Mucopolysaccharidosis type <scp>VII</scp> diagnosed from a peripheral blood smear
Authors: Michela Pelloso, Silvia Zuin, Francesca Tosato, Jenny Zuin, Paola Fogar, Elisa Piva, Alberto Burlina, Mario Plebani
Journal: American Journal of Hematology (2020)

We present the case of a 17-year old girl admitted to the Pediatric Department of the Padua University-Hospital for mental impairment and muscle-skeletal abnormalities. The girl was born in Senegal from unrelated parents; childbirth was natural and uncomplicated. Despite normal growth in the first years of her life, all stages of psychomotor development were delayed (first words at 2 years, first walking at 5 years). At age 17, bone deformities, severe walking disability, moderate tosevere mental impairment, and aortic valve insufficiency were present. None of her relatives showed similar symptoms. Congenital myopathy or hereditary motor (+/− sensitive) neuropathy were considered. Blood electrolytes, glucose, creatinine, liver enzymes, bilirubin and cholesterol were in the normal range; CRP was elevated (in the absence of fever or inflammation); bone metabolism indexes were altered (elevated bone alkaline phosphatase, urinary collagen degradation products and PTH; decreased vitamin D). The complete blood count was carried out on a Sysmex XE-2100 analyzer (Sysmex, Kobe, Japan), which detected normocytic anemia and basophilia, which prompted an examination of the peripheral blood smear. Atypical granules were seen in the cytoplasm of eosinophils, basophils, and monocytes. Eosinophils and basophils showed coarse purple granules with a white outline in the cytoplasm; monocytes were filled with dense and minute purple-bluish granules. Nuclear morphology appeared to be normal in all cell types (Image 1A-F). Flow cytometry analysis demonstrated a normal monocyte population (CD33+ CD64+ HLA-DR+ CD6-) except for bimodal expression of CD14 and aberrant expression of CD15 (Image 1G-J). The peripheral smear findings prompted urinary glycosaminoglycans dosage (chondroitin sulfate, dermatan sulfate and heparan sulfate) and genetic screening for lysosomal storage diseases, which led to the diagnosis of mucopolysaccharidosis type VII (also known as Sly syndrome). It is one of the rarest types of mucopolysaccharidosis. The exact incidence of MPS VII is unknown, although it is estimated to occur in 1 in 250 000 newborns, while the prevalence at birth is reported to range between 1/345000-1/50000001.1, 2 This exceptionally rare autosomal recessive disease is caused by homozygosis for NM_000181.3(GUSB):c.1856 C > T p.Ala619Val, resulting in marked deficiency of beta-glucuronidase. This lysosomal enzyme is key in the breakdown of glycosaminoglycans. In presence of a loss-of-function mutation of this enzyme, glycosaminoglycans accumulate in different tissues, leading to several deformities and different organ dysfunctions; the clinical spectrum of the disease extends from mild to severe, but in all cases life expectancy is decreased.2 Early diagnosis is key in this disease since enzyme replacement therapy (vestronidase alfa-vjbk) is available.3 In this case, detection of pseudo-basophilia by automated CBC analysis and careful review of the peripheral blood smear were important in selecting the appropriate diagnostic pathway. Prior reports have also highlighted the major role that automated CBC analysis and peripheral smear review play in the diagnosis of rare metabolic diseases.4, 5 Data sharing not applicable to this article as no datasets were generated or analysed during the current study.