A Brassier1, V Valayannopoulos1, N Bahi-Buisson2, Elsa Wiame3, L Hubert1, N Boddaert4, A Kaminska2, F Habarou5, I Desguerre2, E Van Schaftingen3, C Ottolenghi5, P de Lonlay6. 1. Centre de Référence des Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte (MaMEA), Hôpital Necker-Enfants Malades, APHP, Université Paris Descartes, Institut Imagine, Paris, France. 2. Service de Neuropédiatrie et explorations fonctionnelles, Hôpital Necker-Enfants Malades, Université Paris Descartes, Institut Imagine, Paris, France. 3. de Duve Institute, Université Catholique de Louvain, Brussels, Belgium. 4. Service de Radiologie pédiatrique, Hôpital Necker-Enfants Malades, Université Paris Descartes, Institut Imagine, Paris, France. 5. Service de Biochimie spécialisée, Hôpital Necker-Enfants Malades, Université Paris Descartes, Inserm U747, Paris, France. 6. Centre de Référence des Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte (MaMEA), Hôpital Necker-Enfants Malades, APHP, Université Paris Descartes, Institut Imagine, Paris, France. Electronic address: pascale.delonlay@nck.aphp.fr.
Abstract
OBJECTIVE AND PATIENTS: We report on two new cases of serine deficiency due respectively to 3-phosphoglycerate dehydrogenase (PHGDH) deficiency (Patient 1) and phosphoserine aminotransferase (PSAT1) deficiency (Patient 2), presenting with congenital microcephaly (<3rd centile at birth) and encephalopathy with spasticity. Patient 1 had also intractable seizures. A treatment with oral l-serine was started at age 4.5 years and 3 months respectively. RESULTS: Serine levels were low in plasma and CSF relative to the reference population, for which we confirm recently redefined intervals based on a larger number of samples. l-Serine treatment led in patient 1 to a significant reduction of seizures after one week of treatment and decrease of electroencephalographic abnormalities within one year. In patient 2 treatment with l-serine led to an improvement of spasticity. However for both patients, l-serine failed to improve substantially head circumference (HC) and neurocognitive development. In a couple related to patient's 2 family, dosage of serine was performed on fetal cord blood when the fetus presented severe microcephaly, showing reduced serine levels at 30 weeks of pregnancy. CONCLUSIONS: l-Serine treatment in patients with 2 different serine synthesis defects, led to a significant reduction of seizures and an improvement of spasticity, but failed to improve substantially neurocognitive impairment. Therefore, CSF and plasma serine levels should be measured in all cases of severe microcephaly at birth to screen for serine deficiency, as prompt treatment with l-serine may significantly impact the outcome of the disease. Reduced serine levels in fetal cord blood may also be diagnostic as early as 30 weeks of pregnancy.
OBJECTIVE AND PATIENTS: We report on two new cases of serine deficiency due respectively to 3-phosphoglycerate dehydrogenase (PHGDH) deficiency (Patient 1) and phosphoserine aminotransferase (PSAT1) deficiency (Patient 2), presenting with congenital microcephaly (<3rd centile at birth) and encephalopathy with spasticity. Patient 1 had also intractable seizures. A treatment with oral l-serine was started at age 4.5 years and 3 months respectively. RESULTS:Serine levels were low in plasma and CSF relative to the reference population, for which we confirm recently redefined intervals based on a larger number of samples. l-Serine treatment led in patient 1 to a significant reduction of seizures after one week of treatment and decrease of electroencephalographic abnormalities within one year. In patient 2 treatment with l-serine led to an improvement of spasticity. However for both patients, l-serine failed to improve substantially head circumference (HC) and neurocognitive development. In a couple related to patient's 2 family, dosage of serine was performed on fetal cord blood when the fetus presented severe microcephaly, showing reduced serine levels at 30 weeks of pregnancy. CONCLUSIONS:l-Serine treatment in patients with 2 different serinesynthesis defects, led to a significant reduction of seizures and an improvement of spasticity, but failed to improve substantially neurocognitive impairment. Therefore, CSF and plasma serine levels should be measured in all cases of severe microcephaly at birth to screen for serine deficiency, as prompt treatment with l-serine may significantly impact the outcome of the disease. Reduced serine levels in fetal cord blood may also be diagnostic as early as 30 weeks of pregnancy.
Authors: Amy Sirr; Russell S Lo; Gareth A Cromie; Adrian C Scott; Julee Ashmead; Mirutse Heyesus; Aimée M Dudley Journal: J Inherit Metab Dis Date: 2020-02-27 Impact factor: 4.982
Authors: Kevin Eade; Marin L Gantner; Joseph A Hostyk; Takayuki Nagasaki; Christian M Metallo; Martin Friedlander; Rando Allikmets; Sarah Giles; Regis Fallon; Sarah Harkins-Perry; Michelle Baldini; Esther W Lim; Lea Scheppke; Michael I Dorrell; Carolyn Cai; Evan H Baugh; Charles J Wolock; Martina Wallace; Rebecca B Berlow; David B Goldstein Journal: Nat Metab Date: 2021-03-22
Authors: Sarah Debs; Carlos R Ferreira; Catherine Groden; H Jeffrey Kim; Kelly A King; Monique C King; Tanya Lehky; Edward W Cowen; Laura H Brown; Melissa Merideth; Carter M Owen; Ellen Macnamara; Camilo Toro; William A Gahl; Ariane Soldatos Journal: Am J Med Genet A Date: 2021-06-04 Impact factor: 2.578
Authors: Amy Sirr; Adrian C Scott; Gareth A Cromie; Catherine L Ludlow; Vida Ahyong; Trey S Morgan; Teresa Gilbert; Aimée M Dudley Journal: G3 (Bethesda) Date: 2018-01-04 Impact factor: 3.154