The clinical variations and diagnostic challenges of deoxyguanosine kinase deficiency: a descriptive case series

Abstract

Objectives Deoxyguanosine kinase (DGUOK) deficiency is one of the leading causes of the mitochondrial DNA-depletion syndromes (MDDS) associated with hepatocerebral involvement. Herein, we present four cases of DGUOK deficiency to emphasize the clinical variability of disease and the challenges in the diagnosis of DGUOK deficiency. Case presentation Hepatomegaly, hyperlactatemia, elevated alpha fetoprotein (AFP), alanine, and transaminase levels were detected in all patients, and cholestasis, coagulopathy, and hypotonia were common findings. All patients had a low birth weight, one patient underwent liver transplantation (LT). Clinical and laboratory findings of two patients and one patient suggested neonatal hemochromatosis and type 1 tyrosinemia, respectively. All patients were diagnosed with DGUOK deficiency by performing molecular genetic analysis. Conclusions Mitochondrial DNA-depletion syndromes should be kept in mind in cases in which hypotonicity, lactic acidosis, and neonatal cholestasis are observed. DGUOK deficiency may present in different clinics suggesting neonatal hemochromatosis or tyrosinemia type 1.

Considerations for liver transplantation in deoxyguanosine kinase deficiency: A case series and review of the literature

“…Parents should be counseled on the natural history of mitochondrial diseases and the potential for extra‐hepatic manifestations to progress after transplant. In addition to possible worsening of neurologic disease, patients have been reported to develop renal impairment, 5,23 myopathy, 25 pulmonary hypertension, 5,15 and malignancy 2,4,5 following transplantation, and thus require scrupulous follow‐up in the posttransplant period.…”

“…previously summarized transplant outcomes in 20 patients with DGUOK deficiency 7 . Since that time four additional patients have been reported in the literature 13–15 . Analyzing these cases according to the severity of neurologic involvement is informative (Table 2).…”

“…7 Since that time four additional patients have been reported in the literature. [13][14][15] Analyzing these cases according to the severity of neurologic involvement is informative (Table 2).…”

“…18 The 14 patients with DGUOK deficiency and absent or mild neurologic involvement, including hypotonia, had far better outcomes with only one death occurring during the early posttransplant period and three deaths occurring within 2 years after transplant. 7,15,[20][21][22][23] The remaining 10 patients were alive at follow-up intervals from 2 years to 22 years posttransplant with mild neurologic involvement documented in some patients. These studies highlight the significance of utilizing a multidisciplinary approach in making decisions regarding liver transplantation.…”

Hypoglycaemia Metabolic Gene Panel Testing

“…The Alpers-Huttenlocher syndrome is characterized by hepatic involvement with jaundice, cholestasis, hepatomegaly, elevated transaminases, evolving into liver failure with hypoglycemia associated with progressive neurologic symptoms and refractory epilepsy ( 79 ). Patients diagnosed with DGUOK mutations present with low birth weight and in a few weeks manifest neurological signs of rotatory nystagmus, hypotonia, and developmental delay, associated with hypoglycemia, raise of lactate and plasma alanine ( 80 ). SUCLG1 deficiency has a characteristic methylmalonic aciduria at urinary organic acids ( 81 ).…”