Background S-adenosylhomocysteine hydrolase deficiency due to pathologic variants
inAHCYgene is a rare neurometabolic disease for which no eye phenotype has been documented.
Pathologic variants inCRB1gene are known to cause a wide spectrum of autosomal recessive
retinal diseases with Leber's congenital amaurosis as a most common. The aim of this
study is to report co-inheritance of neurometabolic disease and eye disease in a pedigree.
Materials and Methods Comprehensive eye examination was performed in available family
members together with color vision test, visual fields, fundus images, OCT, electroretinogram
and visual evoked potentials. Genetic testing included whole-exome sequencing (WES),
retinal dystrophy gene panel and segregation analysis. Results Two children from a
family not known to be consanguineous were affected with neurometabolic disease and
one of them presented with reduced vision due to maculopathy. The mother had symptoms
of retinal degeneration of unspecified cause. Clinical WES revealed homozygous missense
pathologic variants inAHCYgene c.148G>A, p.(Ala50Thr) as a cause of S-adenosylhomocysteine
hydrolase deficiency. Retinal dystrophy gene panel sequencing revealed two heterozygous
missense pathologic variants inCRB1gene c.1831T>C, p.(Ser611Pro) and c.3955T>C, p.(Phe1319Leu)
in the proband and her mother. These variants segregated with disease phenotype in
family members. Conclusions Establishing an ocular genetic diagnosis may be challenging
with the co-existence of a rare systemic genetic disease with previously unknown eye
involvement. Extensive phenotyping and genotyping of available family members showed
that the proband and her mother shared aCRB1-related retinopathy at different stages
while the brother did not.