-
Frontiers in Neurology 2020CAD encodes a multifunctional enzyme involved in pyrimidine biosynthesis, and pyrimidine can be alternatively recycled from uridine. Trio whole-exome sequencing...
CAD encodes a multifunctional enzyme involved in pyrimidine biosynthesis, and pyrimidine can be alternatively recycled from uridine. Trio whole-exome sequencing identified CAD compound heterozygous mutations in a new male patient with global developmental delay (DD), refractory epilepsy, and anemia with anisopoikilocytosis. We further reviewed all published cases with CAD deficiency. Five patients were collected from two publications, including three males and two females, and all presented with DD, drug-resistant epilepsy, and anemia with anisopoikilocytosis. Four out of six patients (including the present case) were supplemented with uridine, which led to immediate cessation of seizures, resolved anemia with anisopoikilocytosis, and progress in global development. The other two patients, who were not treated with uridine, died at the ages of 4 and 5 years. In summary, CAD deficiency is probably a treatable neurometabolic disorder.
PubMed: 32117025
DOI: 10.3389/fneur.2020.00064 -
Annales de Biologie Clinique Feb 2020Hemoglobin D-Punjab is a common hemoglobin variant in India but very rare in Morocco. Often, its presence has minimal or no clinical impact. Its heterozygous association...
UNLABELLED
Hemoglobin D-Punjab is a common hemoglobin variant in India but very rare in Morocco. Often, its presence has minimal or no clinical impact. Its heterozygous association with β-thalassemia is exceptional. The purpose of the study is to describe the epidemiological, diagnostic and prophylactic aspects of hemoglobinosis D-Punjab from a family case study.
MATERIAL AND METHODS
Case study of hemoglobinosis D-Punjab in a Moroccan family, diagnosed at the Laboratory of Biochemistry-Toxicology of the Mohammed V Military Teaching Hospital. The biological study was based on iron and hemolysis checkups, hemogram and study of hemoglobin (electrophoresis in alkaline and acid medium, high performance liquid chromatography). The index patient also benefited from sequencing by molecular biology.
RESULTS
The index patient was heterozygous D-Punjab/β-thalassemia, confirmed by molecular biology. Two of her sisters had the same hemoglobin profile. At electrophoresis, all three had hemoglobin D-Punjab higher than 90%, hemoglobin A less than 1% and hemoglobin A higher than 6%. The results of the three hemograms showed similar abnormalities (pseudo-polycythemia, hypochromia, microcytosis, anisopoikilocytosis). Six other members of the family had a thalassemic trait and another three had heterozygous hemoglobinosis D-Punjab.
CONCLUSION
Hemoglobin D-Punjab remains extremely rare in Morocco and very poorly documented in the literature. The number of reported cases is expected to raise due to increasing migration. Biologist advisory services require a precise diagnosis in order to give correct genetic counseling.
Topics: Adolescent; Adult; Child; Family; Female; Genetic Association Studies; Hemoglobins, Abnormal; Humans; Male; Middle Aged; Morocco; Pedigree; beta-Thalassemia
PubMed: 32108581
DOI: 10.1684/abc.2020.1523 -
Journal of Pediatric Hematology/oncology Nov 2019Pyrimidine-5-nucleotidase (P5'N-1) deficiency is a rare nonspherocytic hemolytic anemia due to pyrimidine nucleotide deposition within erythrocytes. This rare...
Pyrimidine-5-nucleotidase (P5'N-1) deficiency is a rare nonspherocytic hemolytic anemia due to pyrimidine nucleotide deposition within erythrocytes. This rare erythrocyte disorder shows autosomal recessive inheritance with mutation of the pyrimidine-5'-nucleotidase gene, which is localized on 7p15-p14. Consanguinity of parents increases the probability of disease with novel mutations. Here, we report a 12-year-old boy with a delayed diagnosis of P5'N deficiency whose parents were consanguineous. He had a hemoglobin level of 7.5 g/dL, mean corpuscular volume of 93 fL, 7% reticulocyte, and lactate dehydrogenase of 678 IU/L. A peripheral blood smear showed polychromasia, marked anisopoikilocytosis with schistocytes, elliptocytes, stomatocytes, spherocytes, dacryocyte, and basophilic stippling in red blood. Decreased purine/pyrimidine ratio was 1.07 (normal range=1.4 to 2.98). Molecular analysis with direct DNA sequencing of the NT5C3 gene, codifying for P5'N-1, revealed the presence of a novel homozygous mutation, c393-394delTA, in the gene coding P5'N enzyme in the patient. To our knowledge, this is a newly defined mutation in P5'N deficiency.
Topics: 5'-Nucleotidase; Anemia, Hemolytic, Congenital; Base Sequence; Child; Glycoproteins; Humans; Male; Sequence Deletion
PubMed: 30951028
DOI: 10.1097/MPH.0000000000001482