Nonimmune hydrops fetalis and congenital disorders of glycosylation: A systematic literature review

• Published in: Journal of inherited metabolic disease 2020-03, Vol.43 (2), p.223-233
• Main Authors: Makhamreh, Mona M., Cottingham, Naiga, Ferreira, Carlos R., Berger, Seth, Al‐Kouatly, Huda B.
• Format: Article
• Language: English
• Subjects: Atrophy; Cardiomyopathy; Cerebellum; Congenital diseases; congenital disorders of glycosylation; Differential diagnosis; Edema; Fetuses; Genetic screening; Glycosylation; Hydrops fetalis; Infants; Isoelectric focusing; Literature reviews; Neonates; nonimmune hydrops fetalis; Pregnancy; Prenatal diagnosis; Prognosis; Thrombocytopenia; Transferrin
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1002/jimd.12162

Numerous etiologies may lead to nonimmune hydrops fetalis (NIHF) including congenital disorders of glycosylation (CDG). Recognition of CDG in NIHF is challenging. This study reviews prenatal and neonatal characteristics of CDG presenting with NIHF. A systematic literature search was performed. Thirteen articles met the inclusion criteria. Twenty‐one cases with NIHF associated with a CDG were reported. There were 17 live births, three pregnancy terminations, and one fetal demise. Timing of CDG diagnosis was reported mostly postnatally (90%; 10/11). Postnatal genetic testing was reported in 18 patients; three patients were diagnosed by isoelectric focusing of serum transferrin that showed a type 1 pattern. The genes reported for CDG with NIHF for 15 distinct families include: PMM2 in 47% (7/15), ALG9 in 20% (3/15), ALG8 in 13% (2/15), ALG1 in 7% (1/15), MGAT2 in 7% (1/15), and COG6 7% (1/15). In our review, 81% (17/21) reported facial dysmorphism, 52% (11/21) reported CNS abnormalities, most commonly cerebellar atrophy (64%; 7/11), and 38% (8/21) reported cardiovascular abnormalities, most commonly hypertrophic cardiomyopathy (63%; 5/8). Among live births, 71% (12/17) infants died at a median age of 34 days (range 1‐185). Thrombocytopenia was reported in 53% (9/17) patients. Of those who survived past the neonatal period, 80% (4/5) had significant reported developmental delays. CDG should be on the differential diagnosis of NIHF in the presence of cerebellar atrophy, hypertrophic cardiomyopathy, or thrombocytopenia. Our review highlights the poor prognosis in infants with NIHF due to CDG and demonstrates the importance of identifying these disorders prenatally to guide providers in their counseling with families regarding pregnancy management. Synopsis Poor prognosis in fetuses and infants with nonimmune hydrops fetalis due to congenital disorders of glycosylation highlights the importance of prenatal diagnosis of this disorder.