identified obligate carriers.⁹¹⁰ In the absence of a means of identifying carriers of the syndrome, its mode of inheritance remains uncertain. Koskelo et al.¹⁸ discovered, and Ben-Ezzer and her co-workers¹⁹ confirmed, that urinary coproporphyrin I excretion is increased.