First reported adult patient with retinal dystrophy and leukodystrophy caused by a novel ACBD5 variant: A case report and review of literature

To date, eight publications have reported on 16 patients with ACBD5 deficiency.

“To date, eight publications have reported on 16 patients with ACBD5 deficiency”

Cognitive symptoms in RDLKD range from mild learning difficulties to severe deficits in speech and comprehension.

“The cognitive symptoms ranged from mild learning difficulties (Al Shamsi et al., 2025) to severe deficits in speech and comprehension (Bartlett et al., 2021).”

Delayed language development was reported in five ACBD5-deficient patients.

“and delayed language development in five (Ferdinandusse et al., 2017; Bartlett et al., 2021; Gorukmez et al., 2022; Hasturk et al., 2024; Al Shamsi et al., 2025; Supplementary Table 1).”

Cerebral atrophy with dilatation of the sulci and ventricles on MRI scans was observed in only two ACBD5-deficient patients.

“However, cerebral atrophy—with dilatation of the sulci and ventricles on MRI scans—was observed in only two patients (Bartlett et al., 2021; Rudaks et al., 2024; Supplementary Table 1), indicating that widespread grey matter degeneration is potentially relatively rare.”

Cognitive impairments were reported in six ACBD5-deficient patients.

“Beyond motor and sensory deficits, cognitive impairments were reported in six patients (Ferdinandusse et al., 2017; Bartlett et al., 2021; Rudaks et al., 2024; Al Shamsi et al., 2025), and delayed language development in five (Ferdinandusse et al., 2017; Bartlett et al., 2021; Gorukmez et al., 2022; Hasturk et al., 2024; Al Shamsi et al., 2025; Supplementary Table 1).”

All 14 reported patients exhibited reduced psychomotor abilities, which progressed to a complete inability to walk in the following years.

“All 14 reported patients exhibited reduced psychomotor abilities, which progressed to a complete inability to walk in the following years”

Rod-cone or cone-rod dystrophies affecting both photoreceptor types were described in at least nine patients.

“Rod-cone or cone-rod dystrophies, affecting both photoreceptor types, were described in at least nine patients”

One reported RDLKD patient received autologous intrathecal hematopoietic stem cell transplantation at age 29, leading to transient, partial improvement of vision, speech, and locomotor abilities.

“One of the reported RDLKD patients received an autologous intrathecal hematopoietic stem cell transplantation at the age of 29, which lead to a transient, partial improvement of vision, speech and locomotor abilities (Bartlett et al., 2021).”

Other features of ataxia, dysarthria, cleft palate, facial dysmorphisms, progressive microcephaly, and seizures are reported sporadically in ACBD5-related retinal dystrophy with leukodystrophy.

“Other features of ataxia, dysarthria, cleft palate, facial dysmorphisms, progressive microcephaly, and seizures are reported sporadically (Abu-Safieh et al., 2013;Bartlett et al., 2021;Ferdinandusse et al., 2017;Gorukmez et al., 2022).”

Early motor development was normal in this case, but can be variable, with both normal and delayed milestones reported in other cases.

“Early motor development was normal in our case, but can be variable, with both normal and delayed milestones reported in other cases (Abu-Safieh et al., 2013;Bartlett et al., 2021;Ferdinandusse et al., 2017;Gorukmez et al., 2022).”

Based on the findings of this case and the other reported adult case, progressive dysarthria, urinary dysfunction, and cognitive decline appear to develop as patients enter adulthood.

“Based on the findings of our case and the other reported adult case, progressive dysarthria, urinary dysfunction, and cognitive decline appear to develop as patients enter adulthood.”

Only seven cases of ACBD5-related retinal dystrophy with leukodystrophy have been reported to date, including one other case diagnosed in adulthood.

“Only seven cases of ACBD5-related retinal dystrophy have been reported in the literature to date, including one other case diagnosed in adulthood.”

Rod-cone dystrophy, delayed or regression of motor development, progressive cognitive decline, and imaging features of a progressive leukodystrophy are common features of ACBD5-related retinal dystrophy with leukodystrophy.

“Rod-cone dystrophy, delayed or regression of motor development, progressive cognitive decline, and imaging features of a progressive leukodystrophy are common features (Abu-Safieh et al., 2013;Bartlett et al., 2021;Ferdinandusse et al., 2017;Gorukmez et al., 2022).”

This ovarian insufficiency feature was not reported in the one other published adult case, who was female.

“This feature was not reported in the one other published adult case, who was female (Bartlett et al., 2021).”