ESPE Abstracts (2022) 95 P1-525

1Division of Pediatric Endocrinology, Shaare Zedek Medical Center, Jerusalem, Israel; 2Department of Pediatrics, Shaare Zedek Medical Center, Jerusalem, Israel; 3Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel; 4The Department of Pediatrics, Hadassah Hebrew University Medical Center, Jerusalem, Israel; 5Pediatric Day Care Unit, Schneider children's hospital, Petah Tikva, Israel; 6Departments of Medicine (Medical Genetics) and Genome Sciences, University of Washington, Seattle, USA; 7Division of Pediatric Endocrinology, Hadassah Medical Center, Faculty of Medicine, Hebrew University, Jerusalem, Israel

Background: Phosphoglucomutase 1 (PGM-1) deficiency is a congenital disorder of glycosylation caused by an impairment of glucose-1-phosphate and glucose-6-phosphate interconversion.

The clinical phenotype of PGM1 deficiency is variable and includes several endocrine manifestations such as recurrent hypoglycemia and short stature, which may be associated with the decreased levels of growth hormone (GH), insulin like growth factor-1 (IGF1) and insulin like growth factor-binding protein 3 (IGF-BP3) reported in PGM1 deficiency. The growth response to Growth hormone therapy in PGM1 deficiency has been reported so far only in one single case. GH effect on glucose homeostasis in PGM1 cases was not yet elucidated.

Objectives: To study the growth, IGF-1 axis, and glucose homeostasis in three patients with PGM1 deficiency prior and following GH therapy.

Case Report: Two girls and one boy presented at infancy and early childhood (4 -30 months) with dysmorphic features, short stature and recurrent severe hypoglycemic episodes associated with seizures. Laboratory tests showed evidence of growth hormone insensitivity with normal to high growth hormone response to stimulation tests but low-normal IGF-1 and IGF-BP3. Transferrin electrophoretic pattern was consistent with congenital disorders of glycosylation (CDG). Genetic workup revealed a homozygous mutation (c.112A>T, p.N38Y) in phosphoglucomutase gene at the two female patients and compound heterozygous novel mutations (c.1140insT and c.1348G>T) in the male patient. Two patients were treated with recombinant growth hormone which led to reduction in the hypoglycemic events and increase in growth velocity.

Table 1: Growth hormone axis and growth parameters of the patients
  GH stimulation test response Basal IGF-1 IGF-1 after an IGF-1 stimulation test Height SDS before GH treatment Growth velocity during 1st years of GH treatment
Patient 1a 35 ng/ml 3.72 nmol/l 7.31 nmol/l -2 SDS 7.2 cm/y
Patient 2b   2.72 nmol/l   -3.4 SDS  
Patient 3c 8 ng/ml 6.9 nmol/l 15.1 nmol/l -3.07 SDS 7.47 cm/y
Blank squares- missing data GH doses aPatient 1- 0.04 mg/kg/d.
The treatment was intermittent due to financial issues.
b Patient 2 was not treated with Growth hormone due to parents' refusal.
c Patient 3- 0.033 mg/kg/d.

Conclusions: Growth may be interrupted in PGM1 deficiency, with evidence of interrupted activity of GH. Growth hormone therapy may be beneficial and improve both growth and the dysregulated carbohydrate metabolism.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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