Treatable cause for drug-resistant epilepsy; arginase deficiency masquerading as progressive myoclonic epilepsy

Dear Editor,

Arginase deficiency (AD) is a rare recessive metabolic disorder affecting the urea cycle. The disorder usually presents as failure to thrive, developmental delay/regression, spastic diplegia and ataxia.^[1] Here, we present a case of AD presenting as progressive myoclonic epilepsy (PME).

Seven-year-old female child born out of a consanguineously married couple presented with seizures that started at 5 years of age. The developmental delay started at 9 months of age followed by regression with spasticity and ataxia started at 28 months of age. She lost activities of daily living, language and independent walking by 6 years of age. She started having infrequent myoclonic jerks at 5 years of age requiring multiple antiseizure medications (ASMs). She had an aversion to protein-rich foods such as milk. She had significant failure to thrive which started at the age of 28 months. Examination showed weight of 11 kg (<−3 standard deviation [SD]), length of 115 cm (−1 to −2 SD), head circumference of 47 cm (<−3 SD), with BMI <−3 SD, spasticity [Figure 1a and b] and cerebellar signs. Based on the above findings, she was suspected PME. Her complete haemogram, blood gases, ammonia (35.5 μmoL/L) and lactate (19.88 mg/dL) were normal. Magnetic resonance imaging showed diffuse cerebral and cerebellar atrophy [Figure 2a and b] and multifocal epileptiform discharges with secondary generalisation on electroencephalograph [Figure 3]. Tandem mass spectroscopy showed elevated arginine of 330.37 umoL/L. Exome sequencing showed a pathogenic homozygous missense variant, c.428A>G, p.(Gln143Arg) in exon 4, of ARG1 gene. With dietary modifications, and special formula diets, decrease in the number of ASMs, there was a significant improvement in the control of seizures and improvement in the development.

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Figure 1:

(a and b) Clinical photographs of child with scissoring of limbs suggestive of spasticity in the bilateral lower limbs.

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Figure 2:

(a) Sagittal view of magnetic resonance imaging of the brain showing cerebellar atrophy and (b) T2-weighted axial view showing mild periventricular hyperintensities.

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Figure 3:

Electroencephalogram of child showing diffuse slowing with multifocal spikes, sharp waves with secondary generalisation were noted.

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PME manifests as myoclonic jerks, ataxia and neuroregression.^[2] Metabolic disorders presenting as myoclonic jerks are rare.^[3] In AD, seizures are known to occur in 60–75% of cases which are usually treatable with monotherapy.^[1,4] Pavuluri et al. reported Lennox-Gastaut syndrome and developmental epileptic encephalopathy secondary to AD.^[5] The current case of neuroregression, myoclonic jerks, spastic ataxia masquerading as PME which is unusual. To conclude, AD is a treatable disorder and needs to be considered in PME phenotype with failure to thrive, spasticity and ataxia to avoid side effects of ASMs.