Perinatal and early infantile symptoms in congenital disorders of glycosylation

Abstract

Congenital disorders of glycosylation (CDG) are a rapidly growing family of inborn errors. Screening for CDG in suspected cases is usually performed in the first year of life by serum transferrin isoelectric focusing or mass spectrometry. Based on the transferrin analysis patients can be biochemically diagnosed with a type 1 or type 2 transferrin pattern, and labeled as CDG-I, or CDG-II. The diagnosis of CDG is frequently delayed due to the highly variable phenotype, some cases showing single organ involvement and others mimicking syndromes, like skeletal dysplasia, cutis laxa syndrome, or congenital muscle dystrophy. The aim of our study was to evaluate perinatal abnormalities and early discriminative symptoms in 58 patients consecutively diagnosed with diverse CDG-subtypes. Neonatal findings and clinical features in the first months of life were studied in 36 children with CDG-I and 22 with CDG-II. Maternal complications were found in five, small for gestational age in nine patients. Five children had abnormal neonatal screening results for hypothyroidism. Congenital microcephaly and neonatal seizures were common in CDG-II. Inverted nipples were uncommon with 5 out of 58 children. Dysmorphic features were mostly nonspecific, except for cutis laxa. Early complications included feeding problems, cardiomyopathy, thrombosis, and bleeding. Cases presenting in the neonatal period had the highest mortality rate. Survival in CDG patients is highly dependent on early intervention therapy. We recommend low threshold screening for glycosylation disorders in infants with neurologic symptoms, even in the absence of abnormal fat distribution. Growth retardation and neonatal bleeding increase suspicion for CDG.

TMEM165 Deficiency: Postnatal Changes in Glycosylation

“…Only children with conspicuous clinical features are selectively screened for CDG. Thus, CDG syndromes are often diagnosed in the first year of life, but normally not within the neonatal period or the first 3 months of life (Funke et al 2013). In the present case, a sibling already diagnosed with TMEM165-CDG allowed prenatal diagnosis.…”

“…Other proteins like a1-antitrypsin were also shown to be normally glycosylated in an affected individual in utero. Other examples for negative IEF screening for different forms of CDG syndrome (PMM2-CDG, ATP6V0A2-CDG, SRDA3-CDG) in the first weeks of life have been reported (Funke et al 2013). Why transferrin IEF is a poor marker neonatally for various CDGs is not entirely clear.…”

Infant with cardiomyopathy: When to suspect inborn errors of metabolism?

“…Several case reports in the literature suggest that CDGs should be considered in infants with cardiomyopathy and multisystem disorders. Infants with CDG Ⅰa (phosphomannomutase 2 deficiency) are have been most often been reported to have hypertrophic cardiomyopathy [12][13][14][15][16] and infants with dolichol kinase deficiency have been reported to have dilated cardiomyopathy [17,18] . Case reports exist for cardiomyopa- Byers SL et al .…”

“…Additional metabolic evaluations were unremarkable, including acylcarnitine profile, urine and plasma amino acids, ammonia, cholesterol, urine and plasma carnitine and creatine kinase. Although the lactate level was normal, pyruvate was slightly low, which caused the lactate/pyruvate ratio to be elevated at 53 (normal [10][11][12][13][14][15][16][17][18][19][20]. Pompe disease was ruled out based on normal enzyme activity.…”

“…November 26, 2014|Volume 6|Issue 11| WJC|www.wjgnet.com thy associated with other CDGs [12,19] . Organic acidurias are the result of enzyme deficiencies characterized by the excretion of specific organic acids in the urine.…”