A Study of Endocrine, Metabolic, and Genetic Risk Factors of Pediatric Persistent Hypoglycemia at Sohag University Hospital

NCT07533318 | Not Yet Recruiting

• 1 other identifier: Soh-Med--26-3-2MD
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Glucose is the key metabolic substrate for tissue energy production. In the perinatal period, the mother supplies glucose to the fetus, and for most of the gestational period, the normal lower limit of fetal glucose concentration is around 54 mg/dl (3 mmol/L)(1). During the first 24-48 hours of life, as normal neonates transition from intrauterine to extrauterine life, their plasma glucose (PG) concentrations are typically lower than later in life (2). Distinguishing between transitional neonatal glucose regulation in normal newborns and hypoglycemia that persists or occurs for the first time beyond the first 3 days of life is important for prompt diagnosis and effective treatment to avoid serious consequences, including seizures and permanent brain injury (2) The definition of hypoglycemia remains controversial in neonates and children. Some approaches define hypoglycemia on the basis of symptoms, others on the PG value. According to the American Academy of Pediatrics (AAP) and Pediatric Endocrine Society (PES), hypoglycemia is diagnosed when plasma glucose is, respectively, \<47 mg/dL and \<50 mg/dL in at term newborns during the first 48 h of life. Different threshold values have been proposed for pre-term infants (3,4) . In at-term newborns after the first 48 h of life, infants and younger children, hypoglycemia is defined when plasma glucose is \<50 mg/dL. This threshold value is low enough to avoid false-positive results, but is unlikely to lead to permanent neurological damage. In older children, it is possible to use Whipple's triad characterized by signs and/or symptoms of hypoglycemia, reduced plasma glucose concentration and resolution of these signs/symptoms after acquisition of normoglycemic status(3,4). Per the AAP guidelines, if it is not possible to maintain a glucose concentration \>45 mg/dL after 24 hours with using a glucose infusion rate (GIR) rate of 5-8 mg/kg/min, consideration should be given to the possibility of a disorder causing persistent hypoglycemia (5,6) Also, Persistent hypoglycemia (PH) beyond 3 days of life warrants investigation. (7) Blood glucose concentrations are maintained within this range by a complex interplay of hormones that control glucose production and utilization. The key hormones that regulate glucose homeostasis include insulin, glucagon, epinephrine, norepinephrine, cortisol, and growth hormone. Pathological endocrine and metabolic conditions that affect either glucose production or utilization can lead to hypoglycemia (8) The most common causes of hypoglycemia in children are diabetes and idiopathic ketotic hypoglycemia. Hypoglycemia also occurs in other endocrine disorders and inborn errors of metabolism (IEMs). In most cases, hypoglycemia is due to increased usage of glucose (hyperinsulinism, fatty acid oxidation disorders (FAODs), sepsis), decreased nutritional supply (gastroenteritis), or decreased endogenous production of glucose (adrenal insufficiency, IEMs, liver failure) (8). The primary endocrine cause of persistent neonatal hypoglycemia is hyperinsulinism (HI), where dysregulated insulin secretion suppresses ketone production and deprives the brain of alternative fuels. HI can be genetic, such as mutations in the KATP channel genes, or acquired due to perinatal stress factors like intrauterine growth restriction. Hormone deficiencies, including hypopituitarism with cortisol and growth hormone deficiency, can also present with hypoglycemia in the newborn period (4). Metabolic disorders causing hypoglycemia include fatty acid oxidation disorders, which prevent fat breakdown and result in hypoketotic hypoglycemia with potential liver or cardiac involvement. Glycogen storage diseases impair glucose release from glycogen stores and gluconeogenesis, leading to severe fasting hypoglycemia accompanied by elevated lactate and hepatomegaly. Disorders of gluconeogenesis similarly disrupt the liver's ability to convert substrates like alanine and glycerol into glucose (4). Genetic causes of hypoglycemia in children include monogenic defects such as mutations in ABCC8 and KCNJ11 causing congenital hyperinsulinism, as well as genes involved in glycogen storage diseases (e.g., G6PC, PYGL), gluconeogenesis (e.g., FBP1), and hormonal regulation (e.g., GLUD1, HNF4A). Advances in next- generation sequencing have enabled the identification of both common and rare genetic etiologies, improving diagnostic accuracy and personalized management (4). Retrospective studies suggest the rate of undiagnosed endocrine or metabolic disorders in pediatric patients with recurrent hypoglycemia is as high as 8-28% (9,10) In our study, we will use a stepwise approach to help early and accurate diagnosis of endocrine, metabolic, and suspected genetic causes of persistent hypoglycemiaamong children at Sohag University Hospital.

Conditions

Hypoglycaemia

Outcome Measures

Primary Outcomes (1)

• Diagnosis of neonates, infants, and children with endocrine, metabolic, and suspected genetic causes of persistent hypoglycemia at Sohag University Hospital.

  2 years

Eligibility Criteria

• Age: 1 Day - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

All patients from birth up to 18 years of life, presented with persistent and recurrent hypoglycemia, will be included in the study

You may qualify if:

• All patients from birth up to 18 years of life who presented with persistent and recurrent hypoglycemia, will be included in the study Persistent hypoglycemia (PH) is that persist beyond 3 days or Per the AAP guidelines, if it is not possible to maintain a glucose concentration \>45 mg/dL after 24 hours with using a GIR rate of 5-8 mg/kg/min (5,6) Recurrent hypoglycemia is the occurrence of more than 2 episodes of low blood sugar, often associated with symptomatic neuroglycopenia.

You may not qualify if:

• Transient hypoglycemia:e.g Neonate:e.g
• Infant of a diabetic mother
• Prematurity
• Intra-uterine growth retardation
• Perinatal stress ( infection/sepsis, asphyxia, hypothermia, and respiratory distress)
• Maternal beta blocker use Infant and Childhood:e.g
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• Malnutrition (marasmus or kwashiorkor)
• Illness ( gastroenteritis, vomiting, or diarrhea leading to inadequate intake )
• Prolonged exercise/fasting
• Diabetic patient on insulin therapy
• Medications/ toxins: accidental ingestion of diabetes medication, alcohol, or aspirin
• Factitious hypoglycemia

Sponsors & Collaborators

• Sohag University: lead

Study Sites (1)

Pediatric department, Sohag University Hospital

Sohag, Sohag Governorate, 82524, Egypt

Location

Related Publications (8)

• Rosenfeld E, Alzahrani O, De Leon DD. Undiagnosed hypoglycaemia disorders in children detected when hypoglycaemia occurs in the setting of illness: a retrospective study. BMJ Paediatr Open. 2023 Feb;7(1):e001842. doi: 10.1136/bmjpo-2022-001842.

  PMID: 36759017 BACKGROUND

• White K, Truong L, Aaron K, Mushtaq N, Thornton PS. The Incidence and Etiology of Previously Undiagnosed Hypoglycemic Disorders in the Emergency Department. Pediatr Emerg Care. 2020 Jul;36(7):322-326. doi: 10.1097/PEC.0000000000001634.

  PMID: 30365409 BACKGROUND

• Ghosh A, Banerjee I, Morris AAM. Recognition, assessment and management of hypoglycaemia in childhood. Arch Dis Child. 2016 Jun;101(6):575-580. doi: 10.1136/archdischild-2015-308337. Epub 2015 Dec 30.

  PMID: 26718813 BACKGROUND

• Mehta S, Brar PC. Severe, persistent neonatal hypoglycemia as a presenting feature in patients with congenital hypopituitarism: a review of our case series. J Pediatr Endocrinol Metab. 2019 Jul 26;32(7):767-774. doi: 10.1515/jpem-2019-0075.

  PMID: 31211689 BACKGROUND

• Committee on Fetus and Newborn; Adamkin DH. Postnatal glucose homeostasis in late-preterm and term infants. Pediatrics. 2011 Mar;127(3):575-9. doi: 10.1542/peds.2010-3851. Epub 2011 Feb 28.

  PMID: 21357346 BACKGROUND

• Quarta A, Iannucci D, Guarino M, Blasetti A, Chiarelli F. Hypoglycemia in Children: Major Endocrine-Metabolic Causes and Novel Therapeutic Perspectives. Nutrients. 2023 Aug 11;15(16):3544. doi: 10.3390/nu15163544.

  PMID: 37630734 BACKGROUND

• Thornton PS, Stanley CA, De Leon DD, Harris D, Haymond MW, Hussain K, Levitsky LL, Murad MH, Rozance PJ, Simmons RA, Sperling MA, Weinstein DA, White NH, Wolfsdorf JI; Pediatric Endocrine Society. Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children. J Pediatr. 2015 Aug;167(2):238-45. doi: 10.1016/j.jpeds.2015.03.057. Epub 2015 May 6. No abstract available.

  PMID: 25957977 BACKGROUND

• Guemes M, Rahman SA, Hussain K. What is a normal blood glucose? Arch Dis Child. 2016 Jun;101(6):569-574. doi: 10.1136/archdischild-2015-308336. Epub 2015 Sep 14.

  PMID: 26369574 BACKGROUND

MeSH Terms

Conditions

Hypoglycemia

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Menatalla Moamen Ramadan Mohamed

CONTACT

+201062475212; menaamoamen@med.sohag.edu.eg

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant lecturer of pediatrics

Study Record Dates

• First Submitted: April 9, 2026
• First Posted: April 16, 2026
• Study Start: April 15, 2026
• Primary Completion (Estimated): January 15, 2028
• Study Completion (Estimated): April 15, 2028
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

EG (1)