Congenital Disorder of Glycosylation (CDG) Presenting as Non-immune Hydrops Fetalis

Abstract

To the Editor: Non-immune hydrops fetalis (NIHF) is caused by a variety of disorders recently classified in over 6000 individuals. The main causes are cardiovascular disorders (21 %), anemia (10 %), chromosomal and metabolic inborn errors of metabolism (IEM) disorders (20 %); however in 20–25 % of NIHF cases, the cause remains unexplained [1]. Among IEM cases, only 15 cases of congenital disorder of glycosylation (CDG) presenting with NIHF have been reported [2]. We report here a case of NIHF which was later found to be associated with CDG and its various progressive multisystem manifestations. A 34 wk preterm, antenatally diagnosed case of hydrops fetalis was delivered because of fetal distress. She was managed as per the protocol and investigated for possible causes of hydrops fetalis (HF). Immunemediated cause was ruled out with detailed investigations. Echocardiography was normal. USG abdomen showed moderate ascites which resolved within 2 wk. No obvious malformations or dysmorphism were noticed. Second week of life screening showed evidence of congenital hypothyroidism with normal total T4 (11.6 μg/dl), low free T4 (0.5 ng/L) and an elevated thyroid stimulating hormone (TSH 47.8mIU/L). TSH level was normalized over 4 wk with thyroxine treatment. As per few earlier reports, association of NIHF with congenital hypothyroidism was suspected and monitoring and follow up were planned [3]. During next 6 mo she developed recurrent pericardial effusion with no specific etiology. She also developed seizures and generalized hypotonia, failure to thrive, hepatosplenomegaly and coarse facial features. CT chest and abdomen showed pericardial effusion, hepatomegaly with fatty infiltration and bilateral enlarged kidneys. Metabolic workup and urinary glycosaminoglycans (GAG) were normal. Congenital disorders of glycosylation was suspected and isoelectric focusing (IEF) of serum transferrin was done that suggested diagnosis of CDG-Ia, but over next 3 d she died due to massive pericardial effusion and cardio respiratory arrest (Fig. 1). Genetic testing of the parents or child could not be done; however literature suggests CDG type-Ia (PMM2) as the most frequent form of CGD which is caused by deficiency of phosphor manno mutase (PMM) enzyme and associated with mutations in the PMM2 gene located on chromosome 16p13 [4].