Etiologic diagnosis of seizure requires proper consideration of apparently unrelated clinical features of the patient. Here, we report the case of a patient of status epilepticus with moderate-to-severe bilateral sensorineural deafness. Investigations showed extensive intracranial calcification, hypoparathyroidism and unilateral renal agenesis. The features were consistent with Barakat syndrome, a rare developmental disorder associated with mutations in the GATA3 gene. To the best of our knowledge, this is the first reported case of Barakat syndrome from India

Bashardoust, Bahman

Iranparvar Alamdari, Manouchehr

Maleki, Nasrollah

Tavosi, Zahra

Case Reports in Nephrology

PubMed

Bushehr University of Medical Sciences Repository

Hindawi Publishing CorporationCase Reports in NephrologyVolume 2013, Article ID 261907, 4 pageshttp://dx.doi.org/10.1155/2013/261907Case ReportSeizure, Deafness, and Renal Failure: A Case ofBarakat SyndromeNasrollah Maleki,1 Bahman Bashardoust,1Manouchehr Iranparvar Alamdari,1 and Zahra Tavosi21 Department of Internal Medicine, Imam Khomeini Hospital, Ardabil University of Medical Sciences, Ardabil, Iran2Department of Internal Medicine, Shohadaye Khalije Fars Hospital, Bushehr University of Medical Sciences, Bushehr, IranCorrespondence should be addressed to Nasrollah Maleki; malekinasrollah@yahoo.comReceived 12 August 2013; Accepted 8 September 2013Academic Editors: Y. Fujigaki and H. SchifflCopyright © 2013 Nasrollah Maleki et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.Barakat syndrome (also known as HDR syndrome) is an autosomal dominant disorder characterized by hypoparathyroidism,sensorineural deafness, and renal disease caused bymutation of theGATA3 gene located at chromosome 10p15.The exact prevalenceof this disorder is not known but is very rare, with only about a dozen cases reported in the literature. Here, we report a case of 58-year-oldman fromArdabil who presentedwith seizure due to hypocalcemia. Further history revealed bilateral deafness. Audiogramconfirmed sensorineural hearing loss of both sides. His laboratory data were consistent with hypoparathyroidism and renal failure.He was diagnosed to have Barakat syndrome based on his clinical and laboratory data. In conclusion, we need to be aware of rareinherited conditions in a patient with abnormal physical and laboratory findings even though their initial presentation was seizureand hypocalcemia.1. IntroductionBarakat syndrome, also known as hypoparathyroidism, deaf-ness, and renal dysplasia (HDR) syndrome, is a rare autoso-mal dominant disorder [1]. The syndrome was first noted insiblings with hypocalcemia and proteinuria [2]. Mutations inGATA3, a gene localized to the chromosome region 10p14-15, have been detected in families affected by the syndrome[3, 4]. GATA3 is a transcription factor that is involved in theembryonic development of the parathyroid glands, kidneys,inner ears, thymus, and central nervous findings. Similarclinical findings were reported in families with an apparentautosomal recessive mode of inheritance [5, 6].In this report, we demonstrate a case of Barakat syndromepresented with seizure, hypoparathyroidism, and bilateralsensorineural deafness.2. Case ReportA 58-year-old man from Ardabil was admitted to our hos-pital with generalized tonic-clonic seizure. The patient wasa known case of chronic kidney disease 2 years ago. Hehad been experiencing recurrent episodes of seizure for20 days before his admission. Further history revealedprogressive hearing loss for the last 10 years but therewas no developmental delay. He had a family history ofkidney disease in siblings, which in their renal biopsy werereported to have FSGS. His vital signs were within thenormal range. Neurological examination showed depressionof deep tendon reflexes in both upper and lower extremities.Chvostek’s and Trousseau’s signs were negative. The initiallaboratory studies showed serum calcium level: 5.3mg/dLand serum phosphorus level: 7.2mg/dL. The serum intact-PTH level measured by immunoradiometric assay (IRMA)was 5 ng/L (normal range: 15–60 ng/L). The patient did nothave any history of neck surgery or radiation exposure thatcould have led to hypoparathyroidism. Other laboratory testson the serum showed urea nitrogen: 30mg/dL, creatinine:2.5mg/dL, albumin: 4.2 g/dL, sodium: 138mEq/L, potassium:3.9mEq/L, and magnesium: 1.65mg/dL (normal range: 1.6–2.3mg/dL). Urine volume in 24 hours was 1700mL withurine creatinine, protein, and calcium levels of 1020mg/dL,2 Case Reports in NephrologyTable 1: Comparison of presentation for patients with HDR syndrome.References Symptoms Heredity Number of patientsShaw et al. [5] Hypoparathyroidism, renal failure, anddevelopmental delay Autosomal recessive 2 girls and 2 boysBilous et al. [1] Deafness, hypoparathyroidism, and renaldysplasia Autosomal dominant 2 sisters and 2 brothersHasegawa et al. [7] Deafness, hypoparathyroidism, and renaldysplasia Autosomal dominant 1 girlWatanabe et al. [8] Deafness, hypoparathyroidism, andwithout renal disease Autosomal dominantOne-month-old infant and5 members of familyFujimoto et al. [9]Deafness, hypoparathyroidism, renaldysplasia, and recurrent infarcts in basalganglia— 1 boyMuroya et al. [4] Deafness, hypoparathyroidism, and renaldysplasia Autosomal dominant 9 patientsAksoylar et al. [10] Deafness, hypoparathyroidism, renaldysplasia, and psoriasis Autosomal dominant An 18-year-old girlKato et al. [11]Deafness, hypoparathyroidism, renaldysplasia, nephrocalcinosis, and renaltubular acidosisAutosomal dominant A 34-year-old womanTaslipinar et al. [12] Deafness, hypoparathyroidism, renaldysplasia, and renal tubular acidosis Autosomal dominant A 19-year-old manFigure 1: Electrocardiography showed a prolonged QT interval(560msec).176mg/dL, and 20mg/dL. Erythrocyte sedimentation ratewas 51 in the first hour and serumC-reactive protein level was18mg/dL. Serum protein electrophoresis was normal. Elec-trocardiography showed a prolonged QT interval (560 msec)(Figure 1).Noncontrast computed tomography of the brain showedintracranial calcification involving the basal ganglia, thala-mus, and cerebral cortex on both the right and left sides(Figure 2). Pure tone audiometry showed bilateral moderate-to-severe hearing loss that was more severe at the higher endof the frequency spectrum (Figure 3). Abdominal ultrasonog-raphy revealed a reduction in size of both kidneys (80mmin length) with an increased cortical echogenicity. Becauseof the simultaneous occurrence of hypoparathyroidism, deaf-ness, and renal disease, the patient was diagnosed with HDRsyndrome. However, chromosomal study of the patient usingstandard trypsin G-banding analysis showed no abnormality.The patient was administered calcium carbonate, ergocal-ciferol, and rocaltrol. After the sizures were controlled, he wasdischarged and is being followed up.3. DiscussionBarakat syndrome can occur at any age, and patients with thissyndrome usually show symptoms related to hypocalcemia. Itwas first reported in 1977 by Barakat et al. [2]. In 1992, Bilouset al. [1] described two brothers and two daughters of one ofthe affected brotherswith hypoparathyroidism, sensorineuraldeafness, and renal dysplasia. Subsequently, other reportsappeared in the literature confirming that the syndrome isassociated with a wide phenotype spectrum, consisting ofhypoparathyroidism, sensorineural deafness, and renal dis-ease [4, 7, 9, 13, 14]. Patients may present with hypocalcemia,tetany, or afebrile convulsions at any age. Hearing loss isusually bilateral (but may be asymmetric) and may rangefrom mild to profound impairment, being more severe atthe higher end of the frequency spectrum. Renal diseasesin these patients include nephrotic syndrome, cystic kidney,renal dysplasia, hypoplasia or aplasia, pelvicalyceal defor-mity, vesicoureteral reflux, chronic renal failure, hematuria,proteinuria, and renal scarring [1, 2, 11, 15–17]. However,most patients show progression to chronic renal failureand require renal replacement therapy [4]. Our patient hadchronic renal insufficiency. No renal dysplasia was detectedon imaging studies. Deafness is a consistent feature of HDRsyndrome. HDR patients have been reported to experiencebilateral sensorineural deafness, which is more severe athigher frequencies [18]. Our patient also showed similarfeatures on PTA.The original patients described by Barakat et al. [2] pre-sented with hypocalcemia and proteinuria, which progressedto a steroid resistant nephrotic syndrome, as well as withhypoparathyroidism and bilateral nerve deafness. Renal his-tology revealed fetal-like glomeruli and thickened glomerularCase Reports in Nephrology 3(a) (b)Figure 2:Noncontrast computed tomography of the brain showed intracranial calcification involving the basal ganglia, thalamus, and cerebralcortex on both the right (b) and left (a) sides.020406080100120125 250 500 1k 2k 4k 8k(Hz)Left earHL (dB)(a)020406080100120125 250 500 1k 2k 4k 8k(Hz)Right earHL (dB)(b)Figure 3: Pure tone audiometry showed bilateral moderate-to-severe hearing loss.basementmembranes.The parathyroid glands were absent orfibrotic. All four siblings died with end-stage renal diseasebetween the ages of 3 and 8. The patients reported by Bilouset al. [1] had bilateral renal dysplasia. Hasegawa et al. [7]found reports of 14 patients with deletion of 10p13; fivehad hypoparathyroidism or hypocalcemia, 6 had urinarytract abnormalities, and 2 had deafness. Fujimoto et al. [9]reported a Japanese boy with associated recurrent cerebralinfarctions in the basal ganglia. Lichtner et al. [15] performedmolecular deletion analysis of two patients with partialmonosomy 10p and hypoparathyroidism, deafness and renaldysplasia, or renal insufficiency, cardiac defect, cleft palate,and reduced T-cell levels. Table 1 showed characteristics ofthe reported cases of patients with HDR syndrome in theliterature.Diagnosis is based on the clinical finding. Diagnosis ofsuspected patients may be assisted by the following tests:measurement of PTH levels, an audiogram or auditory brainstem response study, renal imaging studies, and a renalbiopsy. DNA analysis may demonstrate the presence of a sub-microscopic deletion on chromosome 10p. Detailed studyof chromosome 10p should be undertaken in patients with4 Case Reports in Nephrologywell-defined renal tract abnormality phenotypes, especiallywhen there is associated hypoparathyroidism or deafness [3].Various combinations of this syndrome have been reportedincluding familial idiopathic hypoparathyroidism and pro-gressive sensorineural deafness without renal disease [6,8] and autosomal recessive hypoparathyroidism with renalinsufficiency and developmental delay [5]. Treatment con-sists of treating the clinical abnormalities associated withhypoparathyroidism, deafness, and renal disease at the timeof diagnosis. Prognosis depends on the nature and severity ofthe renal disease.Based on the findings of the present case, it is highly rec-ommended that, in the patients presenting with seizure asso-ciated with deafness, performing audiometry, calcium, phos-phate, parathyroid hormone determination, and renal imag-ing, studies can probably reveal this extremely rare geneticdisorder of Barakat syndrome.References[1] R. W. Bilous, G. Murty, D. B. Parkinson et al., “Brief report:autosomal dominant familial hypoparathyroidism, sensorineu-ral deafness, and renal dysplasia,” The New England Journal ofMedicine, vol. 327, no. 15, pp. 1069–1074, 1992.[2] A. Y. Barakat, J. B.D’Albora,M.M.Martin, andP.A. Jose, “Fami-lial nephrosis, nerve deafness, and hypoparathyroidism,” Jour-nal of Pediatrics, vol. 91, no. 1, pp. 61–64, 1977.[3] H. van Esch, P. Groenen, M. A. Nesbit et al., “GATA3 haplo-insufficiency causes human HDR syndrome,” Nature, vol. 406,no. 6794, pp. 419–422, 2000.[4] K.Muroya, T.Hasegawa, Y. Ito et al., “GATA3 abnormalities andthe phenotypic spectrumofHDR syndrome,” Journal ofMedicalGenetics, vol. 38, no. 6, pp. 374–380, 2001.[5] N. J. Shaw, D. Haigh, G. T. Lealmann, G. Karbani, J. T. Brock-lebank, and M. J. Dillon, “Autosomal recessive hypoparathy-roidism with renal insufficiency and developmental delay,”Archives of Disease in Childhood, vol. 66, no. 10, pp. 1191–1194,1991.[6] S. Yumita, Y. Furukawa, H. E. Sohn, H. Unakami, R. Miura,andK. Yoshinaga, “Familial idiopathic hypoparathyroidism andprogressive sensorineural deafness,” Tohoku Journal of Experi-mental Medicine, vol. 148, no. 2, pp. 135–141, 1986.[7] T.Hasegawa, Y.Hasegawa, T. Aso et al., “HDR syndrome (hypo-parathyroidism, sensorineural deafness, renal dysplasia) asso-ciated with del(10)(p13),” American Journal of Medical Genetics,vol. 73, no. 4, pp. 416–418, 1997.[8] T. Watanabe, H. Mochizuki, N. Kohda et al., “Autosomal dom-inant familial hypoparathyroidism and sensorineural deafnesswithout renal dysplasia,”European Journal of Endocrinology, vol.139, no. 6, pp. 631–634, 1998.[9] S. Fujimoto, K. Yokochi, H.Morikawa et al., “Recurrent cerebralinfarctions and del(10)(p14p15.1) de novo in HDR (hypopara-thyroidism, sensorineural deafness, renal dysplasia) syndrome,”American Journal ofMedical Genetics, vol. 86, no. 5, pp. 427–429,1999.[10] S. Aksoylar, Y. Aydinok, E. Serdarogˇlu, M. C¸oker, F. O¨zdemir,and F. O¨zkinay, “HDR (hypoparathyroidism, sensorineural dea-fness, renal dysplasia) syndrome presenting with hypocal-cemia-induced generalized psoriasis,” Journal of PediatricEndocrinology andMetabolism, vol. 17, no. 7, pp. 1031–1034, 2004.[11] Y. Kato, N. Wada, A. Numata, and H. Kakizaki, “Case of hypo-parathyroidism, deafness and renal dysplasia (HDR) syndromeassociated with nephrocalcinosis and distal renal tubular acido-sis,” International Journal of Urology, vol. 14, no. 5, pp. 440–442,2007.[12] A. Taslipinar, L. Kebapcilar, M. Kutlu et al., “HDR syndrome(hypoparathyroidism, sensorineural deafness and renal disease)accompanied by renal tubular acidosis and endocrine abnor-malities,” Internal Medicine, vol. 47, no. 11, pp. 1003–1007, 2008.[13] T. Hasigawa, Quoted in Online Mendelian Inheritance in Man,Personal communication, Johns Hopkins University #146255,1998.[14] M. A. Nesbit, M. R. Bowl, B. Harding et al., “Characterization ofGATA3 mutations in the hypoparathyroidism, deafness, andrenal dysplasia (HDR) syndrome,” Journal of Biological Chem-istry, vol. 279, no. 21, pp. 22624–22634, 2004.[15] P. Lichtner, R. Ko¨nig, T. Hasegawa, H. van Esch, T. Meitinger,and S. Schuffenhauer, “AnHDR (hypoparathyroidism, deafness,renal dysplasia) syndrome locus maps distal to the DiGeorgesyndrome region on 10p13/14,” Journal of Medical Genetics, vol.37, no. 1, pp. 33–37, 2000.[16] G. Ranjbar-Omrani, N. Zamiri, B. Sabayan, and A. Moham-madzadeh, “Concomitant hypoparathyroidism, sensorineuraldeafness, and renal agenesis: a case of Barakat syndrome,”Archives of Iranian Medicine, vol. 11, no. 3, pp. 337–340, 2008.[17] M. A. Sepahi, B. Baraty, and F. K. Shooshtary, “HDR syndrome(hypoparathyroidism, sensorineural deafness and renal disease)accompanied by hirschsprung disease,” Iranian Journal of Pedi-atrics, vol. 20, no. 1, pp. 123–126, 2010.[18] M. A. J. van Looij, H. Meijers-Heijboer, R. Beetz et al., “Char-acteristics of hearing loss in HDR (hypoparathyroidism, sen-sorineural deafness, renal dysplasia) syndrome,” Audiology andNeurotology, vol. 11, no. 6, pp. 373–379, 2006.

Seizure, Deafness, and Renal Failure: A Case of

Barakat Syndrome

Barakat syndrome (also known as HDR syndrome) is an autosomal dominant disorder characterized by hypoparathyroidism, sensorineural deafness, and renal disease caused by mutation of the GATA3 gene located at chromosome 10p15. The exact prevalence of this disorder is not known but is very rare, with only about a dozen cases reported in the literature. Here, we report a case of 58-year-old man from Ardabil who presented with seizure due to hypocalcemia. Further history revealed bilateral deafness. Audiogram confirmed sensorineural hearing loss of both sides. His laboratory data were consistent with hypoparathyroidism and renal failure. He was diagnosed to have Barakat syndrome based on his clinical and laboratory data. In conclusion, we need to be aware of rare inherited conditions in a patient with abnormal physical and laboratory findings even though their initial presentation was seizure and hypocalcemia.</jats:p

Nasrollah Maleki

Bahman Bashardoust

Manouchehr Iranparvar Alamdari

Zahra Tavosi

Crossref

Seizure, Deafness, and Renal Failure: A Case of Barakat Syndrome

Barakat syndrome (also known as HDR syndrome) is an autosomal dominant disorder characterized by hypoparathyroidism, sensorineural deafness, and renal disease caused by mutation of the GATA3 gene located at chromosome 10p15. The exact prevalence of this disorder is not known but is very rare, with only about a dozen cases reported in the literature. Here, we report a case of 58-year-old man from Ardabil who presented with seizure due to hypocalcemia. Further history  revealed  bilateral deafness. Audiogram confirmed sensorineural hearing loss of both sides. His laboratory data were consistent with hypoparathyroidism and renal failure. He was diagnosed to have Barakat syndrome based on his clinical and laboratory data. In conclusion, we need to be aware of rare inherited conditions in a patient with abnormal physical and laboratory findings even though their initial presentation was seizure and hypocalcemia

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andS.Schuffenhauer,“AnHDR(hypoparathyroidism,deafness, renal dysplasia) syndrome locus maps distal to the DiGeorge syndrome region on

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Seizure, Deafness, and Renal Failure: A Case of Barakat Syndrome

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