Background Hermansky–Pudlak syndrome (HPS) may present to the ophthalmologist with signs suggestive of oculocutaneous albinism. Consideration of HPS as a differential diagnosis is important due to its potential systemic complications. HPS6 is a rarely reported subtype.

Methods Three patients from two families underwent clinical examination, imaging and targeted systemic investigations. Electrophysiology with visual-evoked potentials (VEPs) was performed in both children of family 1. Whole exome sequencing (WES) was performed on the proband of family 1. Bidirectional Sanger sequencing of the single exon and intron–exon boundaries of HPS6 was performed on all affected patients and segregation confirmed in available relatives.

Results Two siblings presented in infancy with nystagmus and reduced vision. They were initially diagnosed with isolated foveal hypoplasia with no aberrant chiasmal misrouting on VEPs. WES performed in the proband when 10 years of age identified a novel homozygous missense variant in HPS6 and further questioning elicited a history of nose bleeds and mild bruising. Segregation supported causality of this variant in the affected younger sibling. In the third unrelated patient, an initial diagnosis of ocular albinism was made at 3 months with HPS only diagnosed at 26 years. Biallelic, truncating mutations in HPS6 were identified by candidate Sanger sequencing and included a novel variant. Abnormal platelet function consistent with HPS was confirmed in all patients.

Conclusions The diagnosis of HPS in all patients was delayed due to a mild systemic phenotype. Next-generation sequencing can aid diagnosis of syndromic conditions with important consequences for preventing morbidity.