Alder–Reilly Anomaly Leading to Incidental Diagnosis of MPS VII in an Asymptomatic Adult

ABSTRACT

Mucopolysaccharidosis type VII (MPS VII; Sly syndrome) is a rare autosomal recessive lysosomal storage disorder caused by deficiency of β‐glucuronidase due to pathogenic variants in the GUSB gene. Impaired degradation of glycosaminoglycans (GAGs) results in multiorgan dysfunction with highly variable clinical presentation, ranging from severe neonatal disease to attenuated adult phenotypes. We report an incidental diagnosis of MPS VII in a 31‐year‐old woman identified through routine laboratory testing. Review of a peripheral blood smear was prompted by automated hematology analyzer flags and revealed Alder–Reilly anomaly with characteristic aberrant leukocyte granulation. Subsequent biochemical analysis showed elevated urinary dermatan sulfate and heparan sulfate, alongside reduced β‐glucuronidase activity (~2%–3% of normal). Genetic testing of GUSB identified compound heterozygosity for a likely pathogenic frameshift variant (c.133_134del) and a missense variant (c.454G>A) previously associated with pseudodeficiency. Despite biochemical and genetic findings consistent with MPS VII, the patient exhibited no typical clinical manifestations, and detailed phenotyping showed no organ involvement. This case illustrates an atypical, asymptomatic presentation of MPS VII diagnosed in adulthood, in which Alder–Reilly anomaly served as a critical diagnostic clue. The combination of a null allele with a pseudodeficiency‐associated variant resulted in reduced enzyme activity without overt disease. These findings highlight the importance of peripheral blood smear evaluation in identifying lysosomal storage disorders and underscore the complexity of genotype–phenotype correlations in MPS VII.