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Progressive hyperpigmentation in a Taiwanese child due to an inborn error of vitamin B12 metabolism (cblJ)
Author(s) -
Takeichi T.,
Hsu C.K.,
Yang H.S.,
Chen H.Y.,
Wong T.W.,
Tsai W.L.,
Chao S.C.,
Lee J.Y.Y.,
Akiyama M.,
Simpson M.A.,
McGrath J.A.
Publication year - 2015
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.13413
Subject(s) - cobalamin , hyperpigmentation , skin hyperpigmentation , organomegaly , hypopigmentation , medicine , melanocyte , melanosome , biology , endocrinology , dermatology , vitamin b12 , genetics , melanin , cancer research , melanoma , disease
Summary The physiology of human skin pigmentation is varied and complex, with an extensive melanogenic paracrine network involving mesenchymal and epithelial cells, contributing to the regulation of melanocyte survival and proliferation and melanogenesis. Mutations in several genes, involving predominantly the KIT ligand/c‐Kit and Ras/mitogen‐activated protein kinase signalling pathways, have been implicated in a spectrum of diseases in which there is hyperpigmentation, hypopigmentation or both. Here, we report on a 12‐year‐old girl from Taiwan with a 6‐year history of diffuse progressive skin hyperpigmentation resulting from a different aetiology: an inborn metabolic disorder of vitamin B12 (cobalamin), designated cblJ. Using whole‐exome sequencing we identified a homozygous mutation in ABCD 4 (c.423C>G; p.Asn141Lys), which encodes an ATP ‐binding cassette transporter with a role in the intracellular processing of cobalamin. The patient had biochemical and haematological evidence of cobalamin deficiency but no other clinical abnormalities apart from a slight lightening of her previously black hair. Of note, she had no neurological symptoms or signs. Treatment with oral cobalamin (3 mg daily) led to metabolic correction and some reduction in the skin hyperpigmentation at the 3‐month follow‐up. This case demonstrates that defects or deficiencies of cobalamin should be remembered in the differential diagnosis of diffuse hyperpigmentary skin disorders.