BACKGROUND: Hermansky-Pudlak Syndrome (HPS) is a rare autosomal recessive genetic disorder associated with varied clinical manifestations, including oculocutaneous albinism, bleeding tendency, and systemic complications. Early and accurate diagnosis is crucial for medical interventions and genetic counseling. We aimed to characterize the prevalence and spectrum of pathogenic variants of HPS in the Chinese population through genetic screening of newborns.
METHODS: Genetic screening for HPS mutations was conducted in 29,622 Chinese newborns from 13 provinces using next-generation sequencing. Pathogenic variants were identified and classified according to ACMG guidelines. Prevalence rates were estimated, and potential hotspot variants were identified.
RESULTS: Among screened newborns, 215 carriers with 103 distinct pathogenic variants were identified, including two carriers with additional missense variants. Potential hotspot variants in seven genes were identified, collectively representing over 20 % of carriers in each respective gene. Particularly, the HPS3 c.1838C>G variant was exclusively reported in the Chinese population, suggesting a potential founder effect. The estimated prevalence rate of HPS in China was 2.84/1,000,000.
CONCLUSIONS: Our study provides valuable insights into the genetic landscape of HPS in the Chinese population, aiding in genetic counseling, early diagnosis, and management strategies. These findings contribute to enhancing the understanding and management of HPS in China.

Next-generation sequencing is increasingly applied during the diagnostic work-up of patients with bleeding diathesis and has facilitated the diagnosis of rare bleeding disorders such as inherited platelet function disorders. Mutations in RAS guanyl releasing protein 2 (RasGRP2), also known as calcium- and diacylglycerol-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), underlie a recently described platelet signal transduction abnormality. Here we present the case of a consanguineous family originating from Afghanistan with two siblings affected by recurrent severe mucocutaneous bleedings. Platelet function testing demonstrated a marked reduction of aggregation induced by collagen and adenosine diphosphate. Whole exome sequencing revealed a novel homozygous nonsense RASGRP2 mutation segregating with the bleeding disorder in the family.

Vitamin C deficiency may be common in third-world countries due to malnutrition, but it is currently rare in the USA. Initially, nonspecific symptoms like exhaustion and depression may make this disease difficult to diagnose until classical dermatological manifestations appear. Diagnosis mainly relies on clinical presentation, dietary history to identify risk factors, and dramatic recession of symptoms and signs following vitamin C therapy. Human beings cannot synthesize vitamin C and hence need 90% of vitamin C intake from fruits and vegetables. As a processed carbohydrate-rich diet becomes the staple food, scurvy must be recognized before it becomes potentially fatal. We describe a 65-year-old man with dyspnea, fatigue, anemia, and bleeding diathesis from scurvy and emphasize the importance of dietary history and the critical role of vitamin C in diagnosis and management of this forgotten entity.