MPS VII - Extending the classical phenotype.

Mucopolysaccharidosis VII (or Sly syndrome) is an autosomal recessive disorder characterised by a deficiency in the enzyme Beta-glucuronidase (GUSB). Partial degradation of glycosaminoglycans (GAGs); chondroitin sulfate (CS), dermatan sulfate (DS) and heparan sulfate (HS) results in the accumulation of these fragments in the lysosomes of many tissues, eventually leading to multisystem damage. In some cases, early diagnosis on clinical grounds alone can be difficult due to the extreme variability of the clinical presentation and disease progression. We present a case report of a 31-year-old male patient diagnosed with MPS VII at the age of 28, who multiple specialists saw without suspecting the diagnosis due to the unusual presentation. The patient presented with a history of developmental delay, scoliosis, kyphosis, corneal clouding, abnormal gait, short stature, hearing impairment, slightly coarse facial features and progressive deterioration of fine motor skills since childhood. The patient had inguinal hernia repair at around 12 months, bilateral hearing impairment with a left bone-anchored hearing aid, and spinal surgery. During spinal surveillance MPS VII was suspected by a spinal surgeon with interest in MPS, and the diagnosis confirmed with a deficiency in beta-glucuronidase in leucocytes and marginally elevated urinary GAGs. Next-generation sequencing identified two mutations in the GUSB gene (OMIM 611499), c.526C > T p.(Leu176Phe) and c.1820G > C p.(Gly607Ala). Although the patient exhibited features of the severe form of non-classical manifestations, his metabolic condition has remained reasonably stable, surviving into adulthood with only symptomatic treatment. We present the ever-expanding phenotypic spectrum of this ultra-rare disease.

The contribution of immunocytochemistry in diagnostic cytology. Comparison and evaluation with immunohistology.

This study reports on the use and evaluation of immunocytochemistry in diagnostic cytology by correlation with (immuno)histology. The cytologic material was collected during a period of 3 years. Sixty-four patients were selected and studied retrospectively. The reactivity of a number of polyclonal and monoclonal antibodies was investigated and applied to a diverse group of tumors. Marker expression on routine cytologic and histologic material was compared and the use of immunocytochemistry in diagnosis was evaluated. Immunocytochemistry proved to be an easy and valuable technique for the identification and classification of tumor cells, and there was a good concordance with immunohistology. A discrepancy in marker expression was found in 10% of the slides that were investigated. Immunocytochemistry led to a misdiagnosis in only four cases; however, in these cases cytology alone would not have led to the correct diagnosis. The causes for the discrepancies are discussed. It is estimated that immunocytochemistry contributed to the diagnosis of approximately 50% of the cases, supplying either additional or essential information. A wide variety of markers can be applied reliably on cytologic preparations. The use of panels of antibodies is mandatory.