Extrapyramidal Symptoms and Advanced Calcification of the Basal Ganglia in a Patient with Autosomal Dominant Hypocalcemia

Kurozumi, Akira; Okada, Yosuke; Arao, Tadashi; Endou, Itsuro; Matsumoto, Toshio; Tanaka, Yoshiya

doi:10.2169/internalmedicine.52.8375

Cited by 12 publications

(10 citation statements)

References 17 publications

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“…ADH patients have mild to moderate hypocalcemia with low to normal PTH levels and an inappropriately normal or high urinary calcium excretion (21). Patients suffer from symptoms of hypocalcemia, develop tissue calcifications especially in the brain and kidney (22,23,24) and sometimes show defects in bone mineralization (25). A single mutated CASR allele suffices to produce ADH and there is only one case in the literature with a homozygous activating CASR mutation (26).…”

Section: Mutations Causing Gain Of Casr Functionmentioning

confidence: 99%

GENETICS IN ENDOCRINOLOGY: Gain and loss of function mutations of the calcium-sensing receptor and associated proteins: current treatment concepts

Mayr¹,

Schnabel²,

Dörr³

et al. 2016

European Journal of Endocrinology

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The calcium-sensing receptor (CASR) is the main calcium sensor in the maintenance of calcium metabolism. Mutations of the CASR, the G protein alpha 11 (GNA11) and the adaptor-related protein complex 2 sigma 1 subunit (AP2S1) genes can shift the set point for calcium sensing causing hyper-or hypo-calcemic disorders. Therapeutic concepts for these rare diseases range from general therapies of hyper-and hypo-calcemic conditions to more pathophysiology oriented approaches such as parathyroid hormone (PTH) substitution and allosteric CASR modulators. Cinacalcet is a calcimimetic that enhances receptor function and has gained approval for the treatment of hyperparathyroidism. Calcilytics in turn attenuate CASR activity and are currently under investigation for the treatment of various diseases. We conducted a literature search for reports about treatment of patients harboring inactivating or activating CASR, GNA11 or AP2S1 mutants and about in vitro effects of allosteric CASR modulators on mutated CASR. The therapeutic concepts for patients with familial hypocalciuric hypercalcemia (FHH), neonatal hyperparathyroidism (NHPT), neonatal severe hyperparathyroidism (NSHPT) and autosomal dominant hypocalcemia (ADH) are reviewed. FHH is usually benign, but symptomatic patients benefit from cinacalcet. In NSHPT patients pamidronate effectively lowers serum calcium, but most patients require parathyroidectomy. In some patients cinacalcet can obviate the need for surgery, particularly in heterozygous NHPT. Symptomatic ADH patients respond to vitamin D and calcium supplementation but this may increase calciuria and renal complications. PTH treatment can reduce relative hypercalciuria. None of the currently available therapies for ADH, however, prevent tissue calcifications and complications, which may become possible with calcilytics that correct the underlying pathophysiologic defect.

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Section: Mutations Causing Gain Of Casr Functionmentioning

confidence: 99%

GENETICS IN ENDOCRINOLOGY: Gain and loss of function mutations of the calcium-sensing receptor and associated proteins: current treatment concepts

Mayr¹,

Schnabel²,

Dörr³

et al. 2016

European Journal of Endocrinology

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“…Esant mažai PTH koncentracijai, kalcis pašalinamas per inkstus, jo mažiau reabsorbuojama žarnyne. Hipoparatirozei būdinga maža PTH koncentracija, hipokalcemija ir hiperfosfatemija [3]. Dažniausia įgytos hipoparatirozės priežastis -prieskydinių liaukų destrukcija: pašalinimas arba pažeidimas skydliaukės ir kitų kaklo srities operacijų metu, radiacinis arba infiltracinis prieskydinių liaukų suardymas, hipoparatirozė gali būti idiopatinė arba genetinio sindromo dalis (DiGeorge sindromas) [4].…”

Section: Hipokalcemijos Priežastysunclassified

“…Nervų sistemos pažeidimui būdinga tetanija, toniniai traukuliai, epileptiforminis aktyvumas [3,9]. Hipokalcemijai būdingi Chvosteko ir Trousseau simptomai, tačiau Chvosteko simptomas randamas net 10 proc.…”

Section: Hipokalcemijos Klinikaunclassified

“…sveikų žmonių [1]. Kai hipokalcemija tęsiasi ilgai, galvos smegenų KT matoma pamato branduolių kalcifikacija, tačiau ekstrapiramidiniai simptomai pasireiškia itin retai [3]. Pamato branduolių kalcifikacija nustatoma net iki 69 proc.…”

Section: Hipokalcemijos Klinikaunclassified

“…Pamato branduolių kalcifikacija nustatoma net iki 69 proc. sergančiųjų idiopatiniu hipoparatiroidizmu [3], ji siejama su hiperfosfatemija [10]. Simetriški kalcinatai randami pacientams, sergantiems Fahro liga, tačiau tuomet nenustatoma kalcio ir fosforo apykaitos sutrikimo [10].…”

Section: Hipokalcemijos Klinikaunclassified

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Hipokalcemija ‒ Žinoma, Bet Neatpažįstama Būklė. Atvejo Pristatymas Ir Trumpa Literatūros Apžvalga

Narkutė

Damulevičienė

2017

Medicinos Teorija Ir Praktika

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SANTRAUKAReikšminiai žodžiai: hipokalcemija, pirminis hipoparatiroidizmas, ilgas QT intervalas, parkinsonizmas. Hipokalcemija kliniškai pasireiškia nervų ir raumenų sistemų simptomais: tetanija, traukuliais, laringospazmu, aritmijomis, sunkina širdies nepakankamumą. Viena hipokalcemijos priežasčių yra pirminis hipoparatiroidizmas -retas endokrininis sutrikimas, kuriam būdinga hipokalcemija, hiperfosfatemija ir maža parathormono (PTH) koncentracija kraujyje. Hipokalcemiją taip pat gali sukelti pseudohipoparatiroidizmas, kai PTH koncentracija normali ar padidėjusi, vitamino D trūkumas, ūminis ir lėtinis inkstų nepakankamumas, pankreatitas, įvairūs medikamentai. Pristatomas paciento, kuriam diagnozuota simptominė hipokalcemija dėl pirminio hipoparatiroidizmo, klinikinis atvejis. Kliniškai stebėtas traukulių priepuolis, galvos smegenų EEG registruotas epileptiforminis aktyvumas, EKG -ilgas QT intervalas, o galvos smegenų KT buvo nustatyti kalcinatai pamato branduolių ir smegenėlių srityse, galimai sukėlę parkinsonizmo simptomus. Skyrus gydymą kalcio gliukonatu į veną, o vėliau koreguojant hipokalcemiją kalcio karbonatu ir alfakalcidoliu, paciento būklė ženkliai pagerėjo, traukuliai nesikartojo, tačiau išlaikyti normalią kalcio koncentraciją kraujyje buvo sudėtinga, EKG išliko ilgas QT intervalas. Pacientas konsultuotas endokrinologo, diagnozuotas pirminis hipoparatiroidizmas. Tolesniam gydymui rekomenduota tęsti kalcio preparatų ir alfakalcidolio vartojimą, ambulatoriškai monitoruoti kalcio ir fosforo koncentraciją kraujyje. ABSTRACTKey words: hypocalcaemia, primary hypoparathyroidism, long QT interval, parkinsonism. Hypocalcaemia affects nervous and muscular systems, the main clinical symptoms include tetany, seizures, laryngospasm and arrythmias, the condition worsens heart failure. Primary hypoparathyroidism is a rare endocrine disorder that causes hypocalcaemia, significantly elevated plasma phosphorus and low parathormone concentration. Hypocalcaemia can also be caused by pseudohypoparathyroidism, when serum concentration of parathormone is normal or elevated, vitamin D deficiency, acute or chronic renal failure, acute pancreatitis, various medication. We present a clinical case of clinically relevant hypocalcaemia due to primary hypoparathyroidism. Clinical presentation included seizures, epileptiformic activity on EEG, long QT interval on ECG, and calcification of basal ganglia and cerebellum that potentially has caused parkinsonism. We started treatment with calcium gluconate intravenously wich was folowed by calcium and alphacalcidol. Patient's condition improved, seizures did not repeat, however it was difficult to maintain normal blood calcium concentration, long QT interval persisted on ECG. The patient was consulted by endocrinologist and diagnosed with primary hypoparathyroidism. For the following treatment it was recommended to continue taking calcium and alphacalcidol, and to monitor blood calcium and phosphorus concentrations.

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Co‐occurrence of a novel PDGFRB variant and likely pathogenic variant in CASR in an individual with extensive intracranial calcifications and hypocalcaemia

DeMeo

Burgess

Blackburn

et al. 2017

Clinical Case Reports

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Key Clinical MessageThis case report describes an individual with brain calcifications, cognitive decline, motor dysfunction, and hypocalcaemia. Exome sequencing revealed a previously reported variant in the CASR gene and a variant of uncertain significance in PDGFRB. The clinical phenotype is likely explained by the CASR variant, but we discuss how the PDGFRB variant could also participate in the phenotype.

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Extrapyramidal Symptoms and Advanced Calcification of the Basal Ganglia in a Patient with Autosomal Dominant Hypocalcemia

Cited by 12 publications

References 17 publications

GENETICS IN ENDOCRINOLOGY: Gain and loss of function mutations of the calcium-sensing receptor and associated proteins: current treatment concepts

GENETICS IN ENDOCRINOLOGY: Gain and loss of function mutations of the calcium-sensing receptor and associated proteins: current treatment concepts

Hipokalcemija ‒ Žinoma, Bet Neatpažįstama Būklė. Atvejo Pristatymas Ir Trumpa Literatūros Apžvalga

Co‐occurrence of a novel PDGFRB variant and likely pathogenic variant in CASR in an individual with extensive intracranial calcifications and hypocalcaemia

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