青少年起病的成人型糖尿病（MODY）是一类特殊类型糖尿病。MODY10是其中一种较为罕见的类型，与胰岛素基因突变导致胰岛素的合成和分泌障碍有关，大多呈常染色体显性遗传，家族成员中可有不同的临床表现。本文报道1个以低钾性周期性麻痹为主要表现、经全外显子基因检测证实为胰岛素基因突变的MODY10家系，拟通过该病例的诊治体会并结合国内外文献复习，提高临床医生对该特殊类型糖尿病的认识。.

Dominant mutations in CACNA1S gene mainly causes hypokalemic periodic paralysis (PP)(hypoPP). A 68-year-old male proband developed a progressive proximal weakness from the age of 35. Muscle biopsy showed atrophic fibers with vacuoles containing tubular aggregates. Exome sequencing revealed a heterozygous p.R528H (c.1583G>A) mutation in the CACNA1S gene. CACNA1S-related HypoPP evolving to persistent myopathy in late adulthood is a well-known clinical condition. However, isolated progressive myopathy (without PP) was only exceptionally reported and never with an early onset. Reporting a case of early onset CACNA1S-related myopathy in a patient with no HypoPP we intend to alert clinicians to consider it in the differential diagnosis of younger adult-onset myopathies especially when featuring vacuolar changes.

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BACKGROUND: Primary periodic paralysis (PPP) is an inherited disorders of ion channel dysfunction characterized by recurrent episodes of flaccid muscle weakness, which can classified as hypokalemic (HypoPP), normokalemic (NormoPP), or hyperkalemic (HyperPP) according to the potassium level during the paralytic attacks. However, PPP is charactered by remarkable clinical and genetic heterogeneity, and the diagnosis of suspected patients is based on the characteristic clinical presentation then confirmed by genetic testing. At present, there are only limited cohort studies on PPP in the Chinese population.
RESULTS: We included 37 patients with a clinical diagnosis of PPP. Eleven (29.7%) patients were tested using a specific gene panel and 26 (70.3%) by the whole-exome sequencing (WES). Twenty-two cases had a genetic variant identified, representing a diagnostic rate of 59.5% (22/37). All the identified mutations were either in the SCN4A or the CACNA1S gene. The overall detection rate was comparable between the panel (54.5%: 6/11) and WES (61.5%: 16/26). The remaining patients unresolved through panel sequencing were further analyzed by WES, without the detection of any mutation. The novel atypical splicing variant c.2020-5G > A affects the normal splicing of the SCN4A mRNA, which was confirmed by minigene splicing assay. Among 21 patients with HypoPP, 15 patients were classified as HypoPP-2 with SCN4A variants, and 6 HypoPP-1 patients had CACNA1S variants.
CONCLUSIONS: Our results suggest that SCN4A alleles are the main cause in our cohort, with the remainder caused by CACNA1S alleles, which are the predominant cause in Europe and the United States. Additionally, this study identified 3 novel SCN4A and 2 novel CACNA1S variants, broadening the mutation spectrum of genes associated with PPP.

Hypokalemic periodic paralysis (hypoPP) is a rare channelopathy caused by mutations in skeletal muscle ion channels that usually occurs in young individuals and adolescents. The etiology can be attributed to various factors, such as idiopathic or secondary causes. It is characterized by episodes of sudden flaccid muscle weakness. Timely detection may mitigate the risk of severe complications. Secondary causes of hypoPP, such as hyperthyroidism, should be ruled out, as this could lead to thyrotoxic periodic paralysis. We report the case of a 19-year-old boy who presented to the ED with severe weakness in both the upper and lower extremities. The weakness rapidly progressed to his trunk and was accompanied by acute urinary retention. The physical examination was significant for bilateral upper and lower extremity weakness. Subsequent laboratory investigations revealed markedly low serum potassium levels. The patient\'s symptoms resolved after the replacement of potassium, and he was discharged without neurological deficits. Although rarely accompanied by acute urinary retention, hypoPP must be differentiated from other causes of weakness and paralysis so that the proper treatment can be initiated quickly. The rarity of hypoPP, a condition seldom encountered in clinical practice, and the added rarity of its coexistence with acute urinary retention further underscore the uniqueness of this case report.

The rare neuromuscular disease known as hypokalemic periodic paralysis (hypoKPP), which results in severe muscle weakness in the extremities, is brought on by abnormalities in potassium transport within cells. Laboratory testing is confirmatory, which reveals notably low potassium levels, causing paralysis, which improves once the low potassium is restored. The patient generally complains of muscle weakness with difficulty in performing activities of daily living and impaired participation in functional tasks, with few suffering from coexisting sensory impairments. Physiotherapy generally plays a symptomatic role with motion exercises for the affected muscle groups. There is no standardized physiotherapy protocol for disease-specific impairments. A 46-year-old man complained of bilateral upper and lower limb muscular weakness and was admitted to the neurology ward. The patient also complained of having tingling numbness throughout their entire limbs and had experienced similar episodes of symptoms six months prior. During laboratory evaluation, a significantly low potassium level was found, leading to a diagnosis of hypoKPP. Following medical management, neurophysiotherapy was initiated. Physiotherapy strategy shows significant improvement in muscular strength and functional activities. Thus, this case report concludes that physiotherapy plays a vital role in managing hypoKPP by enhancing muscular strength, functional activities, and quality of life.

The aim of this study was to establish whether bumetanide can abort an acute attack of weakness in patients with HypoPP. This was a randomised, double-blind, cross-over, placebo-controlled phase II clinical trial. Focal attack of weakness was induced by isometric exercise of ADM followed by rest (McManis protocol). Participants had two study visits and received either placebo or 2 mg bumetanide at attack onset (defined as 40 % decrement in the abductor digiti minimi CMAP amplitude from peak). CMAP measurements assessed attack severity and duration. Nine participants completed both visits. CMAP percentage of peak amplitudes in the bumetanide (40.6 %) versus placebo (34.9 %) group at 1hr following treatment did not differ significantly (estimated effect difference 5.9 % (95 % CI: (-5.7 %; 17.5 %), p = 0.27, primary outcome). CMAP amplitudes assessed by the area under the curve for early (0-2hr post-treatment) and late (2-4 h post-treatment) efficacy were not statistically different between bumetanide and placebo (early effect estimate 0.043, p = 0.3; late effect estimate 0.085, p = 0.1). Two participants recovered from the attack following bumetanide intake; none recovered following placebo. Bumetanide was well tolerated but not efficacious to rescue a focal attack in an immobilised hand in the majority of patients, although data supports further studies of this agent.

Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism that manifests as painless flaccid paralysis. An East Asian man in his late 20s presented to the emergency department with an acute onset of quadriparesis associated with hypertonia and hyperreflexia. His initial symptoms and signs suggested involvement of the brain and spinal cord; however, MRI of the neuroaxis was normal. His serum potassium concentration was low, and thyroid test results were consistent with hyperthyroidism. The patient was diagnosed with TPP associated with Graves\' disease and was treated with potassium supplementation, propranolol and methimazole. Motor strength improved to his baseline level of power; bulk was normal, and tone was increased. Although flaccid paralysis is a typical presentation of TPP, brisk reflexes and muscle spasticity cannot rule out this condition. This case highlights the importance of considering TPP as a possible diagnosis in patients presenting with acute quadriparesis.

Patients with familial hypokalemic periodic paralysis (HOKPP) experience episodes of reversible immobility and are at an increased risk of limited sunlight exposure, potentially leading to vitamin D deficiency. However, there is a lack of data on vitamin D levels in this population. We investigated serum vitamin D levels and their associated factors in children with HOKPP. This study included 170 genetically-confirmed children with HOKPP, aged 3-18 years, and 170 age-, sex-, and body mass index (BMI)-matched healthy controls from the Korean Channelopathy Study, a prospective controlled investigation. Anthropometric and clinical characteristics were recorded, and serum levels of calcium, ionized calcium, phosphorus, alkaline phosphatase, 25-hydroxyvitamin D, and intact parathyroid hormone (PTH) were analyzed. Vitamin D deficiency (< 20 ng/mL) was observed in 87.0% of the patients compared to 45.5% of the controls (P < 0.05) during the summer-fall season. During the winter-spring season, 91.7% of the patients and 73.4% of the controls were deficient (P < 0.05). A strong positive correlation was found between onset age of the first paralytic attack and vitamin D levels (r = 0.78, P < 0.01). Conversely, the frequency and duration of paralytic attacks were negatively correlated with vitamin D levels (r = -0.82 and r = -0.65, P < 0.01, respectively). Age, BMI, age at onset, frequency and duration of attacks, and PTH levels were independently associated with vitamin D levels (ß = -0.10, -0.12, 0.19, -0.27, -0.21, and -0.13, P < 0.05, respectively).
CONCLUSIONS: Vitamin D deficiency was highly prevalent in children with HOKPP, and vitamin D levels correlated with various disease characteristics. We recommend routine screening for vitamin D levels in these patients to address this prevalent deficiency. Considering the high prevalence of vitamin D deficiency observed, further research on other diseases characterized by reversible immobility is warranted.
BACKGROUND: • A correlation between immobility and low serum vitamin D levels has been established. However, the vitamin D status of patients with familial hypokalemic periodic paralysis (HOKPP) who experience periods of reversible immobility remains unknown.
BACKGROUND: • Vitamin D deficiency was highly prevalent in children with HOKPP, and vitamin D levels correlated with various disease characteristics.

UNASSIGNED: Hypokalemic periodic paralysis (HypoKPP) is a rare neuromuscular genetic disorder causing recurrent episodes of flaccid paralysis. Most cases are associated with CACNA1S mutation, causing defect of calcium channel and subsequent impairment of muscle functions. Due to defined management approaches early diagnosis is crucial for promptly treatment and prevention new attacks.
UNASSIGNED: We report a case of HypoKPP associated with previously unreported mutation in CACNA1S gene (p.R900M). Molecular modeling of CaV1.1 was applied to evaluate its pathogenicity.
UNASSIGNED: As a patient referred between attacks neurological status, laboratory and neurophysiological examination were unremarkable. Molecular modeling predicted that the p.R900M mutation affects the process of calcium channels activation.
UNASSIGNED: Novel CACNA1S mutation, associated with HypoKPP was identified. Monte-Carlo energy minimization of the CaV1.1 model supported the association of this mutation with this disease.