2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Hypoglycemia as an Initial Presentation of Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE) Syndrome

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This document describes a case of hypoglycemia as the initial presentation of Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE) Syndrome. MNGIE is a mitochondrial DNA depletion syndrome inherited in an autosomal recessive manner, caused by mutations in the TYMP gene. It is characterized by gastrointestinal dysmotility, cachexia, dysphagia, vomiting, diarrhea, and intestinal blockage. The disease typically presents in childhood and is characterized by progressive neurologic and gastrointestinal symptoms, with a mean life expectancy of 36 years.<br /><br />The case involves a 7-month-old male who presented to the emergency department with fever and vomiting. Initial glucose levels were low at 27 mg/dL, and further laboratory tests showed anion gap metabolic acidosis, elevated serum beta-hydroxybutyrate, ketonuria, transaminitis, and increased hepatic echogenicity. The patient had a noncontributory medical history and physical exam, and there was no family history of consanguinity. At 14 months of age, the patient experienced ketotic hypoglycemia and acute liver failure.<br /><br />Further evaluation included molecular testing, which initially did not provide a diagnosis. However, rapid whole genome sequencing revealed homozygosity for a pathogenic variant in the TYMP gene, confirming a diagnosis of MNGIE.<br /><br />This case is significant because it is the first known report of hypoglycemia as an initial and recurrent feature of MNGIE. The pathophysiology of hypoglycemia in MNGIE is unknown but has been observed in other mitochondrial disorders. Therefore, healthcare providers should consider MNGIE in children presenting with progressive gastrointestinal and/or neurological symptoms, along with episodic ketotic hypoglycemia.<br /><br />The document concludes by highlighting the importance of monitoring patients with MNGIE for hypoglycemia, especially during intercurrent illness, and providing appropriate treatment to prevent further neurological damage. Additionally, the evaluation for MNGIE should include assessment for hepatopathy, ophthalmoplegia, peripheral neuropathy, and asymptomatic leukoencephalopathy.

Asset Subtitle

Presenting Author - Kiri E. Sunde, MD; Co-Author - Amanda B. Pritchard, MD;

Meta Tag

Biochemical genetics

Gastrointestinal System

Metabolic Disorder

Mitochondria

Co-Author Amanda B. Pritchard, MD

Presenting Author Kiri E. Sunde, MD

Keywords

Hypoglycemia

Mitochondrial Neurogastrointestinal Encephalopathy Syndrome

MNGIE

TYMP gene

Autosomal recessive inheritance

Gastrointestinal dysmotility

Cachexia

Dysphagia

Vomiting

Diarrhea