IllnessHypoglycemia, ketotic; differential diagnosis

NGS +

[Sanger]

Ketotic hypoglycemia is the most common cause of hypoglycemia presenting under emergency conditions in otherwise healthy children aged 6 months to 6 years. Ketotic hypoglycemia is usually caused by decreased oral intake due to gastrointestinal disturbances with vomiting and/or prolonged fasting. It is likely that affected children cannot tolerate prolonged fasting because of low levels of gluconeogenic amino acids and reduced release of ketone bodies from fat stores. Ketotic hypoglycemia is usually idiopathic and thus a diagnosis of exclusion. In most cases, idiopathic Ketotic hypoglycemia seizes after a few episodes by 6 years of age. Several serious hormonal and metabolic disorders, including cortisol and growth hormone deficiencies and various forms of glycogen storage diseases, may trigger ketotic hypoglycemia. The reasons for one or more such episodes due to inadequate food intake are generally difficult to assess. In any case, given the multiple genetic causes of KH, a gene panel should be designed to detect numerous hormonal and metabolic disorders as well as glycogen storage diseases. The corresponding diagnostic yield is not known. Therefore, a negative molecular genetic result excludes the clinical diagnosis by no means.

Reference: https://doi.org/10.1186/s13633-019-0066-9

• Allelic: Polyglucosan body disease, adult form (GBE1)
• Alpha-methylacetoacetic aciduria (ACAT1)
• Biotinidase deficiency (BTD)
• Congenital disorder of glycosylation, type It (PGM1)
• Diabetes mellitus, noninsulin-dependent (SLC2A2)
• Erythrocyte lactate transporter defect (SLC16A1)
• Fanconi-Bickel syndrome (SLC2A2)
• Fructose intolerance, hereditary (ALDOB)
• Fructose-1,6-bisphosphatase deficiency (FBP1)
• Glycogen storage disease 0, liver (GYS2)
• Glycogen storage disease 0, liver (HLCS)
• Glycogen storage disease IIIa (AGL)
• Glycogen storage disease IIIb (AGL)
• Glycogen storage disease IV (GBE1)
• Glycogen storage disease IXa1 (PHKA2)
• Glycogen storage disease IXa2 (PHKA2)
• Glycogen storage disease IXc (PHKG2)
• Glycogen storage disease Ia (G6PC1)
• Glycogen storage disease Ib (SCL37A4)
• Glycogen storage disease Ic (SCL37A4)
• Glycogen storage disease VI (PYGL)
• Glycogen storage disease XI (LDHA)
• Glycogen storage disease XII (ALDOA)
• Hyperinsulinemic hypoglycemia, familial, 7 (SLC16A1)
• Isovaleric acidemia (IVD)
• Metabolic encephalomyopathic crises, recurr., rhabdomyolysis, cardiac arrhyth., neurodegen. (TANGO2)
• Methylmalonic aciduria, mut(0) type (MUT)
• Methylmalonyl-CoA epimerase deficiency (MCEE)
• Monocarboxylate transporter 1 deficiency (SLC16A1)
• Phosphorylase kinase deficiency of liver + muscle, AR (PHKB)
• Propionicacidemia (PCCA)
• Propionicacidemia (PCCB)
• Pyruvate carboxylase deficiency (PC)
• Renal glucosuria (SLC5A2)
• Succinyl CoA:3-oxoacid CoA transferase deficiency (OXCT1)