Carmen Barba1, Francesca Darra2, Raffaella Cusmai3, Elena Procopio4, Carlo Dionisi Vici5, Liesbeth Keldermans6, Sandrine Vuillaumier-Barrot7, Dirk J Lefeber8, Renzo Guerrini1,9. 1. Pediatric Neurology Unit and Laboratories, A. Meyer Children's Hospital - University of Florence, Florence, Italy. 2. Child Neuropsychiatry, University-Hospital of Verona, Verona, Italy. 3. Neurology Unit, Bambino Gesù Children's Hospital, Rome, Italy. 4. Metabolic Unit, A. Meyer Children's Hospital - University of Florence, Florence, Italy. 5. Metabolic Unit, Bambino Gesù Children's Hospital, Rome, Italy. 6. Centrum Menselijke Erfelijkheid, UZ Leuven, Leuven, Belgium. 7. Biochemistry and Genetic Laboratory, AP-HP, Bichat Hospital, Paris, France. 8. Department of Neurology, Translational Metabolic Laboratory, Radboud University Medical Center, Nijmegen, the Netherlands. 9. IRCCS Stella Maris, Pisa, Italy.
Abstract
AIM: Epilepsy is commonly observed in congenital disorders of glycosylation (CDG), but no distinctive electroclinical pattern has been recognized. We aimed at identifying a characteristic clinical presentation that might help targeted diagnostic work-up. METHOD: Based on the initial observation of an index case with CDG and migrating partial seizures, we evaluated 16 additional children with CDG and analysed their clinical course, biochemical, genetic, electrographic, and imaging findings. RESULTS: Four of 17 consecutively observed children with CDG (three females, one male) were first referred between the first and fourth month of life, after early onset of migrating partial seizures. All four patients manifested developmental delay, microcephaly, and multi-organ involvement. Magnetic resonance imaging disclosed cerebral and cerebellar atrophy. Isoelectrofocusing of transferrin, enzymatic studies, and lipid-linked oligosaccharide analysis indicated CDG-I. Genetic testing demonstrated either homozygous or compound heterozygous variants involving the ALG3 gene in patients 1 and 3, the RFT1 gene in patient 2, and the ALG1 gene in patient 4. At last follow-up, patients 1 and 2 were 5 and 3(1/2) years old. Patients 3 and 4 had died due to respiratory failure during pneumonia and refractory status epilepticus respectively. INTERPRETATION: Children with migrating partial seizures and concomitant multisystem involvement should be investigated for CDG.
AIM: Epilepsy is commonly observed in congenital disorders of glycosylation (CDG), but no distinctive electroclinical pattern has been recognized. We aimed at identifying a characteristic clinical presentation that might help targeted diagnostic work-up. METHOD: Based on the initial observation of an index case with CDG and migrating partial seizures, we evaluated 16 additional children with CDG and analysed their clinical course, biochemical, genetic, electrographic, and imaging findings. RESULTS: Four of 17 consecutively observed children with CDG (three females, one male) were first referred between the first and fourth month of life, after early onset of migrating partial seizures. All four patients manifested developmental delay, microcephaly, and multi-organ involvement. Magnetic resonance imaging disclosed cerebral and cerebellar atrophy. Isoelectrofocusing of transferrin, enzymatic studies, and lipid-linked oligosaccharide analysis indicated CDG-I. Genetic testing demonstrated either homozygous or compound heterozygous variants involving the ALG3 gene in patients 1 and 3, the RFT1 gene in patient 2, and the ALG1 gene in patient 4. At last follow-up, patients 1 and 2 were 5 and 3(1/2) years old. Patients 3 and 4 had died due to respiratory failure during pneumonia and refractory status epilepticus respectively. INTERPRETATION:Children with migrating partial seizures and concomitant multisystem involvement should be investigated for CDG.
Authors: C Paketci; P Edem; S Hiz; E Sonmezler; D Soydemir; G Sarikaya Uzan; Y Oktay; E O'Heir; S Beltran; S Laurie; A Töpf; H Lochmuller; R Horvath; U Yis Journal: Brain Dev Date: 2020-05-07 Impact factor: 1.961
Authors: Hind Alsharhan; Bobby G Ng; Earnest James Paul Daniel; Jennifer Friedman; Eniko K Pivnick; Amal Al-Hashem; Eissa Ali Faqeih; Pengfei Liu; Nicole M Engelhardt; Kierstin N Keller; Jie Chen; Pamela A Mazzeo; Jill A Rosenfeld; Michael J Bamshad; Deborah A Nickerson; Kimiyo M Raymond; Hudson H Freeze; Miao He; Andrew C Edmondson; Christina Lam Journal: J Inherit Metab Dis Date: 2021-03-01 Impact factor: 4.750
Authors: Martina Farolfi; Anna Cechova; Nina Ondruskova; Jana Zidkova; Bohdan Kousal; Hana Hansikova; Tomas Honzik; Petra Liskova Journal: BMC Ophthalmol Date: 2021-06-05 Impact factor: 2.209