Difficult Management of Glucose Homeostasis in a 21-Month-Old Child With Type 1 Diabetes and Unknown Glutaric Aciduria Type I: A Case Report

A 21-month-old boy with previously diagnosed type 1 diabetes was admitted to our unit, presenting with glycometabolic failure (pH 7.30; base excess 211.9 mmol/L; blood glucose 17.3 mmol/L; HbA 1c 10.4% [90 mmol/mol]; glycosuria; and ketonuria). During physical examination he was dehydrated and pale and presented with axial hypotonia with hyposthenia, poor head control, hypo-tonic legs, and hyporeflexia. His neuro-logical clinical status became compromised after the diagnosis of type 1 diabetes when he was 15 months old. During hospitalization , the management of blood glucose ho-meostasis was difficult because of a high level of glycemic variability. Hypo-and hyperglycemic episodes were associated with acute encephalopathic crises characterized by hypotonia, dyskinetic movements, difficulty swallowing, and episodes of opisthotonus with no loss of consciousness. For better control of blood glucose, subcutaneous insulin treatment was stopped (he was being treated with a basal-bolus scheme using rapid and long-acting insulin analogs) and intravenous insulin was started; a sensor was positioned for continuous glucose monitoring. This therapy improved his clinical status and reduced the glucose variability and the number of encephalopathic crises. On the basis of the clinical characteristics , mitochondrial encephalopathy was suspected. The patient underwent several biochemical (creatine kinase, creatine phosphokinase, antinuclear and anti-extractable nuclear antigens antibodies) and instrumental (electroencephalogra-phy and electromyography) examinations , with no pathological results. Urinary organic acids and lactic acid were measured ; muscular biopsy and brain magnetic resonance imaging were performed. Histo-logical examination found a myopathy with accumulation of lipids. The analysis of urinary organic acids revealed high levels of glutaric acid and 3-hydroxyglutaric acid. T2-weighted and fluid-attenuated inversion recovery magnetic resonance images of the brain showed white matter signal abnormalities in different regions (primarily in the posterior periventricular and peritrigonal regions) and a bilateral striatal system (caudate nuclei and puta-mina), as typically happens in glutaric aciduria type I (GA-I) (Fig. 1). GA-I is an autosomal recessive neuro-metabolic disorder (1–3). It is caused by mutations in the glutaryl-CoA dehydro-genase gene localized on chromosome 19p13.2. Glutaryl-CoA dehydrogenase is a key mitochondrial enzyme in the catabolic pathways of the amino acids L-tryptophan and L-lysine (4). Biochemically , GA-I is characterized by an accumulation of glutaric acid and 3-hydroxyglutaric acid, which can be detected in body fluids (plasma, urine) and tissues. Intracellular accumulation of glutaric acid may cause direct mitochondrial toxicity within neu-rons and the disruption of the Krebs cycle. It is clinically characterized by a peculiar neurological presentation. Acute encephalopathic crises …