Late-onset Pompe’s disease in children: case report and genetic particularities
Year: 2024
Type: conference-abstract
Abstract: Case presentation: Male, 9 years old, started walking after 2 years of age, at the age of six, he progressively presented global muscle weakness and difficulty walking. Similar family history was denied. Neurological examination: mild facial biparesis, hypophonia, weak cough, global hypotonia, grade 4- proximal strength in the upper limbs and grade 3 in the lower limbs, grade 4+ distal strength in all limbs, strength deficit when standing up in the supine position, reflexes hypoactive and anserine gait. He also presented thoracic kyphosis, hypotrophy of the abdominal muscles, winged scapula, and slight atrophy of the shoulder and pelvic girdles. Electroneuromyography revealed myopathy. CPK dosage was 692 U/L. Complete sequencing of the GAA gene found the presence, in heterozygosity, of the variants described as chr17:80.118.209 CCA>C (2501_2502del];p.[?(;)Thr834Argfs*49]) and Chr17:80.104.542 T>G (NM_000152.5(GAA):c.[-32- 13T>G]), both classified as pathogenic, in the GAA gene, associated with alpha-glucosidase deficiency (OMIM: 232300), autosomal recessive inheritance. The acid alpha-glucosidase dosage was 0.52 mcmol/L/h, with normal being greater than or equal to 2.10 mcmol/L/h. Transthoracic echocardiogram and spirometry were normal. Pompe Disease was diagnosed and he has been receiving an infusion of 12 vials containing 50mg of alpha-glucosidase, every 15 days for a year, undergoing motor physiotherapy. He has improved trunk strength, can stand up without supine support, strength grade of 4+ overall. Currently, he rides a bicycle. Discussion: The infantile form affects children in the first months of life, with cardiomyopathy, hypotonia, and rapidly progressive muscle weakness, and progresses to death within the first year of life. Late-onset disease can manifest between the first year and the sixth decade of life. Typically the late form does not present severe cardiomyopathy and disease progression is slower. Muscle weakness predominates in the proximal muscles with significant impairment of the lower limbs, resulting in impairment in carrying out daily activities, as seen in the reported case. The c.-32-13T>G variant is the most common GAA mutation associated with the childhood/adult phenotype. Almost 90% of patients affected by this phenotype carry this mutation on at least one allele. The chr17:80,118,209 CCA>C variant is quite rare, being present in heterozygosity in 2 of approximately 125 thousand individuals in the world population. Both pathogenic. Final comments: Pompe disease described is possibly caused by these two heterozygous variants in the GAA gene. The relevance of this case demonstrates that the disease started early, at least after 18 months, with a very slow progression and affecting the trunk muscles and that one year of enzyme replacement brought a lot of independence to this child. We also emphasize the Compound Heterozygous Mutations and rarity of the chr17:80.118.209 CCA>C variant, found in this patient.
Source: Arquivos de Neuro-Psiquiatria
DOI: 10.5327/cbn241024
Authors: Maria Luiza Vasconcelos Montenegro, Patrícia Trindade de Lucena, João Eudes Magalhães, Fabíola Lys de Medeiros
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $200
OpenAlex ID: W4416629101