Pyoderma Gangrenosum Associated with Sclerosing Cholangitis, Type 1 Diabetes Mellitus and Ulcerative Colitis

We describe the case of a 22-year-old black female with type 1 diabetes mellitus diagnosed when she was 12 years old. She first presented (March 1994) with pustules and ulcerations on the upper and lower limbs, trunk and scalp at the age 17. The diagnosis of pyoderma gangrenosum was made. Since presentation, changes in liver function were detected and subsequent study led to the diagnosis of sclerosing cholangitis. The diagnosis of ulcerative colitis was made after colonoscopy. Partial response was obtained with minocycline and clofazimine, but treatment with 5-aminosalicylic acid achieved no improvement of the ulcerations. Liver transplantation, followed by immunosuppressive therapy led to complete regression of the cutaneous lesions.

Panencefalite Esclerosante Subaguda

A panencefalite esclerosante subaguda é um doença neurodegenerativa lentamente progressiva da infância e adolescência, caracterizada por demência, ataxia, mioclonias e outros sinais neurológicos focais, com desfecho fatal invariável. a autora faz uma revisão do tema, incidindo nos aspectos epidemiológicos, na expressão da doença, nos aspectos conhecidos sobre o comportamento do agente etiológico - o vírus do sarampo - e sobre a resposta imune do hospedeiro, profilaxia do sarampo e propostas terapêuticas.

A Novel Autosomal Recessive GJA1 Missense Mutation Linked to Craniometaphyseal Dysplasia

Craniometaphyseal dysplasia (CMD) is a rare sclerosing skeletal disorder with progressive hyperostosis of craniofacial bones. CMD can be inherited in an autosomal dominant (AD) trait or occur after de novo mutations in the pyrophosphate transporter ANKH. Although the autosomal recessive (AR)form of CMD had been mapped to 6q21-22 the mutation has been elusive. In this study, we performed whole-exome sequencing for one subject with AR CMD and identified a novel missense mutation (c.716G>A, p.Arg239Gln) in the C-terminus of the gap junction protein alpha-1 (GJA1) coding for connexin 43 (Cx43). We confirmed this mutation in 6 individuals from 3 additional families. The homozygous mutation cosegregated only with affected family members. Connexin 43 is a major component of gap junctions in osteoblasts, osteocytes, osteoclasts and chondrocytes. Gap junctions are responsible for the diffusion of low molecular weight molecules between cells. Mutations in Cx43 cause several dominant and recessive disorders involving developmental abnormalities of bone such as dominant and recessive oculodentodigital dysplasia (ODDD; MIM #164200, 257850) and isolated syndactyly type III (MIM #186100), the characteristic digital anomaly in ODDD. However, characteristic ocular and dental features of ODDD as well as syndactyly are absent in patients with the recessive Arg239Gln Cx43 mutation. Bone remodeling mechanisms disrupted by this novel Cx43 mutation remain to be elucidated.