Deoxyguanosine kinase deficiency: a report of four patients

Özlem Ünal; Burcu Hişmi; Mustafa Kılıç; Hayriye Hızarcıoğlu Gülşen; Turgay Coşkun; Serap Hatice Sivri; Ali Dursun; Aysel Yüce; Ayşegül Tokatlı

doi:10.1515/jpem-2016-0268

Artikel

Deoxyguanosine kinase deficiency: a report of four patients

Özlem Ünal , Burcu Hişmi , Mustafa Kılıç , Hayriye Hızarcıoğlu Gülşen , Turgay Coşkun , Serap Hatice Sivri , Ali Dursun , Aysel Yüce und Ayşegül Tokatlı

Veröffentlicht/Copyright: 11. Mai 2017

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Aus der Zeitschrift Journal of Pediatric Endocrinology and Metabolism Band 30 Heft 6

Abstract

Background:

Hepatic involvement is a common feature in childhood mitochondrial disorders. Deoxyguanosine kinase (DGUOK) deficiency is one of the mitochondrial DNA depletion syndromes associated with hepatocerebral syndrome. Hepatic disease and neurologic dysfunction occurs within weeks after birth. Low birth weight is one of the common features. This study aims to describe the clinical and laboratory features of four infants carrying four different pathogenic variants in the DGUOK gene.

Case presentation:

Common clinical findings were progressive cholestatic liver failure, hypoglycemia, hypotonia and rotatory nystagmus in our DGUOK deficiency patients. Lactic acidosis, elevated serum tyrosine and ferritin levels were the striking laboratory features. Cholestasis, iron deposits, microvesicular steatosis and fibrosis were the histopathological findings seen in liver biopsies of two patients. All patients died with multi-organ failure between the ages of 42 days and 6 months.

Conclusions:

While neurologic findings may occur later in the course of the disease, elevated serum tyrosine levels may alert the physicians to a DGUOK deficiency in a baby with hepatopathy in the presence of the mentioned signs. Early diagnosis is important not only for genetic counseling but also for a possible liver transplantation.

Keywords: elevated tyrosine level; liver failure; mitochondrial diseases; nystagmus

Acknowledgments

The authors thank Linda De Meirleir and Serdar Ceylaner, MD for performing molecular analysis.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2016-7-4

Accepted: 2017-4-3

Published Online: 2017-5-11

Published in Print: 2017-5-24

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https://doi.org/10.1515/jpem-2016-0268

Schlagwörter für diesen Artikel

elevated tyrosine level; liver failure; mitochondrial diseases; nystagmus