title: The long-term treatment of a patient with type 1 diabetes mellitus and glutaric aciduria type 1: the effect of insulin.
abstract: The coexistence of two diseases associated with different metabolic disorders is a very rare event. Some associations, although sporadic, can be particularly challenging both in terms of diagnostic and therapeutic management and in terms of theoretical perspective. Here, we report a child affected by type 1 diabetes mellitus (T1DM) and glutaric aciduria type 1 (GA1). The child was diagnosed with classical T1DM at 15 months of age, with a tendency toward hypoglycemia. A few months later, during an acute intercurrent infective episode, the child displayed acute hypotonia of the lower limbs and limbs dystonia. A brain MRI showed bilateral striatal necrosis, suggesting GA1 diagnosis. Treatment with a low-lysine dietary regimen and carnitine supplementation was started and resulted in an improvement in metabolic control and a reduction of hypoglycemic episodes along with an increasing in insulin daily dose. After 2 years, the neurological outcome consisted of a reduction in dystonic movements and a metabolic stability of both diseases.
  
  
  CONCLUSIONS
  This case provides some insight into the reciprocal interconnections between the two metabolic disorders. Similar pathogenic mechanisms responsible for the neuronal injury might have impacted each other, and a strict relationship between a specific aspect of GA1-impaired metabolism and glucose homeostasis might explain how the tailored management of GA1 was not only effective in controlling the disease, but it also resulted in an improvement in the control of the glycemic profile. What in known: • Glutaric aciduria type 1 (GA1) usually presents in childhood with severe and possibly irreversible neuronal damage, triggered by a catabolic stress • The association of GA1 with other diseases, including type 1 diabetes mellitus (T1DM), is a rare event, complicating the treatment management What is new: • Insulin treatment has a role in preventing GA1 metabolic decompensation, even in the catabolic condition of hypoglycemia • Promoting GA1 metabolic equilibrium by tailoring drug and dietary treatment in our patient affect by T1DM has a positive impact also in improving glycemic balance.
authors: Division of Metabolic Diseases, Department of Woman and Child Health, University Hospital of Padua, Padua, Italy.
authors: Monica
authors: M
authors: Del Rizzo
authors: Diabetology Unit, Department of Woman and Child Health, University Hospital of Padua, Padua, Italy.
authors: Alfonso
authors: A
authors: Galderisi
authors: Division of Metabolic Diseases, Department of Woman and Child Health, University Hospital of Padua, Padua, Italy.
authors: Andrea
authors: A
authors: Celato
authors: Division of Metabolic Diseases, Department of Woman and Child Health, University Hospital of Padua, Padua, Italy.
authors: Francesca
authors: F
authors: Furlan
authors: Division of Metabolic Diseases, Department of Woman and Child Health, University Hospital of Padua, Padua, Italy.
authors: Laura
authors: L
authors: Giordano
authors: Division of Metabolic Diseases, Department of Woman and Child Health, University Hospital of Padua, Padua, Italy.
authors: Chiara
authors: C
authors: Cazzorla
authors: Division of Metabolic Diseases, Department of Woman and Child Health, University Hospital of Padua, Padua, Italy.
authors: Ilaria
authors: I
authors: Fasan
authors: Diabetology Unit, Department of Woman and Child Health, University Hospital of Padua, Padua, Italy.
authors: Carlo
authors: C
authors: Moretti
authors: Human Genetics, Medical University Innsbruck, Innsbruck, Austria.
authors: Johannes
authors: J
authors: Zschocke
authors: Division of Metabolic Diseases, Department of Woman and Child Health, University Hospital of Padua, Padua, Italy. alberto.burlina@unipd.it.
authors: Alberto B
authors: AB
authors: Burlina
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D001921:Brain / Q000000981:diagnostic imaging; D001928:Brain Diseases, Metabolic / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000628:therapy*; D004421:Dystonia / Q000209:etiology; D050770:Glutaryl-CoA Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D006943:Hyperglycemia / Q000628:therapy*; D007223:Infant; D007328:Insulin / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male
chemical_list: D007328:Insulin; D050770:Glutaryl-CoA Dehydrogenase
keywords: Glutaric acid 3-hydroxyglutaric acid; Glutaric aciduria type 1; Glutaryl-CoA dehydrogenase; Insulin treatment dystonia; Type 1 diabetes mellitus