1. Adenosine kinase deficiency: Three new cases and diagnostic value of hypermethioninemia
- Author
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Zeynep Demir, Apolline Imbard, Caroline Sevin, Anne Davit-Spraul, Jean-François Benoist, Michal Rozenfeld Bar Lev, Yael Mozer Glassberg, Pauline Gaignard, Abdelhamid Slama, Charlotte Mussini, Dalila Habes, Emmanuel Gonzales, Patrice Thérond, Emmanuel Jacquemin, and Pierre-Hadrien Becker
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Adenosine ,Developmental Disabilities ,Endocrinology, Diabetes and Metabolism ,Mitochondrial disease ,Glycine N-Methyltransferase ,Adenosine kinase ,030105 genetics & heredity ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Liver disease ,0302 clinical medicine ,Endocrinology ,Internal medicine ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Child ,Adenosine Kinase ,Amino Acid Metabolism, Inborn Errors ,Molecular Biology ,Retrospective Studies ,Epilepsy ,Methionine ,biology ,business.industry ,Liver Diseases ,Infant, Newborn ,Infant ,medicine.disease ,ADK ,Mitochondrial respiratory chain ,chemistry ,biology.protein ,Female ,Hypermethioninemia ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Adenosine kinase (ADK) deficiency is characterized by liver disease, dysmorphic features, epilepsy and developmental delay. This defect disrupts the adenosine/AMP futile cycle and interferes with the upstream methionine cycle. We report the clinical, histological and biochemical courses of three ADK children carrying two new mutations and presenting with neonatal cholestasis and neurological disorders. One of them died of liver failure whereas the other two recovered from their liver damage. As the phenotype was consistent with a mitochondrial disorder, we studied liver mitochondrial respiratory chain activities in two patients and revealed a combined defect of several complexes. In addition, we retrospectively analyzed methionine plasma concentration, a hallmark of ADK deficiency, in a cohort of children and showed that methionine level in patients with ADK deficiency was strongly increased compared with patients with other liver diseases. ADK deficiency is a cause of neonatal or early infantile liver disease that may mimic primary mitochondrial disorders. In this context, an elevation of methionine plasma levels over twice the upper limit should not be considered as a nonspecific finding. ADK deficiency induced-liver dysfunction is most often transient, but could be life-threatening.
- Published
- 2021