First Two Cases of Arginase 1 Deficiency in Slovakia
2Univ.Child.Hosp., Slovakia
6Inst.Hum.Biol.Gen.Clin.,Univ.,Hosp, Slovakia
7Charles Univ., First Fac.Med., Dept.Pediat. and Inher.Met.Dis.,, Czech Republic
Background: Arginase 1 deficiency (ARG1-D) is a very rare disorder with an estimated prevalence of 1:1,000,000. It is more common in Latin America with the lowest population prevalence in European countries. We present the first two cases of ARG1-D in Slovakia.
Case reports
Case 1: The male patient was born to unrelated parents and had a birth weight of 2800 g. His psychomotor development was normal until 5 years old with occasional febrile seizures. At the age of 5 years, his parents noted toe walking, a worsening gait and balance and he experienced his first seizures with a loss of consciousness at 6 years old. An MRI was negative and a biochemical investigation revealed a high plasma level of arginine (446 µmol/L) and ARG1-D was confirmed by enzyme assay. DNA analysis revealed a homozygous 3bp deletion in exon 2 of the ARG1 gene. Despite standard treatment, the progression of spastic diplegia necessitated surgical correction of heel cord contractures (achillotenotomy) in both lower limbs and his plasma arginine levels were 2-3 times the upper reference limit.
Case 2: The male patient was from the physiologic gravidity of parents with low social status. His Apgar score was 9/10 and his birth weight was 3910 g. At the age of 2 and half years, he was admitted to the local hospital with liver dysfunction (higher ALT and AST) and anaemia as suspicion of hepatitis. During hospitalisation, transient loss of consciousness appeared with seizures and mild hyperammonemia (123 µmol/L) and high plasma arginine (496.5 µmol/L), so he received standard therapy of ARG1-D. An MRI revealed periventricular leukomalacia and DNA analysis showed novel homozygous mutation c.703_704 del in exon 7 of the ARG1 gene. At the age of 6, his gait worsened and falling, with spastic paraplegia. The patient died at the age of 15 years.
Conclusion:
The hallmark of the ARG1-D diagnosis in these two patients was spasticity of lower limbs, a transient loss of consciousness and high plasma arginine concentration.
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