Hereditary fructose intolerance mimicking a biochemical phenotype of mucolipidosis: A review of the literature of secondary causes of lysosomal enzyme activity elevation in serum

Abstract

We describe a patient with failure to thrive, hepatomegaly, liver dysfunction, and elevation of multiple plasma lysosomal enzyme activities mimicking mucolipidosis II or III, in whom a diagnosis of hereditary fructose intolerance (HFI) was ultimately obtained. She presented before introduction of solid foods, given her consumption of a fructose-containing infant formula. We present the most extensive panel of lysosomal enzyme activities reported to date in a patient with HFI, and propose that multiple enzyme elevations in plasma, especially when in conjunction with a normal plasma α-mannosidase activity, should elicit a differential diagnosis of HFI. We also performed a review of the literature on the different etiologies of elevated lysosomal enzyme activities in serum or plasma. © 2016 Wiley Periodicals, Inc.

Measurement of lysosomal enzyme activities: A technical standard of the American College of Medical Genetics and Genomics (ACMG)

“…Finally, increased plasma activity of ≥1 lysosomal enzymes has also been described in other conditions with abnormal glycosylation or glycoprotein trafficking, including congenital disorders of glycosylation, galactosemia (untreated), hereditary fructose intolerance, Lowe syndrome, diabetes, and cancer. 60 On rare occasions, enzyme testing may be normal when an LSD is highly suspected. In this situation, it is important to consider whether cofactors and/or activators of these enzymes may be responsible for the clinical findings.…”

Transferrin isoelectric focusing for the investigation of congenital disorders of glycosylation: analysis of a ten-year experience in a Brazilian center

“…It is caused by a deficiency in aldolase B enzyme activity and, therefore, fructose-1 P accumulates in liver cells, resulting in the inhibition of phosphomannose isomerase, an enzyme present in the early stages of protein glycosylation. 17 , 18 …”

GNPTAB c.2404C > T nonsense mutation in a patient with mucolipidosis III alpha/beta: a case report

“…The generalized increase in plasma lysosomal enzyme activity provided an important diagnostic clue to establishing the biochemical and genetic diagnosis in this case. While specific patterns of enzyme activity elevation has been reported and applied in simplified, targeted screening strategies [ 27 ], it should perhaps be emphasized that only the use of multi-enzyme activity paneling would allow the most sensitive detection simultaneous differentiation from the phenotypically-similar MPSs and other inborn metabolic defects [ 28 ]. Of note, the more recently developed tandem mass spectrometry assays have allowed the determination of multiple lysosomal enzyme activity [ 29 , 30 ] and GAG levels [ 31 ] from a DBS sample, which can be transported to a reference laboratory by regular mail.…”