Impact of acetazolamide on congenital disorder of glycosylation type 1A: a case report

*Correspondence: [e-mail].

Abstract

Case Presentation: Female patient, 11 months old, presented with delayed motor development. The patient was born at 37 weeks' gestational age as part of a twin pregnancy. At birth, the patient had mild hypotonia, whereas her twin sister was unremarkable. There was no significant family history. Examination revealed little visual attention with nystagmus and generalized hypotonia, particularly axial. She was unable to sit without support, crawl, or roll over with ease, and exhibited impaired fine motor coordination with slight intentional tremors. Normal deep reflexes were present, while the defense (parachute) reflex was absent. In a Denver model evaluation, the patient displayed a developmental delay of approximately four to six months. An electroencephalogram showed normal findings, while a cranial magnetic resonance imaging showed cerebellar hypoplasia and atrophy. Exome sequencing revealed two pathogenic variants of the PMM2 gene, responsible for congenital disorder of glycosylation type 1A inherited in a recessive pattern. The patient underwent cognitive stimulation through the Denver model, as well as speech therapy, occupational therapy, and physiotherapy. Additionally, acetazolamide was initiated. At two years and three months old, the patient had improved in all areas, particularly after starting acetazolamide. However, she still exhibited trunk hypotonia and difficulty with fine motor coordination, although she was able to sit without support and stand with support from a lying position.

Discussion: Congenital disorders of glycosylation are characterized by defective glycosylation of proteins and lipids, which can cause malfunctions in all systems. The most common defect arises from a mutation in the PMM2 gene. The disease has a heterogeneous clinical presentation, with neurological manifestations being the most common, including intellectual disability, cerebellar dysfunction, and hypotonia. Currently, there are few treatment options for this disease, but acetazolamide has been shown to reduce cerebellar dysfunction.

Final Comments: Congenital disorder of glycosylation type 1A is a relatively rare disorder with a poor prognosis, and there are few validated treatment options available. However, this case demonstrates a good response to acetazolamide, which should be used in conjunction with other therapies under study.

Publication History

Article published online:
12 May 2025