Beneficial outcome of early dietary lysine restriction as an adjunct to pyridoxine therapy in a child with pyridoxine dependant epilepsy due to Antiquitin deficiency

Maina P Kava; Leah Bryant; Peter Rowe; Barry Lewis; Lawrence Greed; Shanti Balasubramaniam

doi:10.1002/jmd2.12121

Beneficial outcome of early dietary lysine restriction as an adjunct to pyridoxine therapy in a child with pyridoxine dependant epilepsy due to Antiquitin deficiency

JIMD Rep. 2020 Apr 13;54(1):9-15. doi: 10.1002/jmd2.12121. eCollection 2020 Jul.

Authors

Maina P Kava^{1

2

3}, Leah Bryant⁴, Peter Rowe^{1

5}, Barry Lewis⁶, Lawrence Greed⁶, Shanti Balasubramaniam^{2

7

8

9}

Affiliations

¹ Department of Neurology Perth Children's Hospital Perth Western Australia Australia.
² Department of Metabolic Medicine and Rheumatology Perth Children's Hospital Perth Western Australia Australia.
³ School of Paediatrics and Child Health University of Western Australia Perth Western Australia Australia.
⁴ Department of Nutrition and Dietetics Perth Children's Hospital Perth Western Australia Australia.
⁵ West Perth Child Development Service Community Health West Perth Western Australia Australia.
⁶ Department of Clinical Biochemistry PathWest Nedlands Western Australia Australia.
⁷ Western Sydney Genetics Program The Children's Hospital at Westmead Sydney New South Wales Australia.
⁸ Discipline of Genetic Medicine, Sydney Medical School University of Sydney Sydney New South Wales Australia.
⁹ Discipline of Child & Adolescent Health, Sydney Medical School University of Sydney Sydney New South Wales Australia.

Abstract

Pyridoxine-dependent epilepsy (PDE) is a potentially treatable vitamin-responsive epileptic encephalopathy. The most prevalent form of PDE is due to an underlying genetic defect in ALDH7A1 encoding Antiquitin (ATQ), an enzyme with α-aminoadipic semialdehyde dehydrogenase (AASADH) activity which facilitates cerebral lysine degradation. Devastating outcomes including intellectual disability and significant developmental delays are still observed in 75% to 80% of pyridoxine responsive individuals with good seizure control, potentially attributable to the accumulation of toxic intermediates α-aminoadipic semialdehyde (AASA) and its cyclic form Δ¹-piperideine-6-carboxylate (P6C) in plasma, urine and CSF. Thus, adjunct treatment strategies incorporating lysine restriction and arginine supplementation, separately or in combination with pyridoxine have been attempted to enhance seizure control and improve cognitive function. We describe a 4 year old girl with classical PDE who demonstrated significant improvements in clinical, neurological and developmental outcomes including absence of clinical seizures and cessation of antiepileptic medications since age 3 months, normalisation of EEG, significant improvement in the white matter signal throughout the cerebrum on neuroimaging and significant reduction in urine P6C and pipecolic acid levels post- combined therapy with lysine restricted diet in conjunction with pyridoxine and folinic acid. Lysine restriction was well tolerated with impressive compliance and plasma lysine levels remained within the lower reference ranges; mean level 70 μmol/L (ref range 52-196 μmol/L). This case further emphasizes the benefit of early dietary intervention as an effective adjunct in the management of PDE.

Keywords: antiquitin; lysine restriction; neurological improvements; pyridoxine‐dependent epilepsy; α‐aminoadipic semialdehyde dehydrogenase.

Publication types

Case Reports