18º Congresso Brasileiro de Neurologia Infantil

Dados do Trabalho



Apresentação do caso

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 symptom of HLD.


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.

Comentários finais

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.

Referências (se houver)

Rakotomamonjy J, Rylaarsdam L, Guemez-Gamboa A. PYRC2-Related Hypomyelinating Leukodystrophy: More to This Than Meets the Eye. Neuron. 2020 Jul 8;107(1):3-5. doi: 10.1016/j.neuron.2020.06.007. PMID: 32645307.
Srivastava P, Mishra AK, Sarkar N. PYCR2 Mutation Causing Hypomyelination and Microcephaly in an Indian Child. Cureus. 2021 Apr 24;13(4):e14661. doi: 10.7759/cureus.14661. PMID: 34055512; PMCID: PMC8143271.
Yan H, Ji H, Kubisiak T, Wu Y, Xiao J, Gu Q, Yang Y, Xie H, Ji T, Gao K, Li D, Xiong H, Shi Z, Li M, Zhang Y, Duan R, Bao X, Jiang Y, Burmeister M, Wang J. Genetic analysis of 20 patients with hypomyelinating leukodystrophy by trio-based whole-exome sequencing. J Hum Genet. 2021 Aug;66(8):761-768. doi: 10.1038/s10038-020-00896-5. Epub 2021 Feb 18. PMID: 33597727; PMCID: PMC8310791.
Meng L, Donti T, Xia F, Niu Z, Al Shamsi A, Hertecant J, Al-Jasmi F, Gibson JB, Nagakura H, Zhang J, He W, Eng C, Yang Y, Elsea SH. Homozygous variants in pyrroline-5-carboxylate reductase 2 (PYCR2) in patients with progressive microcephaly and hypomyelinating leukodystrophy. Am J Med Genet A. 2017 Feb;173(2):460-470. doi: 10.1002/ajmg.a.38049. Epub 2016 Nov 11. PMID: 27860360.
Torii T, Shirai R, Kiminami R, Nishino S, Sato T, Sawaguchi S, Fukushima N, Seki Y, Miyamoto Y, Yamauchi J. Hypomyelinating Leukodystrophy 10 (HLD10)-Associated Mutations of PYCR2 Form Large Size Mitochondria, Inhibiting Oligodendroglial Cell Morphological Differentiation. Neurol Int. 2022 Dec 16;14(4):1062-1080. doi: 10.3390/neurolint14040085. PMID: 36548190; PMCID: PMC9787162.
van der Knaap MS, Bugiani M. Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms. Acta Neuropathol. 2017 Sep;134(3):351-382. doi: 10.1007/s00401-017-1739-1. Epub 2017 Jun 21. PMID: 28638987; PMCID: PMC5563342.

Palavras Chave

Hypomielinating Leukodystrophy 10, failure to thrive, PYCR2 gene

Fonte de Fomento (se houver)

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IPPMG- UFRJ - Rio de Janeiro - Brasil


Maria Lina Giacomino de Almeida Passos Azevedo, Aline Chacon Pereira, Amanda Regina Farias Teixeira, Fernanda dos Santos Ribeiro, Jessica Kayene Souza Ferreira, Maria Mariana Muniz Jorge de Melo, Patrícia Selestrini, Sarah Falcão Brasileiro Henriques, Sofia Russi