Introduction:
The mucopolysaccharidoses (MPS) are a set of rare genetic disorders characterized by a lack of or malfunctioning of enzymes that metabolize glycosaminoglycans (GAGs) at the lysosomal level. They account for fewer than 0.1 percent of all genetic disorders. 1,2 MPS can be found in various forms worldwide. Coarse facial characteristics, cognitive retardation, hepatosplenomegaly, hernias, kyphoscoliosis, corneal clouding, and other clinical symptoms vary depending on the individual enzyme deficit. Different MPS exhibit comparable symptoms, especially MPS I and II; however, there are some differences, such as severe neurological issues in MPS III and hydrops fetalis in MPS VII.3 These clinical signs help diagnose, but early and precise diagnosis in the asymptomatic stage is critical for better outcomes. The diagnosis is confirmed by identifying the malfunctioning enzyme and searching for a mutation. For patient management and family screening, it is essential to recognize mucopolysaccharidosis. Novel approaches such as urinary and blood GAG tests, enzyme assays, and gene tests aid in diagnosing and subtyping MPS. 3,4 Based on experimental and clinical investigations, hematopoietic stem cell transplantation and enzyme replacement treatment have been established in the previous three decades. 5
MPS is divided into seven types, and eleven subtypes differentiated biochemically by the related enzyme deficit. The incidence of MPS varies depending on the geographic location. For instance, MPS II is the most prevalent in the study site (Asia), whereas in Europe, MPS I & MPS III are more prevalent. 3 MPS II or Hunter syndrome is the only X-linked-inherited mucopolysaccharidosis primarily affecting males with an incidence rate ranging from 0.38 to 1.09 per 100,000 live male births. However, no documented study in Bangladesh shows the prevalence of Hunter’s disease. 6 Besides, both MPS I and II present with hepatosplenomegaly, cognitive retardation, Dystosis multiplex (large dolichocephalic skull, thickened calvarium with hyperostosis of the cranium, boot-shaped Sella tursica, thickened clavicles, ovoid vertebral bodies with a peak like projection, tapering of the terminal phalanges, flared ribs, etc.), dysmorphic appearance, corneal clouding, and cardiac abnormalities. Additionally, MPS II has features of dermatological signs. MPS III has limited CNS involvement features and probable Dystosis multiplex and dysmorphic appearances7,8.
Confirmatory diagnosis of MPS can be made by urinary and blood GAGs test, enzyme assay, and gene test; moreover, this can be diagnosed antenatally by fibroblast enzymatic activity in amniotic fluid and marke d GAGs storage in fetal organs 9,10. A newborn screening program by enzymatic assay is recommended in the USA, Taiwan, and Italy. In the rest of the world, the newborn screening program doesn’t exist. The physicians are confronted with the issue of identifying MPS patients in the early stages of the disease before irreversible damage has occurred. 11 Moreover, most of these enzymatic studies are unavailable in resource-limited centers such us in Bangladesh. Hence a careful and critical approach with supportive imaging features of the skeletal survey following patient’s clinical features is essential for diagnosing MPS types 12,13. Attempts had been to diagnose the MPS types without the biochemical test. A mnemonic screening tool for MPS II (Hernia/Hearing, Unusual faces, Nasal obstruction, Tongue and Tonsils, enlarged liver and spleen, Respiration/Range of Motion) (Mnemonic – HUNTER) was developed by the Hunter Outcome Survey (HOS) group. This tool is 95% accurate for diagnosing MPS II or Hunter syndrome. 14 Additionally, few researchers from a neighboring country (Nepal) diagnosed MPS II from history, clinical features, and skeletal survey as they lack biochemical testing facilities in their limited-resource settings.12,15
Managing MPS entails halting the disease’s severity and enhancing one’s quality of life. Patients with MPS have several therapy choices, including palliative care, surgery, and disease-specific treatments such as Enzyme Replacement Therapy (ERT) and Hematopoietic Stem Cell Transplantation (HSCT). 3 However, to accept the treatment, detailed clinical evaluation and disease history must be considered 5. Although novel treatments such as substrate reduction therapy, pharmacological chaperone therapy, and gene therapy are becoming clinically available, early diagnosis is crucial to avail these treatment facilities. Many of these therapies, especially enzyme replacement therapy, have demonstrated the potential of alleviating the outcome and significantly raising the quality of life if started early in the disease 5. Overall, clinical evaluation, early identification, and rapid diagnosis of the cases are the key to a better outcome since the treatment in these cases is time-sensitive.