ATP6AP1‐CDG: Follow‐up and female phenotype

Abstract

In 2016, 11 male patients were reported with immunodeficiency and hepatic, gastric and (in some) neurological disease due to X-linked ATP6AP1 deficiency (ATP6AP1-CDG). In 2018, three other patients were reported with additional features: connective tissue abnormalities, sensorineural hearing loss, hyperopia, glomerular and tubular dysfunction, exocrine pancreatic insufficiency and altered amino acid and lipid metabolism. We here present a followup of three reported siblings showing progression of deafness to total hearing loss, progressive loss of hair up to alopecia, chestnut skin and, at last followup, in some of them proteinuria. Three female carriers showed a normal serum transferrin isoelectrofocusing but in two of them there was a persistent proteinuria. K E Y W O R D SATP6AP1 deficiency, congenital disorder of glycosylation, proteinuria

Congenital disorders of glycosylation: Prevalence, incidence and mutational spectrum in the Polish population

“…In this cohort, 2822 samples were also investigated through collaborative initiatives of EUROGLYCAN (the years 2000–2003, 2822 analyses) and EUROGLYCANET (the years 2005–2009, 6098 analyses). Some of the patients have been previously reported [ [21] , [22] , [23] , [24] , [25] ].…”

Fractionated plasma N‐glycan profiling of novel cohort of ATP6AP1‐CDG subjects identifies phenotypic association

“…Improvement of visceral and cutaneous manifestations has been previously reported in other CDG types 23,35,36 . However, hair loss and SNHL are apparently progressive over time 34 . P8, who is 67 years old at the time of evaluation, has a history of SNHL with onset at age 65, which could be age‐related.…”

“…Heterozygous females are generally asymptomatic and lack the main characteristic manifestations of the disease. The only potential manifestations from heterozygous females described in a single extended pedigree were proteinuria and SNHL (possibly age‐related) in 2/3 and 1/3 carrier mothers, respectively 1,34 . Their glycosylation studies were reported as normal, 34 although fractionated N‐glycan analysis was not performed.…”

“…The reported dysmorphic features (10/30) are variable among the patients and have no consistent pattern ( 9,11,12 and P2, P4, P6, P7, and P10-12). Some features improve with age and include hepatic involvement and cutis laxa 8,9,34 as well as developmental delay (P1, P4, P10, and P11). Improvement of visceral and cutaneous manifestations has been previously reported in other CDG types.…”

“…Some features improve with age and include hepatic involvement and cutis laxa 8,9,34 as well as developmental delay (P1, P4, P10, and P11). Improvement of visceral and cutaneous manifestations has been previously reported in other CDG types 23,35,36 .…”