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.