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Diana Antunes1; Marcia Rodrigues1; Anaxore Casimiro2; Ana Cristina Ferreira3; Teresa Lourenco1; Teresa Kay1; Luis Nunes1; Silvia Sequeira3

1 - Serviço de Genética, Área Pediatria Médica, Hospital Dona Estefânia, CHLC
2 - Área de Pediatria Médica, Hospital Dona Estefânia, CHLC
3 - Unidade de Doenças Metabólicas, Área Pediatria Médica, Hospital Dona Estefânia, CHLC

- Poster no XI Simpósio Internacional da Sociedade Portuguesa de Doenças Metabólicas,  Porto, 19 a 20 de Março de 2015

Introduction: The etiology of neonatal cholestasis is rather complex and includes infectious, structural, toxic, vascular, immune, metabolic and/or genetic disorders. A careful history and physical examination can therefore be very helpful in the differential diagnosis of some cases. Arthrogryposis, Renal tubular dysfunction and Cholestasis (ARC) syndrome (OMIM #208085) is a very rare autosomal recessive multisystem disorder usually caused by mutations in the VPS33B or VIPAR genes.
Case report: We describe a female newborn, second child from consanguineous Pakistani parents, with cholestatic jaundice She was born at 40 weeks from caesarean section after an uneventful pregnancy with adequate somatometry. Besides jaundice she also presented severe failure to thrive, dysmorphic features, hirsutism, dry and scaly skin, congenital hip dysplasia, limited extension of lower limbs and bilateral club-feet. Laboratory investigations disclosed high direct bilirubin with normal GT and progressive proteinuria and glycosuria together with low serum levels of bicarbonate, phosphorus and potassium, compatible with a Fanconi syndrome. ARC syndrome was suspected and sequence analysis of exon 3 of the VPS33B gene identified a homozygous G to C base substitution at nucleotide position 178-1 (c.178-1G>C) an invariant base within the slice acceptor site of inton2/exon 3 boundary. Both parents were heterozygous carriers of the same mutation. The child deceased shortly after she completed three months due to sepsis. The mother is currently in her sixth pregnancy. She had three subsequent pregnancies one ending in a spontaneous abortion and two in which prenatal diagnosis was offered and revealed foetus with homozygosity for the same mutation. Parents decided to terminate pregnancy in both cases.
Discussion: Genetic diagnosis in this case allows proper information and counselling of the parents and family of a child diagnosed with ARC syndrome. The diagnosis of a possible ARC syndrome should be kept in mind in infants with cholestatic jaundice, especially if they are of a Pakistani or Saudi Arabian origin due to a high prevalence in these populations.

Palavras Chave: arthrogryposis, renal tubular dysfunction, cholestasis, ARC syndrome