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The long-term treatment of a patient with type 1 diabetes mellitus and glutaric aciduria type 1: the effect of insulin

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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.

Conclusion: 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

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Abbreviations

CGM:

Continuous glucose monitoring

GA1:

Glutaric aciduria type 1

GCDH:

Glutaryl-CoA dehydrogenase

IEM:

Inborn error of metabolism

ISPAD:

International Society for Pediatric and Adolescent Diabetes

T1DM:

Type 1 diabetes mellitus

T2DM:

Type 2 diabetes mellitus

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Author notes

    Authors and Affiliations

    1. Division of Metabolic Diseases, Department of Woman and Child Health, University Hospital of Padua, Padua, Italy

      Monica Del Rizzo, Andrea Celato, Francesca Furlan, Laura Giordano, Chiara Cazzorla, Ilaria Fasan & Alberto B. Burlina

    2. Diabetology Unit, Department of Woman and Child Health, University Hospital of Padua, Padua, Italy

      Alfonso Galderisi & Carlo Moretti

    3. Human Genetics, Medical University Innsbruck, Innsbruck, Austria

      Johannes Zschocke

    Authors
    1. Monica Del Rizzo
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    2. Alfonso Galderisi
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    3. Andrea Celato
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    4. Francesca Furlan
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    5. Laura Giordano
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    6. Chiara Cazzorla
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    7. Ilaria Fasan
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    8. Carlo Moretti
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    9. Johannes Zschocke
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    10. Alberto B. Burlina
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    Corresponding author

    Correspondence to Alberto B. Burlina.

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    Funding

    This work was supported by Centro Regionale Malattie Metaboliche Ereditarie, Regione Veneto, Italy, and by Associazione Studio Malattie Metaboliche Ereditarie (A.S.M.M.E). The content of the article has not been influenced by the sponsors.

    Conflict of interest

    The authors declare that they have no competing interests.

    Informed consent

    Informed consent was obtained from the family of the patient.

    Authors’ contribution

    MDR is responsible for the treatment of the patient, collecting data, and writing the manuscript. AG is responsible for the treatment of the patient, collecting data, and writing the manuscript. AC is responsible for the treatment of the patient and revising the manuscript. FF is responsible for the treatment of the patient and commenting on the manuscript draft. LG is responsible for the treatment of the patient, collecting data, and commenting on the manuscript draft. CC is responsible for the treatment of the patient and commenting on the manuscript draft. IF is responsible for the treatment of the patient, interpretation of data, and commenting on the manuscript draft. CM for supervising treatment. JK for genetic analysis. AB for supervising treatment, interpretation of data and revising the manuscript.

    Additional information

    Communicated by Mario Bianchetti

    Monica Del Rizzo and Alfonso Galderisi contributed equally to this work.

    Revisions received: 18 November 2015; 13 January 2016

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    Cite this article

    Del Rizzo, M., Galderisi, A., Celato, A. et al. The long-term treatment of a patient with type 1 diabetes mellitus and glutaric aciduria type 1: the effect of insulin. Eur J Pediatr 175, 1123–1128 (2016). https://doi.org/10.1007/s00431-016-2699-5

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    • DOI: https://doi.org/10.1007/s00431-016-2699-5

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