Recognizable phenotypes in CDG

Abstract

Pattern recognition, using a group of characteristic, or discriminating features, is a powerful tool in metabolic diagnostic. A classic example of this approach is used in biochemical analysis of urine organic acid analysis, where the reporting depends more on the correlation of pertinent positive and negative findings, rather than on the absolute values of specific markers. Similar uses of pattern recognition in the field of biochemical genetics include the interpretation of data obtained by metabolomics, like glycomics, where a recognizable pattern or the presence of a specific glycan sub-fraction can lead to the direct diagnosis of certain types of congenital disorders of glycosylation. Another indispensable tool is the use of clinical pattern recognition-or syndromology-relying on careful phenotyping. While genomics might uncover variants not essential in the final clinical expression of disease, and metabolomics could point to a mixture of primary but also secondary changes in biochemical pathways, phenomics describes the clinically relevant manifestations and the full expression of the disease. In the current review we apply phenomics to the field of congenital disorders of glycosylation, focusing on recognizable differentiating findings in glycosylation disorders, characteristic dysmorphic features and malformations in PMM2-CDG, and overlapping patterns among the currently known glycosylation disorders based on their pathophysiological basis.

From gestalt to gene: early predictive dysmorphic features of PMM2-CDG

“…The frequencies of DFs in our sample are similar to those reported 34. Although lipodystrophy is a well-known early indicator of PMM2-CDG, its prevalence is scarcely detailed in previous papers.…”

Clinical and molecular diagnosis of non‐phosphomannomutase 2 N‐linked congenital disorders of glycosylation in Spain

“…The spectrum of clinical findings of this cohort of patients was very wide as typically described in CDG, in whom nearly any organ or system can be affected, particularly the brain. Symptoms can appear at any age; prenatal abnormalities were prevalent in the present series of patients.…”

“…1 The impact of aberrant N-glycosylation, along with the broad range of functions in which affected N-glycosylated proteins are involved, is revealed by the wide clinical spectrum of patients with CDG. 2 These phenotypically diverse disorders typically affect multiple systems including the central nervous, 3 muscular, 4 immune, 5 hematological, 6 and endocrine systems. 7 Serum transferrin isofocusing (IEF) is the standard method for screening of N-glycosylation disorders with sialic acid deficiency.…”

Mutations in the translocon‐associated protein complex subunit SSR3 cause a novel congenital disorder of glycosylation

“…Congenital disorders of glycosylation (CDG) are a group of clinically complex metabolic disorders that frequently present with varying degrees of neurological impairments and, depending on the specific type, can have further organ system involvement. 1,2 To date more than 130 unique disorders have been described covering nearly all known glycosylation pathways with most involving defects in the N-linked glycosylation pathway. 1,3,4 A useful and often reliable biomarker for detecting N-linked related CDG's is the abundant serum glycoprotein, transferrin.…”

“…1,2 To date more than 130 unique disorders have been described covering nearly all known glycosylation pathways with most involving defects in the N-linked glycosylation pathway. 1,3,4 A useful and often reliable biomarker for detecting N-linked related CDG's is the abundant serum glycoprotein, transferrin. 5,6 Often referred to as carbohydrate-deficient transferrin (CDT), an abnormal transferrin profile is frequently designated as a type I or type II, which can indicate the specific portion of the affected pathway, but usually not the specific defective protein.…”