1 - Serviço de Genética Médica, Centro Hospitalar e Universitário de Lisboa Central, Lisboa, Portugal
2 - Serviço de Neuropediatria, Área de Pediatria Médica, Centro de Referência de Doenças Hereditárias do Metabolismo, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
3 - Unidade de Cuidados Intensivos Neonatais, Centro Hospitalar e Universitário de Lisboa Central, Lisboa, Portugal
- 17th Internacional Symposium of the Portuguese Society for Metabolic Disorders, virtual meeting, 8-10 de Setembro. Sob a forma de poster.
Resumo:
Background: MOGS‐CDG is a congenital disorder of N-linked glycosylation that results from mannosyloligosaccharide glucosidase (MOGS) deficiency. MOGS is expressed in the endoplasmic reticulum and plays a critical role in processing N-glycans by removing the distal α‐1,2‐linked glucose from the Glc3Man9GlcNAc2 oligosaccharide precursor. Recessive mutations in MOGS gene are responsible for multisystemic manifestations with prominent central nervous system (CNS) involvement, microcephaly, typical dysmorphisms, immunological dysfunction, respiratory difficulty, and other abnormalities (cardiac, gastrointestinal, ophthalmological, and endocrine). Only 11 cases were reported so far with poor prognosis (most with life span of less than a year).
Case Report: We report a neonate female with a polymalformative syndrome. Second child of non‐consanguineous healthy parents with no relevant familial medical history. Prenatal findings included fetal growth restriction, retrognathia, short femur, non‐specific changes in fetal MRI and normal array. The patient was born at 39 weeks with respiratory distress that required mechanical ventilation and was transferred to the neonatal intensive care unit. At our observation she showed generalized hypotonia, feeding problems, microcephaly, dysmorphisms (low hairline, low set ears, short palpebral fissures, corneal opacity, deviated nasal septum, bulbous nasal tip, cleft palate, retrognathia, clenched hands with overlapping fingers, metatarsus adductus and anterior anus). MRI showed extensive CNS malformations and EEG abnormal activity. Echocardiogram revealed an interventricular communication and abdominal imaging identified hepatomegaly. Absence of peristalsis since birth led to abdominal distension and a laparotomy was performed with a poor outcome. She died at 40 days old. Exome sequencing identified two variants in MOGS gene, a truncating likely pathogenic variant c.882del (p.(Glu295Asnfs*10)) and a missense variant of uncertain significance c.2225A>G (p.(Asn742Ser)). Parental segregation confirmed that the variants were in trans and with reverse phenotype provided a diagnosis for this patient and family.
Comments: CDG should be included in the differential diagnosis of any multisystemic congenital abnormalities. Our patient’s phenotype showed many overlapping features with the previous reported MOGS‐CDG cases. Only exome sequencing provided an explanation for the clinical findings and allowed genetic counselling to the family.
Palavras Chave: Congenital disorders of N-linked glycosylation, mannosyl‐oligosaccharide glucosidase deficiency, MOGS‐CDG, multisystemic abnormalities