eP028: Neurological manifestations in PMM2 related congenital disorders of glycosylation (CDG): Insights into clinico-radiological characteristics and recommendations for follow-up


      PMM2-CDG is the most common N-linked glycosylation disorder. Neurological involvement is one of the major clinical features in individuals with PMM2-CDG. Understanding the neurological phenotype is essential as many treatments are on the horizon, and their ability to modify the neurological manifestations are yet to be understood.


      Prospective neurologic evaluation of patients with PMM2-CDG to systematically explore the neurologic phenotype, predict severity and to derive recommendations for clinical practice and research.


      Patients with biochemical and molecular confirmation of PMM2-CDG who were recruited along with other CDG to the Frontiers of Congenital Disorders of Glycosylation (FCDGC) natural history study were evaluated for neurological manifestations as a part of standard care.


      Thirty-two patients were included (7 females and 25 males). Mean age at diagnosis was 7 months (range 4 months to 32 years). Various diagnosis like spinal muscular atrophy, Prader-Willi syndrome and congenital muscular dystrophy were considered initially, before suspecting CDG. Mean age at assessment at our clinic was 11.42 years (range of 2 to 34 years). Only two patients were walking unassisted, the rest required assistance to walk. Socio-adaptive and language domains were relatively preserved when compared to motor development. Retinopathy was present in 10 (31%) and hearing loss requiring aids was seen in 6 (19%) patients.
      Cerebellar ataxia was the most common finding (97%) followed by myopathy (78%), neuropathy (78%), movement disorder (50%) and spasticity (19%). Seizures were present in 69% of patients with mean age at onset being 3 years (range 3 months to 24 years). Eleven of them both febrile and afebrile seizures, 4 had only febrile and 7 only afebrile seizures. Status epilepticus requiring hospital admission was seen in 28%. Antiepileptics tried were levetiracetam, oxcarbazepine, carbamazepine, phenytoin, clobazam, clonazepam and lacosamide. Three had medically refractory seizures, 3 with initially refractory seizures were currently under control, 16 had good seizure control from beginning.
      Total of 7 stroke like episodes (SLE) were seen in 6 patients, with precipitating factor being seizures in 4, infection in 2 and an accidental fall in one. Most of them recovered in a day. Two patients had normal imaging, whereas all others revealed progressive cerebellar atrophy. Mean score in Nijmegen Pediatric CDG rating scale was 23.1(range of 14 to 33). Statistically significant correlation was seen with seizures and SLE (p=0.004). No statistical significance was seen with head circumference, clinical features, imaging findings, Nijmegen scores or transferrin values with the severity of involvement, seizures, or SLE.


      Cerebellar ataxia is the most common neurological sign in PMM2-CDG. Patients with seizures are prone to develop SLE. Adequate seizure control might prevent SLE and progressive neurologic deterioration. Transferrin profile and Nijmegen scoring does not appear to correlate with neurological involvement or severity.