关键词: PSAT1基因, 轻型丝氨酸缺乏症, 鱼鳞病合并周围神经病

Abstract:

Objective To investigate the clinical classification, genetic basis, and diagnostic and treatment strategies for serine deficiency caused by PSAT1 gene variants, in order to improve clinical recognition of this disorder. Methods Clinical data were retrospectively collected from a pediatric patient presenting with ichthyosis complicated by peripheral neuropathy. Family-based whole exome sequencing, Sanger validation, and protein structure prediction were performed. Following identification of the causative gene, treatment and follow-up were conducted. A systematic literature review was also carried out to summarize the clinical phenotypes, genetic variant characteristics, treatment responses, and prognostic features. Results The patient was a 12-year-old female who developed dry, scaly skin across the body at 2 years of age. Since the age of 7 years, she experienced progressive weakness in both lower limbs, foot drop, and horizontal nystagmus. Previous examinations revealed normal plasma serine levels (233.29 μmol/L and 319.19 μmol/L). Family-based whole exome sequencing identified a novel homozygous PSAT1 gene variant, c.697C>A (p.Q233K), which was classified as a variant of uncertain significance according to ACMG guidelines. Sanger sequencing confirmed that both parents were carriers. The patient received oral supplementation with L-serine （300 mg·kg^-1·d^-1） and glycine （200 mg·kg^-1·d^-1）. After one week of treatment, the dry skin and desquamation improved significantly. After 13 weeks, gait showed marked improvement, and the patient was able to squat and stand up independently. A literature review identified five additional cases of mild serine deficiency. Including the present case, a total of six cases were identified, all of which carried PSAT1 gene variants. Conclusion The phenotypic spectrum of serine deficiency is broad, with the mild form characterized by childhood-onset ichthyosis and adolescent-onset peripheral neuropathy as core manifestations. Affected individuals often have normal or only mildly reduced plasma serine levels, making this condition highly prone to being missed. Early diagnosis and timely supplementation with L-serine are critical for improving prognosis and can prevent irreversible neurological damage. For patients presenting with unexplained ichthyosis accompanied by peripheral neuropathy, genetic testing should be pursued as early as possible to establish a definitive diagnosis.

Key words: PSAT1 gene, mild serine deficiency disorders, ichthyosis combined with peripheral neuropathy