Adenosine Kinase Deficiency: A Rare and Treatable Condition

Adenosine kinase (ADK) deficiency manifests with seizures, global developmental delay, and distinctive facial features. Fewer than 30 cases have been reported globally – none from India. 

A nine-month-old girlwas evaluated for fever, encephalopathy, seizures, and hepatomegaly. The child was born to consanguineous parents. 

On examination, she had elevated liver enzymes – alanine aminotransferase (ALT) – 1,210 U/Land aspartate aminotransferase (AST) at 553 U/L. She was managed conservatively. 

At 11 months, she was readmitted with similar symptoms, including fever and jaundice. Tandem mass spectroscopy showed elevated methionine (729 µMol/L) and homocysteine (47 µMol/L), with normal Vitamin B12 levels. An MRI of the brain revealed diffuse white matter changes with marked diffusion restriction – corresponding signal drop on ADC mapping. 

Her developmental milestones were delayed, with a developmental quotient (DQ) of 20 at 3 years and 6 months. Examination at this age showed normal growth parameters, frontal bossing, mongoloid slant, broad nasal bridge, hypopigmented sparse hair, generalized hypotonia, and brisk reflexes. Exome sequencing with copy number analysis identified a novel likely pathogenic 48 kb homozygous deletion involving exons 1-3 of the ADK gene. 

Starting a methionine-restricted diet significantly improved her development, raising her DQ to 45, and she experienced no recurrence of seizures.

This case shows global developmental delay, seizures, liver involvement, and elevated methionine and homocysteine levels in a pediatric patient. Given the hypermethioninemia, deficiencies in methionine adenosyl transferase III and glycine N-methyltransferase were considered but ruled out due to the severe neurological involvement. The absence of lens dislocation and marfanoid features ruled out cystathionine beta-synthase deficiency. 

Although low methionine diets and liver transplants improvehepatic dysfunction in ADK deficiency patients, neurological improvements have been limited. Therefore, in any child presenting with hypermethioninemia, neurological, and hepatic symptoms, ADK deficiency should be considered.

Source: Gowda VK, Babu S, Kinhal U, et al. Indian Journal of Pediatrics. 2024 Jun 17:1-.