Identification and molecular analysis of 17 novel variants of hydroxymethylbilane synthase in Chinese patients with acute intermittent porphyria.

A partial deficiency of the heme biosynthetic enzyme hydroxymethylbilane synthase (HMBS) leads to acute intermittent porphyria (AIP), a severe neurovisceral, autosomal dominant disorder with low penetrance. Even though in-depth investigations of the HMBS variants have been carried out by researchers in Britain, France, Russia, and Sweden, this area remains uninvestigated in China owing to the rarity and lack of clinical understanding of the disease. In this study, 78 unrelated AIP patients revealed 48 different HMBS variants, of which 17 were novel. These included 22 missense variants, 9 splicings, 5 nonsense variants, 10 small deletions, 1 repeat insertion, and 1 complex deletion-insertion variant. The variant c.673C > T, found in 10 unrelated patients, was the most frequent variant, followed by the variant c.517C > T, found in 7 unrelated patients. We performed western blotting and immunofluorescence staining with four novel variants (c.653G > A, c.597dupC, c.726-727del, and c.1045_1046delAA) to detect the expression levels of mutant HMBSs. The results showed a variant-mediated decrease in the mutant-HMBS level, suggesting that the variant resulted in impaired gene product functions. Moreover, the in vitro functional verification in this study provided PS3_moderate evidence for American College of Medical Genetics and Genomics (ACMG) to grade the pathogenicity of novel variants in AIP.

Out-of-season spawning of largemouth bass in a controllable recirculating system.

Largemouth bass (LMB) production exceeded 0.7 million tons in 2021 and has become one of the most important freshwater aquaculture species in China. The stable and fixed culture cycle led to regular and drastic price fluctuation during the past decade. Strong price fluctuation provides opportunities and challenges for the LMB industry, and out-of-season spawning (OSS) and culture will provide technical support for the opportunities. To induce OSS at a low cost, we established a controllable recirculating system that allows precise thermo-photoperiod manipulation. In the system, four experimental groups were assigned, 18NP (18°C overwintering water temperature, natural photoperiod), 18CP (18°C overwintering water temperature, controlled photoperiod), 16CP (16°C overwintering water temperature, controlled photoperiod), and NTNP (natural water temperature and natural photoperiod), to determine the effects of chilling temperature and photoperiod on spawning performance. OSS was observed in all the experimental groups without significant differences, except NTNP. The manipulated broodstock can re-spawn 3 months later in the next spring in advance. Further analysis of the volume percentage of different stages of oocytes provides a base for excellent regression between the volume percentage of the primary growth stage, cortical alveoli stage, vitellogenesis/maturation stage, and gonadal development/maturation. The results suggest that the volume percentage of oocytes is a better indicator of gonadal development and maturation than the gonadosomatic index. We also found that LMB prefers palm fiber as a spawning nest over gravel. The findings of this work provide important technique guidance for practical OSS of the LMB aquaculture industry and standardization of ovary development and maturation in fish with asynchronous developmental oocytes.

The challenge of managing comorbidities: a case report of primary Sjogren's syndrome in a patient with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is a rare inherited metabolic disease associated with heme metabolism. Primary Sjogren's syndrome (PSS) is a common autoimmune disease. The combined presence of AIP and PSS complicates treatment. A rare case of concomitant AIP and PSS is reported in this paper. A 30-year-old woman with AIP had recurrent acute abdominal pain, nausea and vomiting, constipation, persistent chest, back, and waist pain, red urine, positivity for porphobilinogen (PBG) in urine and a pathogenic mutation of the HMBS gene. Two and a half years after she was diagnosed with AIP, she was diagnosed with PSS based on dryness of the eyes and mouth, the elevation of immunoglobulins (IgG and IgA) and positive results on an anti-SS-A antibody test, an anti-SS-B antibody test, Schirmer's test and a labial gland biopsy. A mutation in the HMBS gene was detected in the patient and her cousin, but the patient had more severe AIP and more severe symptoms (such as epilepsy and a limp), which may be related to the co-morbidity of PSS. According to her PSS activity score, the patient had an ESSDAI score of 9 and required systemic treatment. However, potential medications were limited by AIP, so mycophenolate mofetil was eventually added to delay the progression of the primary disease.

An extremely rare combination of acute intermittent porphyria and Turner syndrome.

A very rare case of acute intermittent porphyria (AIP) co-existing Turner syndrome (TS) is reported for the first time. A 32-year-old woman was diagnosed with AIP due to recurrent acute abdominal pain, red urine and pathogenic mutation of Hydroxymethyl synthetase (HMBS) gene. At the same time, TS was confirmed by Karyotype analysis results of 46,X,i(X)(q10), which accompanied by primary amenorrhea, elevated serum concentrations of follicle-stimulating hormone (FSH). Since the first attack of AIP, the patient has been increasingly depressed, and Psychiatry identified major depression. Duloxetine was chosen after careful deliberation, and the patient's mood stabilized. AIP had not recurred after half a year. Since sex hormones are the exacerbating factor of acute attack of AIP, sex hormone replacement therapy for TS was not administered. In conclusion, the conditions of AIP co-existing TS are complicate, and the treatment still needs to be improved by multiple disciplines in the follow-up.