Severe Hemolytic Jaundice in a Neonate with a Novel COL4A1 Mutation

Abstract

We report our experience with a preterm infant with severe hemolytic jaundice who required exchange transfusion just after birth. The patient was negative for alloimmune hemolysis as a result of maternal-fetal blood type incompatibility, and tests for inherited defects in erythrocyte metabolism, membrane function, and hemoglobin synthesis were normal. We also performed a bone marrow examination, but could not identify the cause of hemolysis. The patient had several other complications, including porencephaly, epilepsy, elevated serum levels of creatine kinase, and persistent microscopic hematuria. Later, we detected a genetic mutation in COL4A1, which was recently found to be associated with hemolytic anemia. We therefore believe that all of the patient's clinical features, including hemolytic anemia, were due to the mutation in COL4A1. Genetic testing for COL4A1 mutations is recommended in neonates who exhibit hemolytic disease of unknown etiology, especially when other complications compatible with COL4A1-related disorders are present.

ER stress and basement membrane defects combine to cause glomerular and tubular renal disease resulting from Col4a1 mutations in mice

“…Col4a1 mutant mice display reduced blood volume and haematocrit levels but normal plasma volume ( Van Agtmael et al, 2010 ), and recently, anaemia has been described in individuals with a COL4A1 mutation ( Tomotaki et al, 2014 ; Yoneda et al, 2013 ). The mechanism underlying the reduced red blood cell number remained unexplored, but a defect in erythropoiesis or erythrocyte maturation could be a contributing factor whereby the kidney disease affects renal erythropoietin production.…”

MicroRNA-214-5p/TGF-β/Smad2 signaling alters adipogenic differentiation of bone marrow stem cells in postmenopausal osteoporosis

“…Previous studies illustrated that COL4A1 gene mutations were associated with cerebral hemorrhage, microaneurysm, ocular phenotype and kidney diseases of newborns and adults ( 22 , 35 ). A number of studies have investigated the COL4A1 gene as a potential candidate gene of osteoporosis ( 22 , 35 ). The COL4A1 gene can transform from an acyl amino acid to histidine ( 35 ).…”

“…Mutations in the collagen type IV α1 chain (COL4A1), a major component of the basilar membrane, have been implicated in various diseases including HANAC syndrome, renal disease, porencephaly, and cataracts ( 20 , 21 ). From 2005, the occurrence of the COL4A1 gene mutation and associated hereditary disease has started to attract the attention ( 22 , 23 ). The COL4A1 gene is the major structural component of the basilar membrane ( 22 , 24 ).…”

“…From 2005, the occurrence of the COL4A1 gene mutation and associated hereditary disease has started to attract the attention ( 22 , 23 ). The COL4A1 gene is the major structural component of the basilar membrane ( 22 , 24 ). COL4A1 is associated with bone mineral density in different parts of the bone ( 25 , 26 ).…”

Novel COL4A1 mutations identified in infants with congenital hemolytic anemia in association with brain malformations

“…In 2016, Tomotaki et al reported a male infant with COL4A1-related disorder with severe hemolytic jaundice. His anemia improved after the red cell transfusion on day 29 without recurrence 6 . Maisonneuve et al reported a fetal case with severe anemia in association with cerebral ischemohemorrhagic damage revealed by ultrasonography, in whom a de novo COL4A1 mutation was identified 7 .…”