Discussion.
PMM2-CDG can present as a multisystemic disease with a wide variety from
a mild to severe degree of clinical organ dysfunction and dysmorphology.
In a literature review on 933 patients with molecularly and/or
enzymatically confirmed PMM2-CDG, renal abnormalities seem to be
reported in 56 patients (6%). Among these, only 4 patients had
nephrotic syndrome (NS), which include many different underlying causes,
both acquired and genetic [3].
[4-7]. In the Hutchesson et al patient [4], NS started at age 8
wo. Urinary protein was 1377 mg/mmol of creatinine (n.v. <20)
and serum albumin 22 g/L (n.v. 30-50). He died at 106 days from
respiratory failure. Van der Knaap et al. [5] reported on a boy with
congenital NS. In the first 2–3 weeks he developed generalized oedema
and ascites with progressive severe proteinuria (1113 mg/mmol
creatinine) and hypoalbuminemia (9 g/L). Renal biopsy showed diffuse
mesangial sclerosis. He died at 2 months for sepsis and meningitis. Some
lysosomal enzymes were increased, leading to the CDG suspicion and the
PMM2-CDG diagnosis. Because all attention was focused on the NS, this
diagnosis was initially missed. Jamroz et al. [6] reported on a girl
with cardiorespiratory insufficiency on her first day. CMV infection was
diagnosed with pneumonia, endocarditis and NS. At 4 months she was
admitted with a typical PMM2-CDG phenotype, confirmed by enzymatic and
molecular analysis. She showed progressive deterioration with
pericardial effusion and ascites and died at 5 months due to heart
tamponade. In a review on 96 French patients with PMM2-CDG, Schiff et
al. [7] mentioned 2 patients with NS without providing any other
details. A mild to moderate proteinuria has already been reported in
1991 in 29 patients with the carbohydrate-deficient glycoprotein
syndrome [8], subsequently diagnosed as PMM2-CDG (though this is a
tubular proteinuria, while the NS proteinuria is glomerular).
Our reported case suggests not only to have PMM2-CDG patients undergo
routinary blood chemistry, urinary and instrumental examinations to
evaluate kidneys trend, but also and most important to consider such
possible diagnosis when assessing patients with renal involvement
without an established diagnosis or cause, mostly if presenting with
proteinuria and tubular proteinuria (whether in the nephrotic range or
not) and with positive history of neurological involvement. Although
renal involvement has been reported to date only in a minor percentage
of CDG patients, it should always be ruled out among patients in order
to avoid possible dangerous consequences and chronic damage.
What caused our patient NS is still not clear (CDG itself? The
pneumonia? A combination of both or else?). There has been no relapse
anyhow and her actual (at 13 years) urinary protein level is 61 mg/mmol
creatinine.
In conclusion, NS evidence in the context of a multisystem disorder with
neurological involvement should be reminiscent of PMM2-CDG.