|Year : 2017 | Volume
| Issue : 1 | Page : 33-35
A case of hunter syndrome and Alder-Reilly anomaly
Nour AlMozain1, Nasir A Bakshi2
1 Hematology Section, Department of Pathology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia
2 Hematopathology Section, Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
|Date of Web Publication||12-Apr-2017|
Nasir A Bakshi
Hematopathology Section, Department of Pathology & Laboratory Medicine, King Faisal Specialist Hospital & Research Centre, PO Box 3354, Riyadh 11211
Source of Support: None, Conflict of Interest: None
A 2-year-old boy presented with delayed speech, hydrocephalus, skeletal deformities, and right-sided hydrocele. On investigation, the peripheral smear revealed Alder–Reilly anomaly in the neutrophils suggesting mucopolysaccharidosis (MPS). Molecular studies were performed, which showed results indicative of diagnosis of either MPS type I Hurler–Scheie or type II Hunter syndrome. Enzyme assays confirmed the diagnosis of MPS type II Hunter syndrome. We present this rare case to highlight the association of Alder–Reilly anomaly in Hunter syndrome and MPS.
Keywords: Alder–reilly, hunter syndrome, mucopolysaccharidosis, Case Report
|How to cite this article:|
AlMozain N, Bakshi NA. A case of hunter syndrome and Alder-Reilly anomaly. J Appl Hematol 2017;8:33-5
| Case Report|| |
A 2-year-old male child was referred to pediatric hematology bone marrow transplant for allogeneic cord blood transplant. His disease history dates back to the neonatal period. The child was born by an uneventful vaginal delivery. Motor milestones were normal for age, but speech was delayed. He had no back deformities, no history of seizures, hearing deficit, or corneal cloudiness. He had one normal sister. There was no family history of any similar disorder, although he was born of consanguineous marriage (parents were cousins). Physical examination showed hydrocephalus and right-sided hydrocele but no organomegaly or lymphadenopathy. His CBC showed a WBC count of 6.13 × 109/L, RBC count of 3.35 × 1012/L, Hb count of 106 g/L, Hct of 0.311, MCV of 92.8 fL, MCH of 31.6 pg, MCHC of 341 g/L, and RDW of 14%. Platelet count was low at 64 × 109/L. Peripheral blood smear showed abnormal granulations and vacuolation in the neutrophils and monocytes. Lymphocytes showed many large metachromatic inclusions surrounded by halo-like clearing [Figure 1]a and [Figure 1]b. Other laboratory tests including PT, PTT, INR, serum electrolytes, urea, creatinine, serum albumin, globulin, total bilirubin, AST, ALT, and alkaline phosphatase were within normal limits. Echocardiogram showed tiny foramen ovale with trivial mitral regurgitation. Skeletal survey showed dysostosis multiplex with bilateral developmental dysplasia of the hip. On the basis of the clinical picture and bony changes, he was provisionally diagnosed as having mucopolysaccharidosis (MPS) type 6 or Maroteaux–Lamy syndrome. Molecular studies were performed, which showed results indicative of diagnosis of either MPS type I Hurler–Scheie syndrome (alpha-l-iduronidase deficiency) or type II Hunter syndrome (iduronate sulfatase deficiency). Enzyme assays confirmed the diagnosis of MPS type II Hunter syndrome. The patient was given enzyme replacement therapy. This was followed by conditioning chemotherapy, and finally, the patient underwent allogeneic cord blood transplant. Post-transplant course was uneventful. He was supported by multiple platelet and blood transfusions; however, he showed no features of engraftment by 6 weeks following transplant. After restarting enzyme replacement therapy, an allogeneic, matched unrelated bone marrow transplant was performed.
|Figure 1: (a) Prominent dark staining and coarse cytoplasmic granules in polymorphonuclear neutrophil similar to toxic granules but larger and coarser. Wright–Giemsa stain 1000. (b) A lymphocyte from the same patient remarkable for the presence of many cytoplasmic metachromatic granules, which appear to be within small vacuoles. Wright–Giemsa stain 1000.|
Click here to view
| Discussion|| |
Alder–Reilly anomaly is a rare but an interesting morphologic finding characterized by large, intensely metachromatic inclusions or granules, also referred to as “Reilly bodies,” in the cytoplasm of neutrophils, lymphocytes, and monocytes usually also accompanied by defects in eosinophilic and basophilic granules. It was first described by Alder in 1939 and by Reilly in 1941; accordingly, it is known also as Alder–Reilly anomaly. It is typically associated with the genetic MPSs. The basic pathogenesis is that patients with MPSs lack the lysosomal enzymes necessary to break down mucopolysaccharides in the cytoplasm. Dense azurophilic granules, resembling toxic granulation in neutrophils, are seen in all leukocytes. However, these should not be confused with toxic granulations in neutrophils, which are characteristically present in a background of sepsis, infection, or myeloid growth factor therapy.
Alder–Reilly granules are bigger, coarser, and most characteristically present in lymphocytes as well as monocytes. Sometimes the metachromatic granules appear to be surrounded by a clear zone especially in lymphocytes, as demonstrated by the current case.
In Hunter syndrome (MPS II), one of the subtypes of genetic MPS, there is deficiency of enzyme iduronate 2-sulfatase (IDS) caused by mutations in the gene encoding for IDS, which is located on chromosome Xq28, which results in storage of heparan and dermatan sulfate., Although X-linked, cases in females have been documented., Both severe and mild forms of Hunter syndrome occur as part of a wide clinical spectrum., The severe form shares features with Hurler syndrome, including abnormal facial appearance, hepatosplenomegaly, cardiovascular disorder due to mucopolysaccharide deposits, dysostosis with dwarfism, neurocognitive decline, and deafness. However, Hunter syndrome is differentiated by its later onset (1–2 years of age), slower clinical course, and absence of corneal clouding. Survival to the teens or twenties is common. The mild form is similar to Scheie syndrome, although patients having Hunter syndrome often have more coarsened facies compared to the former. Affected patients usually have normal intelligence and can survive into the sixth or seventh decade of life.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Neufeld EF, Muenzer J. The mucopolysaccharidoses. In: Scriver C, Beaudet AL, Valle D, Sly W, editors. The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill 2001. p. 3421.
Hopwood JJ, Bunge S, Morris CP, Wilson PJ, Steglich C, Beck M et al.
Molecular basis of mucopolysaccharidosis type II: Mutations in the iduronate-2-sulphatase gene. Hum Mutat 1993;2:435-42.
Tuschl K, Gal A, Paschke E, Kircher S, Bodamer OA. Mucopolysaccharidosis type II in females: Case report and review of literature. Pediatr Neurol 2005;32:270-2.
Sukegawa K, Song XQ, Masuno M, Fukao T, Shimozawa N, Fukuda S et al.
Hunter disease in a girl caused by R468Q mutation in the iduronate-2-sulfatase gene and skewed inactivation of the X chromosome carrying the normal allele. Hum Mutat 1997;10:361-7.
5.Burton BK, Giugliani R. Diagnosing Hunter syndrome in pediatric practice: Practical considerations and common pitfalls. Eur J Pediatr 2012;171:631-9.
Wraith JE, Scarpa M, Beck M, Bodamer OA, De Meirleir L, Guffon N et al.
Mucopolysaccharidosis type II (Hunter syndrome): A clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr 2008;167:267-77.
Kampmann C, Beck M, Morin I, Loehr JP. Prevalence and characterization of cardiac involvement in Hunter syndrome. J Pediatr 2011;159:327-31.
Wappner RS. Lysosomal storage disorders. In: McMillan JA, Feigin RD, DeAngelis C, Jones MD, editors. Oski’s Pediatrics. Principles and Practice. 4th ed. Philadelphia: Lippincott, Williams & Wilkins; 2006. p. 2199.