A scoring system to predict disease severity in
PGM1-CDG (former CDG It)
A treatable Congenital Disorder of Glycosylation
with no central nervous system involvement.
By Fiona Waddell
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publicationscdg@gmail.com
Sunnie Yan-Wai Wong, BA, MD/PhD Candidate at
Tulane University
School of Medicine (New
Orleans, USA) created with her team a rating scale to evaluate measurable clinical
features of PGM1-CDG (former CDG It). This is important for early recognition
and diagnosis, which is essential for proper management and improving clinical
outcome.
Congenital Disorders of Glycosylation (CDG) are a group of genetic diseases that
are caused by defects in protein glycosylation. Phosphoglucomutase-1 deficiency
(PGM1-CDG, read more
HERE) was recognised recently and one of the tasks of this enzyme is the
storage of sugar (energy), even if this energy is not needed, in order to
release energy when it is necessary. Another task of the enzyme is to paste
sugars to proteins. When this enzyme is not working, there may be a variety of
clinical manifestations, including hypoglycaemia, congenital malformations,
early-onset of dilated cardiomyopathy, growth retardation, hormonal
deficiencies, hepatopathy, haemostatic anomalies and myopathy. Interestingly,
PGM1-CDG is one of the few CDG's that has no central nervous system involvement
and has been clinically shown to be tratable; therefore, early diagnosis is
important.
Wong evaluated 27 patients with PGM1-CDG who were divided into 3 phenotype
groups: severe, moderate and mild. She and her team developed a scoring system,
the Tulane PGM1-CDG Rating Scale (TPCRS). This scale evaluates PGM1-CDG disease
severity based on the patients' clinical history and presentation. They examined
the relationship between genotype, enzyme activity and the TPCRS score.
The research showed that there was a great diversity in the phenotype spectrum.
Hepatopathy is the most frequent clinical manifestation, followed by
hypoglycaemia, congenital malformation and growth retardation. It also showed
that genotype and enzyme activity does not have any significant correlation with
the TPCRS score. There were 5 clinical features identified that are strongly
associated with one another and are predictive of disease severity: congenital
malformation, cardiac involvement, endocrine deficiency, myopathy and growth.
Congenital malformation and growth retardation can be evaluated by physical
examination, without the need for specific diagnostic testing and thus allow for
rapid assessment and initiation of therapy.
It is important to note that long-term follow-up data are not available for some
of the patients and disabling symptoms may appear later with time. Although
liver involvement and haemostatic anomalies do not have clear correlations with
disease severity, these clinical features are common in PGM1-CDG and require
timely and proper treatment. The TPCRS can be repeated on patients over time,
for monitoring disease progression and responsiveness to therapeutic treatment.