Results.
We report the case of a now aged 13 yo female who manifested with
hypotonia, alternating strabismus and hypokinesia during her first
months of life. First words and walking with support were at 24 mo, thus
development was delayed. Metabolic (without serum transferrin IEF) and
genetic investigations were normal. Brain MRI showed incomplete
myelination, cardiac US an atrial septal defect and auditory evoked
potentials a maturation delay.
At 2 years she was admitted for lethargy. CT scan and cerebral MRI
angiography showed venous sinus thrombosis with widespread damage of
hypothalamus, thalamus and basal ganglia with cerebellar atrophy. She
subsequently developed a predominantly left quadriplegia with ataxia,
intentional tremor and seizures partially responding to treatment.
Until 3 yo she was frequently admitted for recurrent episodes of both
upper and lower airway infections. There was hypertransaminasemia
(AST-ALT: 564-571 U/L) but no clotting abnormalities.
At 4 years she presented a status epilepticus and was admitted to our
department. Pneumonia and NS (urine protein/creatinine ratio: 3.6 mg/mg,
n.v. <0.2mg/mg) were diagnosed, with oliguria, oedema,
hypertension and hypoalbuminemia (2.4 g/l; n.v.30-50). Steroids were
started (prednisone 60 mg/m2/day for 6 weeks, then 40 mg/m2/day for
other 6 weeks) with progressive clinical remission. Clotting factors
were altered (PT 15.6 sec, ratio 1.41; INR 1.39; aPTT 35.3 sec; INR
1.22; ATIII 8%, n.v. 70-120%); 1 month after the acute episode protein
S, protein C and AT III were 46% (n.v. 65-128%), 44% (72-142%) and
30% (70-120%) respectively. A CDG was suspected for the neurological
picture and the NS episode: serum
transferrin IEF confirmed a type 1 pattern with increase of di- and
asialotransferrin and decrease of tetrasialotransferrin. PMM2 activity
in leukocytes was 0.19 mU/mg protein (n.v. 3-5) and 2 PMM2 variants were
described at the molecular analysis, c.422G>A (p.R141H) and
c.95TA>GC (p.L32R). She now shows large and dysplastic
ears, no other dysmorphism. She walks with support and presents a normal
growth, though she still shows alternating strabismus and frequent
seizures under several antiepileptics. No retinitis pigmentosa. No other
thrombotic episodes nor renal relapses have been reported. Serum
transaminases have normalized.