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Author Notes:

Correspondence: H. A. Jinnah, M.D., Ph.D., Professor, Departments of Neurology, Human Genetics & Pediatrics, Emory University, Suite 6300 Woodruff Memorial Building, 101 Woodruff Circle, Atlanta GA, 30322, Phone: 404-727-9107, Fax: 404-712-8576, hjinnah@emory.edu

HFC and RJT contributed equally to this work.


Research Funding:

This work was supported in part by the Lesch-Nyhan Syndrome Children’s Research Foundation, the European Regional Development Fund (ERDF), and grants from the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III (Healthcare Research Fund of the Carlos III Health Institute; FIS, 15,10000) and from the Mutua Madrilena Fundation.

Dr. Hasan Cakmakli was supported by Turkish Scientific Council Postdoctoral Research Fellowship Grant-2219 and Turkish Hematology Council-HAUD award during his stay in the U.S.A.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Genetics & Heredity
  • HPRT1
  • hypoxanthine-guanine phosphoribosyltransferase
  • Lesch-Nyhan disease
  • macrocytic anemia
  • megaloblastic anemia
  • ACID

Macrocytic anemia in Lesch-Nyhan disease and its variants


Journal Title:

Genetics in Medicine


Volume 21, Number 2


, Pages 353-360

Type of Work:

Article | Post-print: After Peer Review


Purpose: Lesch–Nyhan disease is an inherited metabolic disorder characterized by overproduction of uric acid and neurobehavioral abnormalities. The purpose of this study was to describe macrocytic erythrocytes as another common aspect of the phenotype. Methods: The results of 257 complete blood counts from 65 patients over a 23-year period were collected from 2 reference centers where many patients are seen regularly. Results: Macrocytic erythrocytes occurred in 81–92% of subjects with Lesch–Nyhan disease or its neurological variants. After excluding cases with iron deficiency because it might pseudonormalize erythrocyte volumes, macrocytosis occurred in 97% of subjects. Macrocytic erythrocytes were sometimes accompanied by mild anemia, and rarely by severe anemia. Conclusion: These results establish macrocytic erythrocytes as a very common aspect of the clinical phenotype of Lesch–Nyhan disease and its neurological variants. Macrocytosis is so characteristic that its absence should prompt suspicion of a secondary process, such as iron deficiency. Because macrocytosis is uncommon in unaffected children, it can also be used as a clue for early diagnosis in children with neurodevelopmental delay. Better recognition of this characteristic feature of the disorder will also help to prevent unnecessary diagnostic testing and unnecessary attempts to treat it with folate or B12 supplements.

Copyright information:

© 2018, American College of Medical Genetics and Genomics.

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