Implementation of an Affordable Method for MPS Diagnosis from Urine Screening to Enzymatic Confirmation: Results of a Pilot Study in Morocco.

Naima Fdil,Imane Saab,Mohammed Bouskraoui,Fatiha Bennaoui,Nadia Slitine,Abdessamad Lalaoui,Aicha Ezoubeiri,Abdallah Karim,Abderahmane Daoudi,Luis Aldámiz-Echevarria,Noureddine Rada,Adil Fouad,Fernando Andrade,Rabiy Elqadiry,Es-Said Sabir,Domingo González-Lamuňo,Aicha Bourrahouat,Brahim Boualy

doi:10.7754/clin.lab.2019.190720

Abstract

Rapid and accurate diagnosis of mucopolysaccharidoses (MPS) is still a challenge due to poor access to screening and diagnostic methods and to their extensive clinical heterogeneity. The aim of this work is to perform laboratory biochemical testing for confirming the diagnosis of mucopolysaccharidosis (MPS) for the first time in Morocco. Over a period of twelve months, 88 patients suspected of having Mucopolysaccharidosis (MPS) were referred to our laboratory. Quantitative and qualitative urine glycosaminoglycan (GAG) analyses were performed, and enzyme activity was assayed on dried blood spots (DBS) using fluorogenic substrates. Enzyme activity was measured as normal, low, or undetectable. Of the 88 patients studied, 26 were confirmed to have MPS; 19 MPS I (Hurler syndrome; OMIM #607014/Hurler-Scheie syndrome; OMIM #607015), 2 MPS II (Hunter syndrome; OMIM #309900), 2 MPS IIIA (Sanfilippo syndrome; OMIM #252900), 1 MPS IIIB (Sanfilippo syndrome; OMIM #252920) and 2 MPS VI (Maroteaux-Lamy syndrome; OMIM #253200). Parental consanguinity was present in 80.76% of cases. Qualitative urinary glycosaminoglycan (uGAGs) assays showed abnormal profiles in 31 cases, and further quantitative urinary GAG evaluation and Thin Layer Chromatography (TLC) provided important additional information about the likely MPS diagnosis. The final diagnosis was confirmed by specific enzyme activity analysis in the DBS samples. The present study shows that the adoption of combined urinary substrate analysis and enzyme assays using dried blood spots can facilitate such diagnosis, offer an important tool for an appropriate supporting care, and a specific therapy, when available.

Highlights

High consanguinity, difficult access to accurate diagnostic tests, and costly therapies are all significant contributors to the lysosomal disease burden
The present study shows that the adoption of combined urinary substrate analysis and enzyme assays using dried blood spots can facilitate such diagnosis, offer an important tool for an appropriate supporting care, and a specific therapy, when available
Thin Layer Chromatography (TLC) was carried out for all patients with total GAG levels strongly or slightly elevated, all those patients suspected of MPS IV, even with a low urinary excretion of GAG (3 cases), and those patients exhibiting symptoms consistent with mucopolysaccharidosis, including the microlipidosis and several glycoprotein storage disorders

Summary

Introduction

Difficult access to accurate diagnostic tests, and costly therapies are all significant contributors to the lysosomal disease burden. The Mucopolysaccharidosis (MPS) is a group of metabolic disorders characterized by a deficiency in one of the lysosomal enzymes necessary for the catabolism of glycosaminoglycans (GAGs), formerly known as mucopolysaccharides [1]. Deficiency of these enzymes leads to a widespread accumulation of undegraded or partially degraded GAGs in different tissues and to excessive excretion of these substances in urine [2]. In Morocco, obtaining an early clinical MPS diagnosis has historically been a challenge and patients have not been diagnosed until more advanced stages of the disease. Affordable, easy and accurate testing of suspected patients is fundamental to diagnosis and management

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