Hypocalcemic Seizures Research Articles

Hypocalcemia-induced seizures in a peritoneal dialysis (PD) patient: A case report.

A thorough evaluation is necessary for seizures caused by hypocalcemia, both during the patient's presentation and following their recovery from the postictal seizure episode. This is because the underlying cause of hypocalcemia must be ruled out in order to ensure the best possible clinical outcome from calcium and vitamin D therapy. Patients with multiple systemic issues, including neurological involvement and seizure development, are not uncommon among nephrologists. Both the central and peripheral neural systems can be impacted by kidney disease. The main symptoms are myopathy, cranial or peripheral neuropathy, cognitive impairment, and seizures. A 22-year-old female with an unusual medical history who had been known to have end-stage kidney disease (ESKD) for a year and regularly had CAPD (continuous ambulatory peritoneal dialysis) suffered from two episodes of tonic-colonic seizures 2 weeks apart. On physical examination, symptoms of tongue biting, decreased vision in the left eye, and mild bilateral pulmonary air entry were notable. Upon examination, there was evidence of severe hypocalcemia, hyponatremia, a high renal profile (urea and creatinine), anemia, and a severe vitamin D deficiency. Her peritoneal dialysis (PD) prescription was reviewed, her seizures ceased, and she was released from the hospital after the hypocalcemia was treated with intravenous calcium and high doses of vitamin D. The issue of hypocalcemic seizures should be carefully evaluated both at the presentation and after the patient recovers from the postictal stage. By following this, seizure episodes can be prevented with good success if patients strictly adhere to the medication for which they are responsible.

Severe septicemia and electrolyte imbalance in a 2-month-old infant caused by<i> Brevundimonas diminuta</i>

Brevundimonas diminuta, an opportunistic Gram-negative bacterium, is increasingly recognized as a potential pathogen in clinical settings, particularly among immunocompromised individuals. We present a case of B. diminuta bacteremia in a 2-month-old male infant presenting with high-grade fever and hypocalcemic seizures. Despite initial treatment, the patient experienced recurrent seizures, leading to hospital readmission. Microbiological analysis revealed B. diminuta, sensitive to beta-lactam antibiotics and carbapenems. Prompt initiation of targeted antibiotic therapy resulted in significant clinical improvement, highlighting the importance of timely diagnosis and tailored treatment. This case underscores the evolving clinical significance of B. diminuta and emphasizes the need for heightened awareness among health-care providers for effective management of such infections, especially in pediatric patients. Further research collaboration is warranted to better understand the epidemiology and optimal treatment strategies for B. diminuta infections.

Frequency of Hypocalcemic Seizures in Children with Afebrile Seizure: From 2 months - 2 years in a Tertiary Care Hospital

Objective: To determine the frequency of hypocalcemic seizures in children with afebrile seizure from age 2 months - 2 years. Methodology: This Descriptive Cross-Sectional study was conducted in Pediatric Department of Ayub Teaching Hospital Abbottabad for a period of six months (15th April, 2017 to 15th October, 2017). Total 130 cases fulfilling the inclusion criteria were enrolled in the study after approval from ethical committee of hospital and informed consent from the parents of children. A detailed history and examination were done and blood samples for serum calcium level were sent to the hospital laboratory along with other routine investigation to rule out the cause. All data was analyzed using SPSS version 21. Results: Out of 130 cases 48(36.9%) children had hypocalcemia while 82(63.1%) were normocalcemic. 79 (60.8%) were males and 51 (39.2%) were females. The mean age of children was 13.03 ± 6.81 months. The average calcium level was 8.23±1.51mg/dl. Conclusion: It has been concluded that afebrile seizures occur frequently in children with hypocalcemia. Thus, we got the local evidence regarding this association and recommend to screen all new afebrile seizure cases for hypocalcemia. Key words: Hypocalcemic fits, children, afebrile seizures, hypocalcemia

A Rare Compound Heterozygous Mutation of TRPM6 Gene in Hereditary Hypomagnesemia with Secondary Hypocalcemia: A Cause of Refractory Seizures in an Infant

Background: Hypomagnesemia is an important cause of refractory hypocalcemic seizures. Among the causes of hypomagnesemia, genetic defects are rare. Clinical Description: A 20-month-old boy presented with a history of repeated hypocalcemic convulsions since 1 month of age. Besides seizures, the infant was thriving well and otherwise asymptomatic. Management and Outcome: On investigation, he had low serum calcium, normal vitamin D, low parathormone, and very low serum magnesium (0.5 mg/dl) levels, with normal sodium, potassium levels, and renal functions. The child was initiated on parenteral magnesium supplementation and subsequently discharged on high-dose oral magnesium supplementation. As further investigations ruled out common causes of hypomagnesemia, clinical exome sequencing was done, which revealed a compound heterozygous state with two variants in the TRPM6 gene NM_017662.5, one being a missense variant (chr9: c.5614T>C, [p.Trp1872Arg]/Heterozygous) and the other being a frameshift deletion (chr9: c.1939_1946delGCAATGGC, [p.Ala647Profs*2]/Heterozygous). The child maintained normal serum magnesium levels at follow-up and was seizure-free. Conclusion: Hereditary hypomagnesemia with secondary hypocalcemia is a rare cause of refractory seizures with onset since early infancy. Here, a compound heterozygous variant of the TRPM6 gene was identified as the cause of this condition.

Case report - congenital ichthyosis and hypoparathyroidism with hypocalcemic seizures in a teenager

Case report - congenital ichthyosis and hypoparathyroidism with hypocalcemic seizures in a teenager

Frequency of hypomagnemsemia in neonate with hypocalcemic seizures presenting to a Tertiary Care Hospital.

Frequency of hypomagnemsemia in neonate with hypocalcemic seizures presenting to a Tertiary Care Hospital.

433 - Acute respiratory failure and hypocalcemic seizures secondary to severe nutritional rickets

433 - Acute respiratory failure and hypocalcemic seizures secondary to severe nutritional rickets

Congenital continuous retrograde basilar flow suggests type B interrupted aortic arch in a neonate: A case report

Reversed flow in the basilar artery can be acquired or congenital. Acquired reversed flow in the basilar artery can result from acute thrombosis of the basilar artery or retrograde vertebral artery flow. Congenital continuous retrograde basilar artery flow has not been described. We report a 2-day-old male presenting with hypocalcemic seizures which led us to obtain a Duplex echoencephalogram. An echocardiogram was subsequently ordered. In the coronal plane through the anterior fontanelle, retrograde flow was seen in the basilar artery and the right vertebral artery. In the axial plane through the temporal window, the flow was anteroposterior in both posterior communicating arteries. In the posterior cerebral arteries, the flow was retrograde in the P1 segment and anterograde in the P2 and P3 segments. An interrupted aortic arch was suspected. The echocardiogram showed a large perimembranous ventricular septal defect with bidirectional shunting, a hypoplastic and bicuspid aortic valve, an aortic arch interrupted between the left common carotid artery and the left subclavian artery (type B interrupted aortic arch), and a 5 mm patent ductus arteriosus with predominant right to left flow. Because of the patency of the large patent ductus arteriosus, our patient showed no sign of posterior circulation insufficiency. Prostaglandin E1 therapy was initiated immediately. Diagnosis of DiGeorge syndrome was proven. The infant underwent interrupted aortic arch repair and anterograde flow was established in the basilar artery. We conclude that congenital asymptomatic continuous retrograde flow in the basilar artery and left vertebral artery is a medical emergency as it implies the presence of type B interrupted aortic arch with large patent ductus arteriosus in a neonate.

Infantile hypocalcemic seizures secondary to maternal vitamin D deficiency followed by persistent hypomagnesemia

Infantile hypocalcemic seizures secondary to maternal vitamin D deficiency followed by persistent hypomagnesemia

OR23-02 Genotype-Phenotype Correlation In Calcium Sensing Receptor (Casr) Gene Gain-Of-Function Mutations: A Case Series And Report Of 2 Novel Mutations

Abstract Disclosure: D.S. Ali: None. F. Marini: None. F. Alsarraf: None. H.H. Alalwani: None. A. Alamri: None. A.A. Khan: Advisory Board Member; Self; Amgen Inc, Takeda. Grant Recipient; Self; Amgen Inc, Alexion Pharmaceuticals, Inc., Takeda, Ultragenyx, Radius Health, Inc. M. Brandi: Consulting Fee; Self; Alexion Pharmaceuticals, Inc. Speaker; Self; Amgen Inc, Alexion Pharmaceuticals, Inc., Eli Lilly & Company. Background: Autosomal dominant hypocalcemia (ADH1) is a genetic disorder characterized by low serum calcium and low or inappropriately normal parathyroid hormone levels. It is caused by a heterozygous activating mutation of the calcium-sensing receptor (CaSR) gene. ADH1 has been linked to 113 unique germline mutations, of which 96% are missense mutations. There is a lack of clear genotype-phenotype correlation in the reported literature. Methods: We described a case series of six unrelated ADH1 probands, each with a gain-of-function CaSR mutation, and two children of one of these cases, comparing clinical, biochemical, and complication profiles and matching our identified mutations to those previously reported in the literature. Results: Of our cases 75% are familial and 25% are secondary to de novo mutation. Our 6 unrelated ADH1 probands showed distinct clinical presentations, while 3 cases within the same pedigree shared similar presentation and clinical characteristics including presentation in infancy, hypocalcemic seizures (2/3; 66.7%), hypomagnesemia, hyperphosphatemia, and hypercalciuria. The biochemical profile differed among the 6 cases in the degree of hypocalcemia, associated hypercalciuria, hypomagnesemia, and/or hypokalemia. Response to therapy also differed. When comparing our cases to previously published cases, we noted that mutations in the 5th transmembrane domain of the CaSR (TM5) carry a more severe form of the disease and may be associated with a higher rate of hypocalcemic seizures, basal ganglia calcifications as well as nephrocalcinosis, nephrolithiasis and renal insufficiency compared to mutations in the extracellular regions. Hypomagnesemia was present in 100% of the cases harboring mutations in TM5. We also describe two novel activating mutations of the CaSR gene; c.2468T>A, p.lle823Asn and c.1756G>A, p.Glu586Lys. Both of these were not reported either on the most common databases of human mutations or in the literature. In silico analysis of p.lle823Asn by PolyPhen-2 predicted the Ile to Asn substitution at position 823 as “probably damaging”, while the p.Glu586Lys substitution was suggested to have a “benign” nature. Our patient with the former mutation had a history of seizure and nephrolithiasis, while our patient with the latter mutation is mildly symptomatic, presented in her 40s, and is on low doses of active vitamin D and calcium supplements. Conclusion: As a result of these genetic and clinical comparisons, we propose that a genotype-phenotype correlation may exist because our cases showed similar presentation, characteristics, and severity, with respect to published cases with the same or similar mutations. We also contended that the severity of the presentation is highly influenced by the specific CaSR variant. These findings, however, require further evaluation and assessment with a systematic review. Presentation: Saturday, June 17, 2023

SAT229 Symptomatic Hypocalcemia In The Setting Of Crohn’s Disease With Severe Hypomagnesemia

Abstract Disclosure: K. Cuan: None. T. Reisman: None. Introduction: People with Crohn’s Disease (CD) are at risk for various nutritional deficiencies due to decreased oral intake, malabsorption, and increased intestinal losses. CD often causes a negative calcium balance, which does not usually cause hypocalcemia because the bones serve as a reservoir for calcium. However, symptomatic hypocalcemia may occur if a concurrent severe hypomagnesemic state is present. The factors resulting in hypocalcemia in patients with magnesium deficiency are impaired PTH secretion, PTH resistance, and vitamin D deficiency. Clinical Case: A 33-year-old man with CD and rheumatoid arthritis presented following a seizure with additional symptoms of hand cramping and facial twitching. He had previously undergone three small bowel resections and had a history of hypocalcemia due to malabsorption. Although this patient had previously been admitted due to a hypocalcemic seizure, he did not start oral calcium supplements at that time. No issues with magnesium were identified previously. On this encounter, he was found to have a corrected calcium (cCa) of 5.3 mg/dL, undetectably low magnesium at <0.7 mg/dL, normal phosphorus, 25-hydroxyvitamin D at 3.5 ng/mL, and an elevated intact PTH (iPTH) at 169 pg/mL. Aggressive intravenous calcium and magnesium repletion improved cCa to 7.4 mg/dL and magnesium to 2 mg/dL with no further seizure activity. He was discharged on calcium carbonate, calcitriol, and ergocalciferol. A month later, he presented to our endocrinology clinic asymptomatic but with a cCa of 6 mg/dL and magnesium at <0.7 mg/dL. Further biochemical workup revealed normal phosphorus, 25-hydroxyvitamin D at 7.9 ng/mL, and an inappropriately normal iPTH at 49 pg/mL. He was readmitted to the hospital where intravenous repletion improved cCa to 8.1 mg/dL and magnesium to 1.9 mg/dL. His recurrent hypomagnesemia was attributed to malabsorption. An increased dose of calcitriol and oral magnesium were added to his discharge medication regimen, in addition to his ergocalciferol and calcium carbonate. Three days later, he had a cCa level of 7.1 mg/dL as an outpatient. Conclusion: Patients with CD often have nutrient deficiencies, especially if they have had surgical resection within the intestinal tract. Our patient initially developed hypocalcemia from malabsorption, which was then exacerbated by the severely hypomagnesemic state. During his initial hospital encounter, the elevated iPTH level indicated PTH resistance. On his second encounter, the normal iPTH level suggested hypoparathyroidism. Given the relationship between magnesium and calcium homeostasis, addressing the hypomagnesemia eventually aided in achieving stabilization of serum calcium levels. Thus, in patients who are at risk for malabsorption and have recurrent symptomatic hypocalcemia, it is prudent to check magnesium levels as it can affect long term management of hypocalcemia. Presentation: Saturday, June 17, 2023

Late-onset hypocalcemia seizure: An interesting presentation of sporadic maternal primary hyperparathyroidism with hypovitaminosis D

Abstract The cardinal manifestation of primary hyperparathyroidism is secondary to hypercalcemia and high bone turnover disease due to sustained elevation of parathyroid hormone. A high index of suspicion for maternal primary hyperparathyroidism should be kept in the setting of neonatal hypocalcemia. Delayed presentation of hypocalcemic seizure secondary to maternal primary hyperparathyroidism is infrequent. Herein, we report a case of a 2-month-old infant who presented with late-onset (>72 h) hypocalcemic seizure, biochemically mimicking pseudohypoparathyroidism, which eventually led to the diagnosis of maternal hyperparathyroidism with vitamin D deficiency.

Malignant Infantile Osteopetrosis: A Rare Cause of Refractory Hypocalcemia

Background: Infantile malignant osteopetrosis (IMO) is a rare autosomal recessive disease characterized by a higher bone density in bone marrow caused by the dysfunction of bone resorption. Clinical Description: A 2-month-old baby boy presented with features of lower respiratory tract infection, along with a swollen right upper arm due to fracture of humerus, along with signs of bicytopenia and hepatosplenomegaly. He had a history of hypocalcemic seizures at 8th day of life. Management and Outcome: Current hospitalization revealed refractory hypocalcemia and hypophosphatemia with normal to increased Vitamin D and parathormone levels and increased density of bone. Hypocalcemia was particularly refractory in nature needing multiple intravenous calcium corrections. Whole exome sequencing detected compound heterozygous variants in the T-cell immune regulator 1 pathogenic gene of IMO. Simultaneously, a heterozygous nonsense variation in exon 4 of the CHRNA4 gene was detected causing nocturnal frontal lobe epilepsy. As the infant had evidence of bone marrow failure, he was considered and referred for hematopoietic stem cell transplantation. Conclusion: Neonatal and early infantile hypocalcemia are commonly seen by pediatricians, but an etiology of IMO is rarely considered. The presence of fracture of long bones with cytopenias and hepatosplenomegaly in a young infant with recurrent hypocalcemia, without Vitamin D deficiency, should raise suspicion of this disorder and genetic analysis should be carried out for the same.

Analysis of a series of Italian APECED patients with autoimmune hepatitis and gastro-enteropathies.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome is a rare monogenic disease determined by biallelic mutations in AIRE gene, which encodes a transcription factor essential for central immune tolerance. Classic diagnosis is determined by the presence of two of the main APECED clinical diseases: chronic mucocutaneous candidiasis, chronic hypoparathyroidism, and Addison's disease. Non-endocrine autoimmunity, involving the liver, intestine, eyes, and kidneys, is generally reported in a minority of European patients, while American APECED patients have a higher tendency of developing organ-specific non-endocrine manifestations early in life. This observation led to the revision of the diagnostic criteria to permit earlier diagnosis based on the appearance of one classic triad symptom or one non-classical manifestation at a young age in the presence of IFNωAbs or AIRE mutations (Ferre-Lionakis criteria). We analyzed the clinical, genetic, and autoantibody (Ab) profiles in a series of 14 pediatric Italian APECED patients with gastrointestinal manifestations (seven male and seven female patients). Ten patients presented hepatitis (APECED-associated hepatitis (APAH)), while seven were affected by constipation, diarrhea, and malabsorption. Four patients had developed APAH before classic triad symptoms. Based on the age of appearance of non-endocrine manifestations including APAH and gastro-enteropathy, the Ferre-Lionakis criteria would have allowed an expedited diagnosis in 11/14 patients. Abs to tryptophan hydroxylase (TPHAb) and hepatic aromatic l-amino acid decarboxylase (AADC) were significantly associated with APECED patients of the present series. Abs to cP4501A2 were detectable in the serum of 4/8 patients with APAH, and Abs to cP4502A6 were detectable in 3/8 patients. AADC Abs tested positive in 5/7 patients, which is indicative of gastrointestinal dysfunction in APECED and TPHAb in 5/7 patients with gastrointestinal dysfunction. IFNAb was significantly associated with the syndrome. Although Ferre-Lionakis expanded criteria applied to the American cohorts of APECED patients would require validation in independent large cohorts of European patients, the results of this study emphasize the importance to evaluate the presence and the age of appearance of APAH and autoimmune enteropathy even in European cohorts for an earlier APECED diagnosis. An earlier APECED diagnosis would also allow the prevention of episodes of life-threatening hypocalcemic seizures and adrenal crisis, which are the main manifestations of undiagnosed APECED.

Cord vitamin D levels in newborns and its clinical correlation

Vitamin D levels in newborns mainly depend on maternal vitamin D levels and maternal-fetal transfer of Vitamin D and its metabolites during pregnancy. Babies born to mothers with marked Vitamin D deficiency may have neonatal Rickets. There are many factors determining the Vitamin D levels in mother, like skin pigmentation, duration of sunlight exposure, body mass index, degree of altitude, clothing, sunscreen use, weather, air pollution, season and time of the day. Mothers with light - colored skin require a lesser duration of exposure as compared to mothers with dark-colored skin. If left untreated, children can develop hypocalcemic seizures, growth failure, irritability, lethargy, respiratory infections, and allergies, tetany, and laryngospasm and even dilated cardiomyopathy. Hence we performed this study to evaluated the role of cord vitamin D levels. Methods this was a prospective observational study performed on term neonates weighing > 2.5 kg. Cord vitamin D was estimated at birth, and correlated with various maternal parameters such as anaemia, sun exposure, co-morbidities etc. Results: the mean cord vitamin D levels were low in those babies born to mothers with anaemia, lack of pre-natal supplementation of vitamin D and calcium, as well as less sun exposure. Conclusion: Cord vitamin D could be a marker of vitamin D deficiency in neonates born to mothers with risk factors like anaemia, lack of sun exposure and supplementation.

Clinical & etiological profile of new onset unprovoked seizure in children aged 2 months to 18 years

Seizure is defined as abnormal paroxysmal neuronal discharge, which is clinically manifested by motor, sensory, autonomic or behavioral disturbances. Seizures are common in pediatrics age group and occur in 10% of children. Less than 1/3of seizures in children are caused by epilepsy. The objective of the study was to determine the clinical and etiological profile of new onset unprovoked seizure in children aged between 2 month to 18 years. A hospital based prospective single centre study at RNT Medical College, Udaipur. 111 patients admitted in Balchikitsalya with new onset unprovoked seizures during one year. Out of 111 patients with new onset unprovoked seizures, majority of patients were between 1-5 years of age with male predominance. In which most common diagnosis was seizure disorder in 78 pts (70.2%) [Generalised 76 pts (97.4%) > Focal 2 pts (2.6%)] followed by 13.5% hypocalcemic seizure, 8.1% hypoglycemic seizure. Other diagnosis was tuberous sclerosis (2.7%), white matter changes (1.8%), adrenoleukodystrophy (0.9%), arachnoid cyst (0.9%), tuberculoma (0.9%) and HIE changes (0.9%). EEG abnormality was seen in 46% of patients. Hyponatremia (36%) was significantly associated with abnormal EEG changes. MRI was done in 38.7% of the patients, out of which, abnormality was seen in only 8.6% of the children. Seizure is mainly diagnosed clinically and EEG can be normal in many patients. First episode of unprovoked seizure was common in age group of 1-5 years. EEG and Neuroimaging is useful for better diagnosis, treatment can be started on clinical diagnosis.

Maternal hypovitaminosis D presenting as late-onset hypocalcemic seizure in a term neonate: a case report

BackgroundVitamin D deficiency is a known morbidity among pregnant women. Maternal hypovitaminosis D results in poor fetal transplacental vitamin D accretion and decreased stores in the neonate. This in turn may lead to hypocalcemia in neonates, having presentations from being asymptomatic and tremors to hypocalcemic seizures. There are fewer case reports of hypocalcemic neonatal seizures as a result of maternal vitamin D deficiency.Case presentationA term male neonate developed multiple episodes of multifocal seizures on day six of life associated with hypocalcemia. He was also found to have hyperphosphatemia, raised alkaline phosphatase, and elevated parathormone levels with normal serum magnesium and renal function tests. Neonate and maternal serum vitamin D3 levels were also low. A diagnosis of late-onset hypocalcemic seizure secondary to maternal hypovitaminosis D was made and the baby made an uneventful recovery with parenteral calcium and oral vitamin D supplementation. On follow-up with therapy, the baby remained asymptomatic with normal serum calcium, phosphate, and vitamin D3 levels.ConclusionHypovitaminosis D must also be considered as a contributing factor for late-onset hypocalcemic seizure in neonates.

Hypocalcemic Seizures in Infancy and its Relationship with Maternal Vitamin D Deficiency

Background: Hypocalcemia accounts for a large number of seizures in infants presented at the emergency department of our hospital.
 Objective: To evaluate the role of Vitamin D deficiency as the etiology of hypocalcemic seizures in infancy and its relationship with maternal Vitamin D levels.
 Methods: Cross sectional hospital based study over a period of 35 months from July 2016 to June 2019. Total 60 infants with hypocalcemic seizures were enrolled into the study. Blood samples were taken for serum total calcium, inorganic phosphate, alkaline phosphatase, albumin, 25(OH)D and PTH from the child. Maternal serum 25(OH)D levels were measured as well.
 Results: The mean age of the studied infants was 3.6 (±1.2) months. All patients had low total calcium (mean 6.5 mg/dl) and most of them had low inorganic phosphate (mean 3.5 mg/dl), while all of them had raised alkaline phosphatase (mean 1093.50 IU/L) and PTH levels (mean104 pg/ml) at presentation. Forty percent of infants were severely deficient and 60% were deficient in vitamin D; none of them were vitamin D sufficient. Among their mothers, none were sufficient, 10% were insufficient, 45% were deficient, and 45% were severe deficient of vitamin D. Neonatal 25(OH)D showed strong negative correlation with their serum PTH levels and strong positive correlations with maternal serum 25(OH)D levels.
 Conclusion: All infants in our setting presented with hypocalcemic seizures were found due to Vitamin D deficiency and it was mostly related to maternal Vitamin D deficiency.
 DS (Child) H J 2021; 37(2): 98-102

Syndromic and non-syndromic etiologies causing neonatal hypocalcemic seizures.

The diagnosis of neonatal hypocalcemic seizures (HS) in newborns is made based on clinical signs and serum calcium level. Their etiology is broad and diverse, and timely detection and initiation of treatment is essential. We retrospectively reviewed 1029 patients admitted to the neonatal intensive care unit. Neonatal HS were diagnosed in 16 patients, and we compared etiologies and clinical outcomes, including clinical seizures and neurodevelopment at least over 1 year old. The etiologies can be broadly categorized into 5 syndromic and 11 non-syndromic neonatal HS. Syndromic neonatal HS included 3 Digeorge syndrome, 1 Kleefstra syndrome and 1 Alström syndrome. Non-syndromic neonatal HS included 8 vitamin D deficiency, 1 hypoparathyroidism, and 2 hypoxic-ischemic encephalopathy. Patients with syndromic neonatal HS were found to have worse clinical outcomes than those with nonsyndromic HS. In eight patients with vitamin D deficiency, neurodevelopment was normal. Five of five patients (100%) with syndromic HS used two or more antiseizure drugs. However, among patients with non-syndromic neonatal HS, only one of 11 (9.1%) used more than one drug (p = 0.001). This finding highlighted that syndromic hypocalcemic seizures in newborns have worse neurodevelopmental outcomes and are more often difficult to manage, and would benefit from a genetic diagnostic approach.

PSAT204 Hypoparathyroidism due to a Novel Mutation as the Initial Presentation of Non-classical Autoimmune Polyglandular Syndrome Type 1

Abstract Background Autoimmune polyglandular syndrome type 1 (APS-1) is a rare disorder, with an estimated worldwide prevalence of 1 in 80-100,000, resulting from a mutation in the autoimmune regulator (AIRE) gene responsible for immune tolerance. It is characterized by the presence of 2 or 3 cardinal disorders – primary adrenal insufficiency, chronic mucocutaneous candidiasis, and hypoparathyroidism. It is now known that APS-1 presents in 2 forms – the classic autosomal recessive form, which presents early in life with at least 2 of 3 components of the clinical triad, and the non-classical form, which is caused by a dominant heterozygous mutation and usually presents later in life with a milder clinical phenotype and incomplete penetrance.Clinical case:A 29-year-old African American female presented to the clinic with symptoms of twitching, cramping, and paresthesias. She was diagnosed with hypoparathyroidism at age 18 years, which was complicated by hypocalcemic seizures. She was taking calcium and calcitriol with fluctuating calcium levels. Other medical problems included hypertension and anxiety. She denied having frequent infections or history of autoimmune disorders. She reported regular menses. Her family history was negative for autoimmune disease and calcium disorders. Physical examination revealed a well-developed woman with unremarkable vitals and BMI 35.9 kg/m2. She had positive Chvostek's sign bilaterally, negative trousseaus sign, 2+ reflexes throughout and normal gait. She had no onychomycosis, mucocutaneous candidiasis, hyperpigmentation, or vitiligo. She had a normal cardiac, respiratory, and abdominal examination. Lab work up was remarkable for calcium 6.4 mg/dL (8.1-10.4), PTH 6 pg/mL (11.1-79.5), eGFR 104 ml/min/m2 (normal: >90), 24-hour urinary calcium (<1 mg/24hours) & creatinine 1.0 g/24hours, vitamin D25-OH 26.23 ng/ml (25-80), magnesium 1.7 mg/dL (1.3-2.7), vitamin B12 level 445 pg/mL (211-911) and TSH 2.243 mcIU/mL (0.4-4.7). She had negative antibodies to TPO, TTG IgA, 21-hydroxylase, IA-2, and GAD65. Plain films did not identify intracranial calcifications or nephrolithiasis. Genetic evaluation revealed a heterozygous mutation in the AIRE gene c.718 G>A in exon 6, p.G240S consistent with non-classic APS-1. Conclusion This case highlights the importance of genetic testing in patients with isolated hypoparathyroidism. Our case had a novel mutation (c.718 G>A) in the SAND domain of the AIRE gene, in contrast to the majority of prior non-classical APS-1 mutations which are localized to the 1st plant homeodomain (PHD-1) of AIRE gene. It is important to report the clinical features of these patients with novel mutations as it can enrich our understanding and contribute to future research. It is important to establish a diagnosis of APS-1, as these patients are at risk for both endocrine and other autoimmune manifestations which may manifest during its natural history. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.