Alder-Reilly Anomaly: Morphologic Clue in a Patient with Hunter Syndrome

Alder-Reilly Anomaly: Morphologic Clue in a Patient with Hunter Syndrome
Author: Blaire Anderson; Regina Ondrasik, MD; Prabhjot Kaur, MD
Category: Myeloid Disorders > Lysosomal storage disorders
Published Date: 04/20/2022

A peripheral smear review was requested on a 12 year-old presenting with anemia. The peripheral smear demonstrated moderate normochromic, microcytic anemia and mild leukocytosis due to an absolute lymphocytosis (5.09 K/uL). Lymphocyte morphology was notable for cytoplasmic metachromatic inclusions with circumferential clearing described as Alder-Reilly anomaly, characteristically present in congenital mucopolysaccharidosis disorders (panels A-D; Wright-Giemsa stain, objective magnification 100x, total magnification 1000x).

Communication with the clinical team revealed a past history of mucopolysaccharidosis II (Hunter Syndrome) with associated cardiomyopathy, developmental delay, progressive hearing loss, and current presentation for acute-on-chronic respiratory distress. Hunter Syndrome is an X-linked recessive disorder caused by an alteration in the gene encoding iduronidate-2-sulfatase, resulting in deficiency of iduronidate-2-sulfatase and the accumulation of heparan sulfate and dermatan sulfate in organs and tissues1.  The cytoplasmic inclusions are composed of acid mucopolysaccharides, which are indigestible in patients with mucopolysaccharidoses4.  The Alder-Reilly anomaly may clue in the consideration for mucopolysaccharidosis in an individual without an established diagnosis.   Indeed there are reported cases of MPS IH (Hurler Syndrome) and MPS VII (Sly Syndrome) diagnosed after the discovery of Alder-Reilly cells in peripheral blood smears.2,3 In granulocytes they may resemble toxic granules, however these inclusions have a distinct appearance within lymphocytes.



1.         Simona S, Falvo F, Apa R, et al. Genetics and Gene Therapy in Hunter Disease. Curr Gene Ther. 2018;18(2). doi:10.2174/1566523218666180404155759

2.         Goudji CW, Schick T, Cherkaoui S, et al. A fortuitous but characteristic blood smear observation allowing a late diagnosis of MPS-VII. Clin Chem Lab Med. 2021;0(0). doi:10.1515/CCLM-2021-0966

3.         Bhuyan P, Singh B, Chakrabarty S, Mohanty N, Agarwal M, Satpathy S. Alder-Reilly Anomaly in Hurler’s Syndrome in a Neonate: A Rare Case Report. Indian J Hematol Blood Transfus. 2013;29(3):184-186. doi:10.1007/S12288-012-0178-3

4.         Jandl JH. Blood : Textbook of Hematology. 2nd ed. Lippincott Williams and Wilkins; 1996.