The role of automated analyzers in detecting abnormal granulation of leucocytes in lysosomal storage diseases: Maroteaux–Lamy disease


  • Conflict of interest: Nothing to report.

Correspondence to: Elisa Piva, UOC di Medicina di Laboratorio, Azienda Ospedaliera, via N. Giustiniani 1, 35128 Padova, Italy. E-mail:

A 3-year-old girl was referred to the Pediatric Emergency Room at Padua University-Hospital. Her parents reported two episodes of vomiting at home following an accidental fall from her bed while sleeping, with no apparent loss of consciousness. On admission she was alert, active, and responsive. A hematoma and swelling in the left parietal region were observed, in conjunction with multiple skeletal abnormalities, including scoliosis, short stature, and coxa valga. Neurological examination was normal. There was hepatomegaly while the spleen was not palpable.

A basic biochemical panel (glucose, creatinine, sodium, potassium, total protein, Alanine aminotranferease (ALT), aspartate aminotransferase (AST) and total bilirubin) was unremarkable, as was a complete blood count (CBC) performed with a Sysmex XE-2100 (Sysmex, Kobe, Japan) analyzer. However, the automated differential count showed an increase in the basophil percentage (5%, upper limit of normal 1%), prompting a review of the peripheral blood smear. Unusual granules in the cytoplasm of the granulocytes were detected. In a large number of neutrophils, granules resembled toxic granulation (Image 1a), while in other neutrophils some of the granules were larger and coarser than normal, with abnormal staining characteristics (Image 1b). Neutrophils also showed abnormal nuclear lobulation (Image 1c,d). In the eosinophils, the granules showed very abnormal characteristics that made the granules deep pink/blue (Image 1e,f). The morphological abnormalities, associated with the clinical features, led to the suspicion of a lysosomal storage disease, in particular Maroteaux–Lamy syndrome [1]. The diagnosis was confirmed by tests of urinary glycosaminoglycan analysis and genetic analysis (arylsulfatase B mutations) [2]. Mucopolysaccharidosis (MPS) are a group of lysosomal storage diseases caused by an inherited deficiency of an enzyme involved in the degradation of glycosaminoglycans. MPS VI, also known as Maroteaux–Lamy syndrome, is a rare autosomal recessive disease, characterized by variable systemic clinical manifestations, functional impairment, and very typical, striking granulation in the peripheral smear. Clinically there are severe, intermediate, and mild forms [3]. MPS VI is determined by mutations in the arylsulfatase B (ARSB) gene located in chromosome 5 (5q13–5q14) which result in reduced or completely impaired activity of arylsulfatase B, leading to the accumulation of incompletely degraded glycosaminoglycan (dermatan sulfate) in lysosomes. Since it is important to make an early diagnosis of MPS, the peripheral blood film should be examined whenever the suspicion of this disease exists. The slowly progressing form of the disease, which is characterized by later onset of symptoms due to lower levels of dermatan sulfate without visible or clinical symptoms of MPS VI, can also be detected on routine blood examination [4]. MPS VI is treatable by enzyme replacement therapy, and the earlier treatment is started, the better the outcome of a patient appears to be [5].

Figure 1.

Images from peripheral blood: (a) neutrophil showing granules resembling toxic granulation; (b) neutrophil in which granules were larger and coarser than normal, with abnormal staining; (c, d) non-lobed neutrophils with abnormalities in granules; (e, f) eosinophils showing deep pink-blue granules.

This case highlights the importance of careful review of the peripheral smear in all cases with basophilia detected by automated analysis. In this case, basophilia in the automated count turned out to be a pseudobasophilia, which however allowed the identification of a previously undiagnosed and potentially treatable metabolic disease.