Hereditary nephritis associated with low-tone. sensorineural hearing difficulty :A case report

Transcription

1 Hereditary nephritis associated with low-tone sensorineural hearing difficulty :A case report Medicine, and ***Second Department Pathology, Toho University School Medicine, Tokyo, Japan ****Department Pediatrics, Kitasato University School Medicine, Sagamihara, Japan findings by immunluorescent ear hearing difficulty. Audiogram her brother revealed also low-tone sensorineural sensorineural familial low-tone hearing difficulty has not been reported previously Infoduetion Presentation This is a report rare one family with Alport syndrome, they showed hematuria, proteinuria and low tone sensorineural hearing loss. Although Alport syndrome is accompanied by hereditary nephritis, high-tone sensorineural hearing loss and eye involvement, low-tone sensorineural hearing loss like in this family is not reported thus far. noticed at 13-year-old Accepted January 24, 1996 Osamu MOTOYAMA, Masaaki OHSHIMA, Yukari SHIGETOMI, Takehiro OHARA*, Yohko NAGAI**, Sadao KAWAMURA***, and Kikuo IITAKA*** First Department Pediatrics, *Department Nephrology, **Second Department Internal The proband was a 14-year-old girl with hematuria and proteinuria. Many members her maternal pedigree had hematuria and proteinuria. Her mother, younger brother (age 12 years) and younger sister (age 9 years) had microscopic hematuria and proteinuria with normal renal function. Her mother had nephrotic syndrome during pregnancy and a renal biopsy was performed. Light microscopic findings the renal biopsy specimen revealed mild mesangial proliferation and irregularity glomerular basement membrane. The pedigree showed no chronic renal failure and no deafness. The proband had experienced microscopic hematuria and occasionally macroscopic hematuria since 3 years age. Proteinuria increased steadily and at the age 14 years, she had nephrotic syndrome and renal dysfunction (creatinine clearance 57.9ml/min/1.48m2). Renal biopsy was performed and light microscopic findings showed segmental mesangial cell proliferation and numerous interstitial foam cells without significant study. Electron microscopic examination showed splitting into many layers and thinning the glomerular basement membrane. She had no complaint hearing. However, audiological studies detected bilateral low-tone (from 125Hz to 1000Hz) sensorineural hearing difficulty, ranging from 30 to 40dB. High scores on the short increment sensitivity index (5151) test suggested inner hearing loss. Hereditary nephritis with the characteristic lesion the glomerular basement membrane and hearing difficulty has been known as Alport syndrome. Alport syndrome associated with. Jpn J Nephrol 38: ,1996 Key words: Alport syndrome, hereditary glomerulonephritis, low-tone sensorineural hearing loss Case A 14-year-old girl was admitted to because hematuria and proteinuria. The patient was found to have hematuria at the 3- year-old health check. Microscopic hematuria has been continued thereafter and occasionally macroscopic hematuria was found in infancy. Proteinuria started at the age 7. A slight decrease in serum albumin (3.0 g/dl) and increase in total cholesterol (239 mg/dl) were (August, 1993) with normal serum creatinine and proteinuria (206 mg/dl). In

2 234 Osamu Motoyama et al 1994, proteinuria increased and the patient was admitted to our hospital for biopsy and treatment nephrotic syndrome. There were no consanguineous marriage. Maternal grandfather and his brother had hematuria. The mother this patient was found nephrotic syndrome at the pregnancy the patient (primigravida), when proteinuria appeared from 17 weeks pregnancy and urine protein reached up to 8-10 g/day with serum TP 5.2 g/dl and albumin 2.6 g/dl. The patient was born at full term and her weight at birth was 2,900 g. There was no abnormality at her birth, when congenital hearing loss might be caused by various factors [2]. Biopsy the kidney her mother who still had proteinuria after delivery, was performed at 9th day after her delivery. Proliferative changes glomerulus were slight but irregular thickening and splitting at the basement membrane were found. The suspicion membranoproliferative glomerulonephritis was diagnosed. Her mother was discharged 1 month later from her birth, because her urine protein decreased about 1-2 g/day. Almost the same increase in urine protein was noticed at pregnancy second and third children. At present, her mother has only slight proteinuria (81 mg/dl) and microscopic hematuria. There were no evidence edema, hypertension, increase in serum creatinine and changes in complements. Her brother (12 y.o.) and sister (9 y.o.) were found to have hematuria at the 3 years old health check. Their hematuria continued thereafter and occasional proteinuria was noticed with normal BP and normal renal function. There are neither family history chronic renal failure nor hearing loss. Present illness at admission ( ): height 152cm (-0.6 SD), body weight 43 kg (-0.8 SD), blood pressure 110/70, chest and abdomen- normal, no edema, visual acuity 0.05 in both side (corrected visual acuity 1.2) without lens and fundus abnormality. Hearing difficulty is found by audiometer in low-frequency band ( Hz). There are no difference between air and bone conductivity. The internal ear hearing disturbance (low-tone sensorineural hearing difficulty) is diagnosed (the short increment sensitivity index test is 100% in right and 95% in left at 500 Hz). Her brother also has the same low-tone sensorineural hearing difficulty (Fig.2) although her sister is normal. Histological findings renal biopsy ( ): In light microscopy, one glomerulus was hyalinized out 6 glomeruli in the specimen. Other glomeruli had slight segmental mesangial proliferation and wall thinning. There were many foam cells in interstitium, and slight fibrosis was found around the hyalinized glomerulus (3 a,b). In IF, only fibrinogen was found in mesangial area slightly. In electron microscopy, there were evident thinning, waving, lamination, reticular changes basement membrane and fine granular Table 1. Laboratory data on admission 1. Pedigree. : death;,:normal urinalysis ;,: hematuria ;,: proteinuria; NS : nephrotic syndrome ; HL : low-tone hearing difficulty Bx : renal biopsy deposits were found in basement membrane ( 4 a, b). From these characteristic findings, Alport syndrome was diagnosed, even without the evidence type W collagen ƒ 5 chain. Discussion In 1927, Alport reported the hereditary nephritis with sensorineural hearing difficulty and thereafter eye involvement are also found to be accompanied by this syndrome. Therefore Alport syndrome is diagnosed with symptoms hereditary nephritis, sensorineural hearing difficulty and eye abnormality [1]. But for the

3 Nephritis with low-tone hearing loss 2. Audiograms 3a. Light microscopic findings mesangial cells. 4a. micrograph Electron characteristic membrane. formation mild at age 14 and brother at age 12 show hearing pattern low-tone loss. segmental proliferation (PAS; ~200). changes Foot show proband processes microvilli. lower splitting effacement ( ~3000) magnification the shows glomerular is also diffusely diffuse basement seen 3b. In the same cells are 4b. Electron glomerular with ( ~5000). observed. specimen micrography basement as 3a, numerous interstitial foam (PAS; ~200). shows membrane, splitting containing. into many small layers dense particles. the

4 236 Osamu Motoyama et al definite diagnosis, abnormal findings in electron microscopy (e.g. basement membrane splitting et al) is necessary [3], because various hereditary types and sporadic cases (about 20%). Recently, abnormality type W collagenƒ 5 gene (Xq22) was found in sex linked dominant Alport syndrome [4], and also changes in type W collagen a 3, 4 genes (chromosome 2) were found in autosomal recessive Alport syndrome [5]. In this case, because there is a family history nephritis, characteristic changes in basement membrane by electron microscopy, and sensorineural hearing loss ( also her brother has), Alport syndrome is diagnosed. The medical history her mother indicates also Alport syndrome with compatible evidence renal biopsy findings and proteinuria. Diagnostic criteria proposed by Flinter [6] includes high-tone sensorineural hearing difficulty and the cases reported thus far had high-tone hearing loss (rarely reported C5 dip with abnormality at 4000 Hz) [3]. 37 cases with hearing loss Alport syndrome reported by Habib [7], 3 cases with complete audiometer test reported by Johnsson [8], and 2 case Myers [9], had no low-tone hearing difficulty was included. Also Paolo [10] reported that hearing loss was started from high-tone area cleared by follow up audiometer test in 10 cases out 18 Alport syndrome. The causes hearing difficulty in Alport syndrome are thought to be vascular abnormality temporal artery and cochlea artery which is the same change in renal glomerular basement membrane [8,11]. However the case Alport syndrome with hearing difficulty but no structural abnormality in ears was also reported [9]. Also other factors like renal failure, dialysis, drugs (antibiotics, diuretics et al) may cause hearing loss and make obscure the pathological changes in ear structure [2]. Familial hearing difficulty with low-tone band usually is autosomal dominant [12], but the incidence is as low as 3-4%. There is no definite explanation which can explain the reason for difference between low and high tone hearing loss [2, 13]. In this paper, the reason why low-tone hearing loss with Alport syndrome occurs, is not cleared. In adult hemodialysis patients, we found bilateral low-tone hearing loss in 3 out 137 cases, but the causes chronic renal failure were not evident [14]. Prognosis Alport syndrome is thought to be better in female [1, 3, 7]. In Alport syndrome with X linked, female patient has one normal gene, therefore symptoms are much better than in male. We cannot identify the genetic transmission type from the pedigree this family, but symptom female is much severe in contrast to previous reports. From the survey hereditary nephritis in Japan, 58 cases Alport syndrome (male 38, female 20) were examined and the deterioration was much ten in female (17 times in 10 cases) than in male (21 times in 17 cases) [15]. The age deterioration (Ccr < 60 ml/min or Ccr < 20 ml/min) was 13.5 years old in female and 15 years old in male. Also in 24 families in hereditary nephritis, 14 out 36 cases female patients with persistent microhematuria and/or proteinuria became end-stage renal failure and 9 cases needed dialysis before 35 years old [16]. These surveys suggest that female patient with Alport syndrome might be poor prognosis like this family. In future, examination genetic analysis and phenotype changes in hereditary nephritis (Alport syndrome), might find out the definite abnormality in gene. Alport syndrome was divided into two groups which were one with hearing loss and another without hearing loss, but we think that it is important to account analyse types the hearing loss type (high-tone or low-tone) for evalution. Acknowledgement This case was reported in the 25th Eastern Meeting Japanese Society Nephrology held in Sendai, in may We greatly thanks to Pressor Makoto Oda in the department otolaryngology for advises audiometer test and hereditary hearing loss. Address to: Dr. Osamu Motoyama, First Department Pediatrics, Toho University School Medicine Omori-nishi, Ota-ku, Tokyo 143, Japan References 1. Alport AC: Hereditary familial congenital haemorrhagic nephritis. Brit Med J1: , Schukencht HF: Dominant hereditary sensorineural hearing loss. Pathology the ear (2nd ed). Lea & Febiger, Philadelphia, pp , Gubler MC, Habib R: Alport's syndrome. Pediatric nephrology (2nd ed); ed by Holliday M, Barratt TM, Vernier RL. Williams & Wilkins, Baltimore, pp , Antignac C, Knebelmann B, Drouot L, Gros F, Deschenes G, Hors-Cayla MC, Zhou J, Tryggvason K,Grunfeld JP, Broyer M, Gubler MC: Deletion in the COL4A5 collagen gene in X-linked Alport syndrome.(characterization the pathological transcripts in nonrenal cells and correlation with disease expression.) J Clin Invest 93: , Tryggvason K, Zhou J, Hostikka SL, Shows TB: Molecular genetics Abort syndrome. Kidney Int. 43: 38-44, Flinter F: Alport's syndrome. A clinical and genetic study. Hereditary nephritis. Contrib Nephrol vol. 80; ed by Sessa A, Meroni M, Battini G, Karger, Basel, pp9-19, Gubler M, Levy M, Broyer M, Naizot C, Gonzales G, Perrin D, Habib R: Alport's syndrome. A report 58 cases and a review the literature. Am J Med 70: , Johnsson LG, Arenberg IK: Cochlear abnormalities in Alport's syndrome. Arch Otolaryngol 107: , Myers GJ, Tyler HR: The etiology deafness in Alport's syndrome. Arch Otolaryngol 96: ,1972

5 Nephritis with low-tone hearing loss Arnold W: Consideration on the pathogenesis the cochleo-renal syndrome. Acta Otolarvngol 89: McKusick VA, Francomano CA, Antonarakis SE: Deafness, Progressive low-tone. Mendelian inheritance in man (vol. 1) (10th ed), Johns Hopkins University Press, Baltimore, pp301, Sasano T: Familial deafness showing hearing pattern low tone losses. Jpn J Otolaryngol 94: , Kusakari J, Kobayashi T, Rokugo M, Arakawa E, Kawamoto K: Hearing and vestibular function in the patients treated with hemodialysis. Jpn J Otolaryngol 84: , Uraoka Y, Akano N, Tooda M, Iseki T, Miyamoto H, Maki S: Survey on hereditary nephropathies (Special reference to Abort's svndrome). Jon J Nephrol 25: Grunfeld JP, Noel LH, Hafez S, Droz D: Renal prognosis in women with hereditary nephritis. Clin Nephrol 23: ,1985