Glycogen storage disease type IX and growth hormone deficiency presenting as severe ketotic hypoglycemia

Juanita K. Hodax 1 , Serife Uysal 1 , Jose Bernardo Quintos 1 , and Chanika Phornphutkul 2
  • 1 Division of Pediatric Endocrinology, Rhode Island Hospital and Alpert Medical School of Brown University, Providence, RI, USA
  • 2 Division of Human Genetics, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, 593 Eddy Street POB 234, Providence, RI 02903, USA
Juanita K. Hodax, Serife Uysal, Jose Bernardo Quintos and Chanika Phornphutkul

Abstract

Background:

Glycogen storage disease (GSD) type IX and growth hormone (GH) deficiency cause ketotic hypoglycemia via different mechanisms and are not known to be associated. We describe a patient presenting with severe ketotic hypoglycemia found to have both GSD IX and isolated GH deficiency.

Case presentation:

A 3-year-and-11-month-old boy with a history of prematurity, autism, developmental delay, seizures, and feeding difficulty was admitted for poor weight gain and symptomatic hypoglycemia. He was nondysmorphic, with a height of 93.8 cm (2%, –1.97 SDS), and has no hepatomegaly. He developed symptomatic hypoglycemia, with a serum glucose level of 37 mg/dL after 14 h of fasting challenge. Critical sample showed a GH of 0.24 ng/mL. GH provocative stimulation testing was done with a peak GH of 2.8 ng/mL. Brain magnetic resonance imaging showed a hypoplastic pituitary gland. Given the clinical symptoms, suspicion for mitochondrial disease was high. Dual Genome Panel by Massively Parallel Sequencing revealed a hemizygous variant c.721A>G (p1241V) in the X-linked PHKA2 gene, a causative gene for GSD IX. Red blood cell PhK enzyme activity testing was low, supporting the diagnosis.

Conclusions:

Given the patient’s developmental delays that were not explained by GH deficiency alone, further investigation showed two unrelated conditions resulting in deranged metabolic adaptation to fasting leading to severe hypoglycemia.

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