Hypomielinating leukodystrophy 10: a case report

*Correspondence: [e-mail].

Abstract

Case Presentation: This report is about a 7-year-old boy with a homozygous mutation in the PYCR2 gene, who was initially evaluated by paediatric nutrologist due to failure to thrive and recurrent vomiting since his fifth week of life. He was hospitalized from 6 to 12 months of age for nutritional care and a gastrostomy for tube feeding was performed 6 months after discharge. He had his first seizure one week after the procedure, and he had his neurological assessment shortly after. Phenobarbital was prescribed to control the seizures and later, valproic acid, but was quickly discontinued. Carbamazepine and clobazam were needed for seizure control in follow-up evaluations. In recent physical examination, the patient had muscular hypotrophy, spasticity, brisk tendon reflexes, extensor plantar reflexes and minimal interaction with the environment. He also exhibited dysmorphic features such as an elongated face, dysplastic ears, long and smooth philtrum and turricephaly. The electroencephalograms were unspecific. The brain magnetic resonance imaging at the age of three years old revealed accentuation of Sylvian fissures, delayed myelination/hypomyelination, marked diffuse thinning of the corpus callosum and dilation of the supratentorial ventricular system. The patient has a healthy brother sharing the same progenitors and two sisters who do not share the same father nor show any symptoms of HLD.

Discussion: Hypomielinating Leukodystrophy (HLD) is a group of diseases with a heterogeneous genotype but similar phenotypes. It is characterized by a persistent deficit of myelination on MRI scans, affected motor ability and variable intellectual disability. Hypomielinating Leukodystrophy-10 is caused by mutations in PYCR2, a gene that encodes a mitochondrial enzyme involved in proline synthesis. Inheritance pattern is autosomal recessive. This genetic defect manifests with profound intellectual disability, progressive microcephaly, dystonia, and poor overall growth.

Final Comments: The database on HDL-10 is limited and a worse neurodevelopmental outcome has been reported compared to other types of HLD. The reported case shares clinical features with other cases, and the patient has been followed by support therapies. The family received genetic counselling.

 

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Publication History

Article published online:
12 May 2025