Adenosine kinase deficiency with neurodevelopemental delay and recurrent hepatic dysfunction: A case report.

Marjan Shakiba,Fereshteh Rezagholizadeh ,Hassan Fazilaty,Maryam Ziadlou,Arghavan Shakiba,William A Gahl ,Fatemeh Mahjoub,Babak Behnam

doi:10.12715/ard.2014.3.2

Abstract

Hypermethioninemia may be benign, present as a nonspecific sign of nongenetic conditions such as liver failure and prematurity, or a severe, progressive inborn error of metabolism. Genetic causes of hypermethioninemia include mitochondrial depletion syndromes caused by mutations in the MPV17 and DGUOK genes and deficiencies of cystathionine β-synthase, methionine adenosyltransferase types I and III, glycine N-methyltransferase, S-adenosylhomocysteine hydrolase, citrin, fumarylacetoacetate hydrolase, and adenosine kinase. Here we present a 3-year old girl with a history of poor feeding, irritability, respiratory infections, cholestasis, congenital heart disease, neurodevelopmental delay, hypotonia, sparse hair, facial dysmorphisms, liver dysfunction, severe hypermethioninemia and mild homocystinemia. Genetic analysis of the adenosine kinase (ADK) gene revealed a previously unreported variant (c.479–480 GA>TG) resulting in a stop codon (p.E160X) in ADK. A methionine-restricted diet normalized the liver function test results and improved her hypotonia.

Highlights

Hypermethioninemia is a major biochemical sign of certain nongenetic disorders as well as a variety of inborn errors of metabolism
We report an Iranian case of adenosine kinase (ADK) deficiency, with a typical clinical presentation except that the liver disease was more severe and the patient had a neurologic bladder and red cell macrocytosis
After another 3 months, the patient was again admitted with fever, productive cough, irritability and poor feeding She had a seborrheic rash on the scalp and an erythematous rash on the abdomen, as well as buccal candidiasis, a systolic murmur, and hypotonia

Summary

Introduction

Hypermethioninemia is a major biochemical sign of certain nongenetic disorders as well as a variety of inborn errors of metabolism. We report an Iranian case of ADK deficiency, with a typical clinical presentation except that the liver disease was more severe and the patient had a neurologic bladder and red cell macrocytosis. This female child of consanguineous parents was born by cesarean section with a birth weight of 2800 g. The patient was treated with ceftriaxone, discharged on co-amoxiclav, and referred for follow-up liver function tests After another 3 months, the patient was again admitted with fever, productive cough, irritability and poor feeding She had a seborrheic rash on the scalp and an erythematous rash on the abdomen, as well as buccal candidiasis, a systolic murmur, and hypotonia.

Discussion

Conclusions