Case report of holocarboxylase synthetase deficiency (late-onset) in 2 Chinese patients

RATIONALE: Holocarboxylase synthetase (HCLS) deficiency, especially the late-onset type, is a rare disease. Affected patients can present with irreversible metabolic acidosis and may be misdiagnosed with a glucose metabolic disorder. Prompt and correct diagnosis and treatment can reduce mortality to a great extent. PATIENT CONCERNS: We report 2 Chinese patients who were diagnosed with late-onset HCLS deficiency. The age of onset of the 2 patients was approximately 8 months. The 2 patients had skin lesions, severe profound metabolic acidosis, dyspnea, and hyperglycemia. DIAGNOSES: The results of urinary and blood organic acid analysis with gas chromatography/mass spectrometry revealed multiple carboxylase deficiency. Maple syrup urine disease and diabetic ketoacidosis could not be excluded. This finding is different from those of hypoglycemic complications reported in previous reports. Human genetic analysis eventually provided a definite diagnosis. INTERVENTIONS: Prompt oral treatment with biotin dramatically corrected the metabolic imbalances of the 2 patients, and continued oral biotin therapy was essential to the improvement of their prognoses. OUTCOMES: Their metabolic disorders were corrected within 48 hours. During long-term follow-up, the patients achieved developmental milestones. LESSONS: Late-onset HCLS deficiency may present with obvious hyperglycemia. Human genetic analysis eventually provided a definite diagnosis. Prompt treatment with biotin is vital to correct metabolic imbalances, and continued therapy is essential to the improving long-term prognoses. Their mutations were p.R508W and c.1088T > A, and these mutations might represent hot-spot genes in Chinese populations with HCLS deficiency. The variants c.1484T > G(p.L495∗) and c.835G > T(p.E279x) are likely pathogenic, and more studies are needed to confirm these results.