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.