ESPE Abstracts (2018) 89 P-P3-190

Clinical and Molecular Genetic Characterization of Two Patients due to Mutations

Yu Dinga, Niu Lia, Guoying Changa, Juan Lia, Ruen Yaoa, Yiping Shenb, Jian Wanga, Xiaodong Huanga & Xiumin Wanga

aShanghai Children’s Medical Center, Shanghai, China; bBoston Children’s Hospital, Boston, USA

Background: The Phosphoglucomutase 1 (PGM1) enzyme plays a central role in glucose homeostasis by catalyzing the inter-conversion of glucose 1-phosphate and glucose 6-phosphate. Recently, PGM1 deficiency was recognized to cause the congenital disorders of glycosylation (CDGs). PGM1 deficiency is a rare, autosomal recessive inherited disease which can cause the extreme variability of clinical symptoms multi-organ dysfunction, including ketotic hypoglycemia, dilated cardiomyopathy, cleft palate, growth retardation, and hepatopathy.

Methods: The present study describes the clinical features of two Chinese Han pediatric patients who presented with recurrent hypoglycemia, hepatopathy and growth retardation. Patients’ medical histories were recorded. Blood biochemical indices, oral glucose tolerance test, continuous glucose monitoring, hormonal assays, echocardiography, abdomen ultrasound, and brain MRI scan were performed and analyzed. Targeted gene sequencing (TGS) using the Agilent SureSelect XT Inherited Disease Panel was performed to screen for causal genetic variants, and the relevant mutations identified by TGS were verified by Sanger sequencing in the patients and their parents.

Results: Serum electrolyte and thyroid hormones levels were within normal ranges in both patients. They did not have dilated cardiomyopathy. The subscore in the patients according to the Tulane PGM1-CDG Rating Scale (TPCRS) was 4(patient 1) and 8(patient 2). In patient 1, an abdominal ultrasound demonstrated mild hepatic steatosis, while a brain magnetic resonance imaging (MRI) scan demonstrated that the pituitary was slightly thinning. Patient 1 did not have cleft palate. Patient 2 presented with cleft palate and micrognathia. Her cortisol levels during hypoglycemia was low. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were prolonged slightly. Here, DNA sequencing identified three variations of the PGM1 gene (NM_002633.2) in the two patients. Patient 1 had a novel homozygous mutation (c.119delT, p.Ile40Thrfs*28) in exon 1. In patient 2, we found a compound heterozygous mutations of c.1172G>T(p.Gly391Val) (novel) and c.1507C>T(p.Arg503*) (known pathogenic).

Conclusions: This report deepens our understanding of the clinical features of PGM1 mutation. The early molecular genetic and multisystem assessment was essential to provide the timely and proper treatment.

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