Pyrimidine-5'-nucleotidase Campinas, a new mutation (p.R56G) in the NT5C3 gene associated with pyrimidine-5'-nucleotidase type I deficiency and influence of Gilbert's Syndrome on clinical expression.

Pyrimidine-5'-nucleotidase type I (P5'NI) deficiency is an autosomal recessive condition that causes nonspherocytic hemolytic anemia, characterized by marked basophilic stippling and pyrimidine nucleotide accumulation in erythrocytes. We herein present two African descendant patients, father and daughter, with P5'N deficiency, both born from first cousins. Investigation of the promoter polymorphism of the uridine diphospho glucuronosyl transferase 1A (UGT1A) gene revealed that the father was homozygous for the allele (TA7) and the daughter heterozygous (TA6/TA7). P5'NI gene (NT5C3) gene sequencing revealed a further change in homozygosity at amino acid position 56 (p.R56G), located in a highly conserved region. Both patients developed gallstones; however the father, who had undergone surgery for the removal of stones, had extremely severe intrahepatic cholestasis and, liver biopsy revealed fibrosis and siderosis grade III, leading us to believe that the homozygosity of the UGT1A polymorphism was responsible for the more severe clinical features in the father. Moreover, our results show how the clinical expression of hemolytic anemia is influenced by epistatic factors and we describe a new mutation in the P5'N gene associated with enzyme deficiency, iron overload, and severe gallstone formation. To our knowledge, this is the first description of P5'N deficiency in South Americans.

Trastornos delirante somatomorfo corporal asociado a enfermedad de Gilbert / Corporal somatomorphic delirious disorder associated to Gilbert's disease

El caso en cuestión tiene como importancia que se asocia por primera vez la presencia de un trastorno delirante tipo somático (dismorfofobia corporal) a una afección llamada enfermedad de Gilbert (hiperbilirrubinemia congénita o adquirida), que se caracteriza por un déficit congénito de la enzima glucoronil-transferasa que conjuga la bilirrubina indirecta en directa a nivel hepático, por lo tanto dicho déficit aumenta los niveles en sangre de la bilirrubina indirecta, lo que provoca la aparición de un discreto tinte subictérico en la piel y mucosas. Cuando este déficit enzimático es congénito se llama enfermedad de Gilbert y cuando es posterior a un daño hepático, por ejemplo, hepatitis viral tipo A, entonces se llama síndrome de Gilbert.

This case is relevant because for the first time a somatic delirious disorder (corporal dismorphophobia) is associated to Gilbert’s disease (congenital or acquired hyperbilirrubinemia), which is characterized by a congenital deficit of glucoronil – transferase enzyme that conjugates indirect bilirrubine in direct bilirrubine at hepatic level, due to this, such a deficit increases the indirect bilirrubine blood levels and this produces a mild subicteric color on the skin and mucosa. When this enzymatic deficit is congenital it is called Gilbert’s disease, and when it happens after hepatic damages, for instance viral hepatitis type A, it is called Gilbert’s syndrome.

[Electron microscopy of the liver in Gilbert's syndrome]. / Microscopia electrônica do fígado na síndrome de Gilbert.

Hepatic biopsy of five patients with Gilbert's syndrome was examined at the electron microscopy and only one disclosed incharacteristic alterations. The others were considered normal.