Updated clinical and glycomic features of mannosyl-oligosaccharide glucosidase deficiency: Two case reports

Figure 1 Dysmorphic features and/or radiologic findings in the younger sister (A-L) and elder sister (M-P) at various stages. A: Pneumonia, mediastinal shift towards the right at the age of 1.1 mo; B: Pneumonia on right upper lobe at 1.8 mo; C: Abdominal film at 1.7 mo; D and E: Microcephaly, narrow forehead, hypertelorism, retrognathia, and slightly enlarged tongue; F: Large ear lobe with forward rotation; G: Slight hirsutism with long eyelashes; H: A birthmark; I and J: Overlapped toes; K: Abnormal fat distribution around the external genitalia; D-K: Dysmorphic features of the younger sister at the age of 5.6 mo; L: Pneumonia at 5.7 mo; A-C and L: Progressively enlarged heart size and liver span; M: Chest computed tomography of the elder sister at the age of 2.2 mo; N: Chest and abdominal X-rays at the age of 2.3 mo; O: Chest and abdominal X-rays at the age of 2.8 mo; P: Chest and abdominal X-rays at the age of 3.5 mo; M-O: Pneumonia and progressively enlarged liver span; O: Enlarged heart size. Parental consent was obtained for publication of personal images.

Figure 2 Abnormal glycoforms detected on immunoglobulin G1 in the serum of the younger sister and proposed compensatory pathway in mannosyl-oligosaccharide glucosidase-congenital disorder of glycosylation. A: Representative mass spectrums generated from the younger sister, parents, and pooled healthy controls by nano-electrospray ionization quadrupole time-of-flight mass spectrometry; B: N2 serials of oligosaccharides on immunoglobulin G1 (IgG1) normalized by the control. Abnormal enrichment of N2H10 and N2H5 were detected; C: Fractions of IgG1 with fucosylation, galactosylation, sialylation, mannosylation, and bisection showing significantly high levels mannosylation and sialylation in the patient sample; D: Proposed mannosyl-oligosaccharide glucosidase-independent pathway leading to increased levels of N2H10 and N2H5 (M5) in vivo. N: N-acetylglucosamine and/or N-acetylgalactosamine; H, hexaose (galactose, glucose, or mannose); GANAB: α-Subunit of glucosidase II; PRKCSH: β-Subunit of glucosidase II; MAN1B1: Endoplasmic reticulum mannosyl-oligosaccharide α-1,2-mannosidase; MAN1A, MAN1A2, and MAN1C1: Mannosyl-oligosaccharide α-1,2-mannosidase; MANEA: Endo-alpha-1,2-mannosidase.