BACKGROUND Hyperprolinemia type 2 (HPII) is a rare autosomal recessive disorder of the proline metabolism, that affects the ALDH4A1 gene. So far only four different pathogenic mutations are known. The manifestation is mostly in neonatal age, in early infancy or early childhood. CASE PRESENTATION The 64-years female patient had a long history of abdominal pain, and episode of an acute neuritis. Ten years later she was admitted into the neurological intensive-care-unit with acute abdominal pain, multiple generalized epileptic seizures, a vertical gaze palsy accompanied by extensive lactic acidosis in serum 26.0 mmol/l (reference: 0.55-2.2 mmol/l) and CSF 12.01 mmol/l (reference: 1.12-2.47 mmol/l). Due to repeated epileptic seizures and secondary complications a long-term sedation with a ventilation therapy over 20 days was administered. A diagnostic work-up revealed up to 400-times increased prolin-level in urine CSF and blood. Furthermore, a low vitamin-B6 serum value was found, consistent with a HPII causing secondary pyridoxine deficiency and seizures. The ALDH4A1 gene sequencing confirmed two previously unknown compound heterozygous variants (ALDH4A1 gene (NM_003748.3) Intron 1: c.62 + 1G > A - heterozygous and ALDH4A1 gene (NM_003748.3) Exon 5 c.349G > C, p.(Asp117His) - heterozygous). Under high-dose vitamin-B6 therapy no further seizures occurred. CONCLUSION We describe two novel ALDH4A1-variants in an adult patient with hyperprolinemia type II causing secondary pyridoxine deficiency and seizures. Severe and potentially life-threatening course of this treatable disease emphasizes the importance of diagnostic vigilance and thorough laboratory work-up including gene analysis even in cases with atypical late manifestation.

中文翻译：

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II型迟发性高蛋白血症患者的新型变异：癫痫持续状态和乳酸性酸中毒的诊断关键。

背景2型高蛋白血症（HPII）是脯氨酸代谢的罕见常染色体隐性遗传疾病，其影响ALDH4A1基因。迄今为止，仅已知四种不同的致病突变。该表现主要发生在新生儿期，婴儿期或幼儿期。病例介绍这位64岁的女性患者有悠久的腹痛史，并患有急性神经炎。十年后，她因急性腹痛，多次全身性癫痫发作，垂直注视麻痹并伴有广泛乳酸性酸中毒，血清26.0 mmol / l（参考值：0.55-2.2 mmol / l）被送进神经重症监护病房，并且CSF 12.01 mmol / l（参考：1.12-2.47 mmol / l）。由于反复发作的癫痫发作和继发性并发症，需要通气疗法进行20天以上的长期镇静。诊断检查显示，尿中脑脊液和血液中脯氨酸水平最多可提高400倍。此外，发现低的维生素B6血清值，与导致继发性吡ido醇缺乏和癫痫发作的HPII一致。ALDH4A1基因测序确认了两个以前未知的化合物杂合变异体（ALDH4A1基因（NM_003748.3）内含子1：c.62 + 1G> A-杂合子和ALDH4A1基因（NM_003748.3）外显子5 c.349G> C，p。（ （Asp117His）-杂合的）。在大剂量维生素B6治疗下，未再发生癫痫发作。结论我们描述了在II型高脯氨酸血症的成年患者中引起继发性吡ido醇缺乏和癫痫发作的两个新的ALDH4A1变体。