PAEDIATRIC NEPHROLOGY IOURNAT OF BANGLADESH Volume 3 Number 1 |une - - PDF document

SLIDE 1

JUNE 2018

I UI'UI I

I

• vol. 03
• NO. 01

SLIDE 2

PAEDIATRIC NEPHROLOGY IOURNAT OF BANGLADESH

Volume 3 Number 1 |une 2018 Editorial

• Dissemination of Paediatric Nephrology Service- A Demand of Time
• Prof. Mt|. Habibur Raltman

Original Articles

.

Pattern of Histopathology of Glomerulonephritis in the Department of Pediatric Nephrologv of A Tertiary Care Hospital: An Experience of Four Years Mohnnrmed Maruf-ul-QtLader, Kirity Prssad Deb, Sanot Kumar Bsrua, lmrul Kayes,

Bssana Rani Mulruri, \lasir Uddin Mqlmtrd, Prsnob Ktnnnr Choutdlrury, Arup Duttn, Klmli d S aifull ah, Aditi Choio dhu ry

• Study of Etiological Profile of Children Presented with Hepatomegaly andf or

Splenomegal,v: An Experience from Pediatric Gastroenterologv Department Bangabandhu Sheikh Mujib Medical University

• Md. Benzomin, Mtirutmn Sayeed, Md. Saidul Isloru, Rubttiyat Alam, Md. Ruktrnuzzaman,
• Md. Wahidttzzanlan Mnzumder, ASM Bazlul Karim

. Estimation of Serum IgG ler.el in Nephrotic Children with Infection

Sainta Ensin, Fsreln lesmin Rabbi, Shireen Afroz, Md. Anit,ar Hossnin KlMn

Review Articles

. IgA Nephropathy: A Rerrien

Ssbinn Sultantt, Afroza Begunr

• Recombinant Erythropoietin Therapr, In Children With Renal Anaemia : A Revier,v

Azmeri Sultarto, Ronjit Ronjan Roy, Golsrn Muinuddin, Md. Hnbibttr Raltnttn

• Nephrocalcinosis in Children: A Revier,r,

Fttrhttna Ralunan. Shsnnin Akter Luno,'I-ilnnins lesntin, Ranjit Ranjon Rou Case Reports

• Aerophagia in Children: Report of a Rare Functional Gastrointestinal Disorder

r,r ith Literature Rer ier.t

Wslritluzzorrtan Moiunttle r, Afstutri Yosmifi, Zatnmtul Fertlons Sonin, Fnlunitln Begutri,

Rtfu sitl s t A l nr rt, NILI. Rt Lk u r r u z z t r t t n n, A S lt4 B nzl ul Ks ri nt

• Svstemic Lupus Erythgrl.,.sus Presentirrg as Steroid Ilesistant Nephrotic Syndrome

A Rare Errent

lnlrortartr Arjtt, Rutnnrsns Tnzio,, Taltnittti Jcsnin, Ronjit Rartjnn Rotl

• Bowing of Leg ancl Cvnaeconrastia as an Atvpical Presentation of \{ilson Disease:

18 23 31 .)d

,18

51

• .A Case Report

' Md. Banzarnin, ASM Bazlul Karim, Rubaiqot Alam, Rijoq Talukder

A.fsnn n Y o.sntin, Ab dillahel Am anrt, 55

SLIDE 3

Cqse Report

Bowin g of L.g and Gynaecomastia as an Atypical Presentation of Wilson Disease: A Case Report

• Md. Benzaminl, -{S\I Bazlul Karim2, Afsana Yasmin3, Abdullahel Amaan4,

Rubaivat,\lami. Bij ov Talukder6

Akact

l\71*,n di*i.<e is an autosomal-recessizte disorder of chronic copper toxicosis due to mutation in

theATPTB gne-,thidt causesirnpairedbiliary copper excretion resultinginhEatic copper accumulation €- toicifu rnd subsequmt multisystem disease inaoloing the lioer, brain, cornea, skeleton and rarely the ]uart. The disease typically begins with an asymptomatic period zuith subclinical hepatitis and pros'resses to lieer cinhosis and neuropsychiatric symptoms, It may present with some unusual {eature, ulich sometimes confuses clinicians and makes a diagnostic dilemma. Here we present an 1"5 vears old bou presenfing with Bowing of leg and gynaecomastia diagnosed as Wilson disease.

Keywoils: Wlson disease, Bouting of leg, gynaecomastia. Introduction: Wilson disease (WD) is a rare autosomal recessive

disorder of copper metabolism. It was first described in 1912bv Kinnear Wilson as "progressive lenticular

de generation, " a tar:.rilial, lethal neurolo gical disease

accompanied by chronic liver disease leading to cirrhosis.l It affecb 1 in 30,000 peopie with a gene frequency of 0.56% &. a carrier frequency of 1 in 90.2 In some

populations living in socio-culturally isolated

comrrrunities n'ith a high rate of consanguinity, the frequencv of the disease is higher and may increase up to 1:1130.3

Wilson disease (WD) is a disease of copper

metabolism caused by mutations within the ATPTB

gene whichcauses impaired biliary copper excretion resuJting in hepatic copper accumulation & toxicity

1,. Resident, Phase B, Department of Paediatric Gastro-

enterologr" and Nutrition, BSMMU, Dhaka

• 2. Chairman, Depaftment of Paediatric, Gastroenterology

and Nuirition, BSMMU, Dhaka

3.

MD, Department of Paediatric Gastroenterology and Nutritioru BSMMU, Dhaka

4.

Residerrt, Phase B, Departrnent of Neonatology, BSMMU,

Shahbag Dhaka.

• 5. Medical olficer, Department of

Paediatric Gastroenterology and Nutritioru BSMMU, Dhaka

• 6. MD (2spart ), Department of Paediatrics, Rajshahi

Medical college Correspondence: Dr.Md. Benzamin , Resident, Department

• f Paediatric Gastroenterology and NutritioO BSMMU, Dhaka

Shahbag, Dhaka, Mobile no: 01,7L9183948, E-mail: drmd. benzamin@yahoo.com

(Paed. Neph. l. Bang. 2018; 3(1) : 55-59).

and subsequent multisystem disease involving the liver, brair; cornea, skeleton and rarely the heart.a

Case Report 15 year old boy,ltt issue of non-consanguineous

parents presented with the history of bowing of leg & difficulty in walking for last 2 years,enlargement

• f breast for last L year & slurring of speech for last 6
• months. Bowing of both leg initially was mild which

gradually increasing associated with progressive walking difficulty.

Mother noticed gradual enlargement of his breast like

• female. For last 6 month he developed dysarthria in

the form of slurring & is progressive. Mother also noticed abnormal body movement for last 6 month.

Mother give history of deterioration of school

performance for last 3 years & fracture of sha-ft of tibia (right) following minor trauma'l.year back. He had no history of jaundice, joint pain & convulsion .He hadfamilyhistory of death due to liver disease; others member are healthy. Hehadno H/Oimmunization against Hepatitis B. He received inj. testosterone for g)maecomastia. On examinatior; he has smiling face,

afebrile, moderately pale, anicteric and vitally

stable.Wasting of thenar & hypothenar muscle, true g)maecomastia present,no pubic hair or axillaryhair. His height was 149 cm & weight 33 kg -within centile. On gastrointestinal sytem examination, just palpable

liver, splenomegaly 3 cm & ascites present evidence by shifting dullness . on nurological examination incordination of movement,dysarthria & brisk knee

jerk present.on locomotor examinatiorL joint normal & intercondyler distance L0 cm.

SLIDE 4

• Paed. Neph. J. Bang.

Complete blood count shows moderate anemia thrombocytopenia, serum albumin low,SGpT high, 25-OH vit-D low, s.creatinine, s.uric acid normal, prothrombin time with NR -high, USG of HBS shows

coarse hepatic parenchyma with splenomegaly with

ascites (Table I). After evaluating the clinical data, physical findings and investigations results, the case was provisionally diagnosed Chronic liver disease

due to Wilson disease with Rickets. As patient is not

immunized against HBV we had a differential

diagnosis - Chronic liver disease due to chronic Hepatitis B with Rickets.After evaluating the patien/s

presenting features, physical findings ind the

laboratory tests results, s.ceruloplasmin (6mg/dI ), 24 hour urinary copper (374 micro grn/ dI) ,eye evaluation for K-F ring ( +ve) was done which ill

goes infavour of Wilson disease.

HBsAg & anti HCV was negative which exclude viral

cause of CLD. We also did esophago-gastroduodeno- scopy which shows esophageal varices. For bowing of leg we gone for xray lower limb & there

was no feature suggestive of rickets expect generalized osteopenia .S. Vitamine D was

low(insufficient) but S.C6++, Alkaline phosphatase

,S. PTH was normal. Dexa bone scane for bone marrow

density was done & shows reduced bone mineral density .MRI of brain suggestive of Wilson disease.

7Ro/,ll

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• Vol. 03, \o

Table-I

Lab or atory intt e sti

t tt t i u t

Investigations Patient's I'a1ue Hemoglobin White cell count Neutrbphil Lymphoryte Eosinophil Monoryte Platelate

ESR PBF

S.Albumin Prot}rombintime

SGPT

25-OHvit-D

UrineR/M/E

S.creatinine S.electrolytes S.uric acid DopplerUSGof HBS

c

Fig:a.SnilingfncezuitltLtotttingoflegb Generalizedosteopenioc.Htllteriltertsesignalclwr.tgesinlentiforxtnucleus.

56

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SLIDE 5

• Md. Benzamin et al

Table-II

Ittbar atory ino esti g ations

ht es:ri,:: - :---

Referencevalue S.cc'rlti.,:,.ts::' :-

2-1 hor-rrs urlr-ar., - - : --

Ereeralu.rr..:'-' : -

r

HBsAg

AntiHC\

Ent1oscr.1.,. :.- l- Xravbtr:l- -.:

• --

Alkail'-:-- --- . -.

S.C;r--

S.PT}.

B\lD : - ,- --

trf.rr. ; -l

\Ilit.,--

_. 6mg/dl

37{microgm/d

hesent \egative \egative

Grade Itr Oesophageal varices

Csreralized osteopenia; no features of rickets 20-60mg/dl

less than 60 micro gm/ d

?rJ0u/L

30_120 U/L

9ng/dl

77.15 pg/ml 9.0_80 pglml lu-rnber 1st to 4ft vertebrae -4.zRight femoral neck -Sleft femorll ne ck -4.2 E:.ateral svmmetrical T2WI &FLAIR hyperintense signal changes in lentiform

nlrcleus ,a1so in paraventricular & sub cortical white matter -suggestive of We also done rarnilr- screening, younger brother of case shorss lorr ceruloplasmin 6 , normal ALT,

significant urinan copper(259 mic gm/day) & K-F ring on both e.r-e. But as he was asymptomatic. According to the history, physical examination,

investig"aticrn . it n-as the case of Chronic liver disease due to I\-ilson di-ase with neurological invovement

with osteomalacia rrith portal hypertension.

Wilson di-cea-.e is an autosomal-recessive disorder of chronic copiper toxicosb. It is caused by mutation in

theATEB gene. rrhich is located within 13q14-q21

• n chromcrsome Li. It results in the impairment of

billiarv €rcr€tirafl of copper and subsequent

accumulation of it in rariuos tissues, initially in the

• liver. 5,6 SutsequEntlr-. rr hen hepatic storage capacity

for coppe.r bcolnt** sarhrrated, circulatory,fr"" "opp"i, level is increa-.si and deposited in various organs, notablv the t'rain i<idner s, and comea.T The clinical rta:-Lilstafioruc of Wilson disease usually are related to the hepatic or CNS involvement. The presenting teatuls are variable, and clinical disease is rareh- preer: hetore 5 r-ears of age. In the series of

Scheint'ere an"j Sternlib (1984), the initial clinical maniiestatitrns 11 ere hepatic in 42% of patients, neurologic in il'. . psr-chiatric ln 10%, hematologic

• r endcrrfu'rologicai in 12'i, and renal in 1%.8 In

children the,ll-ase usuallr- presents after 3 years of

age u'ith eitherincidental discovery of abnormal liver

function tesls or as chronic liver disease and rarely

as aqute hepatic i-ailure. 9

metabolic liver disease ,most likely Wilson disease .

Our patient having the feature of both hepatic, neurological and endocrine involvement like

stigmata of chronic lirrer disease, hepato-

splenomegaly, dysarthia,deterioration of school

performance, smiling face, gynocomastia and delayed puberty.

Various other presentations mav be there in Wilson Disease, including- neuropsychiatric disorder, Coombs negative hemolytic anemia, gall stone formation, cardiac inr.olvement, ovarian dvsfunctiory

hypoparathyroidism, renal tubuiar lesion and

subsequent renal calculi. Some osseomuscular defect

with botrv deformitv, spontaneous fracture and

arthropathv are also seen. KF rings are found in 50_ 60?6 cases vl,ithout treurological sr.mptoms.t0

Occassionallr, these patients develop some atvpicalnfeatures, r,r,hich procluces cli;rgnostic

d ilemmas.l'u

In addition, several author.s hal.e noted its association w,ith muscuIoskeleta1 intpainlents, and among the various i urp;rirn-r ents clcscri becl, deminera liza tior.: is

found to be the rnost prirrciplet involrremerl. 11'13 16"

plevaletrce of osteoper-iia and osteoporosis in children

r,r,ith WD rv as f o und a s 22.6,) ; ancl 67 .7 ol, respectit.elv.

BMD and BMC levels \,vere higher irr childre.n rr ith

neurol o5;ic involr,ement.l+ Our patient presented r,r,ith musculoskeletal feature

that is bowing of leg ancl r,t alking difficultr.. This bowing of 1eg due to steomlacia supported bv X-rar.

and bone rnineral density (BN4D) Z score. 57

SLIDE 6

• Paed. Neph. J. Bang
• Vol. 03, No. 01, June 2018

Table III

Leipzig score: Diagnostic Scoring SystemforWp ts Biochemistry Score

Clinical symptoms and signs

Score

Liver copper content(in the

absence of cholestasis)

Normal (<50 pglgof dryweight)

<5 times ULN (50-250 pglg of dry weight) >5 timesULN (>250 tglgof dryweight)

Rhodanine stain absent present Serum ceruloplasmin Normal (>20mg/dL)

10-20m9/dL <10rng/dL Dai$ urinary copper excretion Normal 1-2timesULN >2timesULN Normal but >5 times ULN after pCT

Coomb's ne gatir.e hernolytic anemia

Absent Present

+1

Neuropsvchiatric svmptoms suggestive of WD

andf or tvpical brain magnetic resonance imaging

KI rings

Absent Present Absent

Mitd

Severe ATPTB genetic anaiysis'

Nomutationfound Mutation on one chromosome Mutations on both chromosomes

+2

• 7

+1 +2 +1 +1 +2 +1 +2 +1

+2 +2

+1 +4

Due to difficulty in diagnosing Wilson disease, a scoring system was created and promoted by the gth International meeting on Wilson disease which is based on seven criteria, including the presence of

Kayser-Flesicher rings; typical neurological symptoms; decreased serum ceruloplasmin

concentration; Coombs' negative hemolytic anemia; elevated urinary copper excretion; high liver copper value in the absence of cholestasis and mutational

• findings. Like all other laboratory testing this scoring

system tends to be more reliable in patients with advanced disease .15 A score e,, 4 indicates that

disease is highly likely; a score of 2 or 3 indicates that disease is probable and further investigations are needed, and a score of 0 or 1 indicates that disease is

unlikely.l6 Our patient's Leipzig score was Z that is Serum ceruloplasmin < 10mg/dl, Daily urinary copper excretion >2 times of upper limit, K-F ring present, mild neuropsychiatric symptoms suggestive of \AID

and typical brain magnetic resonance imaging. 58 Treatment of Wilson disease is copper diet and copper

• chelator. In 1951, Denny-Brown and porter and

Cuntngs inh-ocluced clirnercaprol(BAL) as an effectir.e treatment of \\-ilson disease. But tire e-laih, oainful intramuscular injection= nta.1e B.\L inr;.r3.ii.u1. rr.,

1956, D-penicillamtre rr a. iir:: u:e!-1 as an effective

alternative treatrtrer,.: :o: \\-i-str s .lisease. other,s

treatment inclu.le Trren:i:,e. Ztnc , Tetrathio_

molvbdate, Lir-er transp.la.'..:ation , Genetic therapy

and hepatoct'te trans':i ai-1, -.ior.t. r. -13 Our patient \\'ere treaieri rr ith copper free diet, zinc,

D-penicillanrine an.1 p r sp 1anoIo1. D-penicillamine can cause u'orsenjlq of neurologic Wilson disease in 10;"/"-50'" cases.ll ll In a recent series, neurologic worsening occurrecl on all three treatments used for Wilson's disease 1 D -penicillamine, trient ine, zinc), but mainh'rr-ith D-penicillamine, where 13.g% were

• adverselr. alfectecl 16

Trientine is not ar.ailable in our country. That,s why

D- penicillamrre given with proper monitoring.

SLIDE 7

Bo*i'Lg oi Leg ancl Gl'n.lecomastia as an Atl,pical presentation of wilson Disease

Conclusion Wilson disease is a multisystem involving disease and it has a variable clinical presentation. It may present as asymptomatic elevated ALT to liver

cirrhosis, neurological and neuropsychiatric

• manifestation. Atypical feature like musculoskeletal

and endocrine symptoms may give a clue for Wilson

• disease. Early diagnosis and treatrnent is an important

factor for better prognosis. References

1.

Wilson, SAK. 'Progressive lenticular degeneration: a farnilial nen'ous disease associated with cirrhosis of the

lir.er', Brain, 7972; A: 295-209. 2.

Scheinberg IH, Sternlieb I, Schilsky M & Stockert RJ. 'Penicillamine may detoxify copper in Wilson,s disease,, Lancet, 1987;2:95.

3.

Coco' R =endroiu A, Schipor S, Bohilpea LC, ,endroiu I Raicu F. C-,enohpe-.Phenotype Correlations in a Mountain Popml66orl aool-unih. with High prevalence of Wilson,s

Di.-ase C*netic and Clinical Homogeneity. pLoS ONE

1014; 9i6t: e98520. https://doi.org/10.1J21/

i ournai- pone. l1O98 52 0

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BunL PC. Thomas. GR, Rommens, M, Forbes, ]R & Cox,

D1{. 'The l{ilson disease gene is a putative copper

P-trpe ATpase similar to the Menkes gene,,

\ature C,sretics, 7993; 5: 327-927. 5.

Roterts E{" fthlsk\- ML. Diagnosis and treatment of \fiLson dl-ease: an update. Hepatoiogy. 200g;42:20g9_

2111 "

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Dzierc K. I-itrsin T, Czonkowska A. Other organ inroh-ement and clinical aspects of Wilson disease.

Handtec,k ot Cinical Neurology, 2017;142: 2_24g.

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Rir-az -{- ltll<sr"s rlisa<e. nL Riyaz A, editor. pediatric

Castroent€.olry1- and Hepatology. Hyderabad, New Delhi: Fara-< I{e*iical publisher; 2009. 551_68.

8.

l\ilson-s .ijr-ea_<e la rolume in the major problems in internal me.licine series) Bv I. H. Scheinberg and I.

Sternliet^ Fldialelphia_ I!-. B. Saunders, 19g4

• Md. Benzamin et al
• L2. Golding DN, Walshe JM. Arthropathv o{ Wilson,s
• clisease. Stuclr, of clinical and racliological features in 32
• patients. Ann Rheum Dis. 1977; 36: 99_111.
• 13. Feller ER, Schur.nacher HR. Osteoarticular changes in

\,Vilson's dise.rse. Arthritis Ilheurn. 1972; 73: 2b.)_266.

• 11. J. Clin. Gastr.oenterol. 2008Feb;42(2):194_g. doi:10.1097 /
• MCC. 0b01 3e31 8032388c-I.
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]oumal of Hepat6l6gy 20L2; 56: 671_685

• 16. Ferenci, P, Caca, K, Loudianos, G, Mieli_Vergani, G,

Tanner, S, Sternlieb, I et al. ,Diagnosis and phenotvpic classification of Wilson clisease,, Liver- Internatinal, 2003; 23:139-12.

17 . Walshe JM. 'Penicillamine, a neu. oral therapl,for Wilson,s

disease'. American Journal of Meclicirre, vol. 1956; 21,

• pp. 487-495.
• 18. Saito, H, Watanabe, K & Sahara, M. ,Trietl-rylene_

tctramine (trierrtinc) therapv for Wilson,s clisease,, Tohoku Journ.rl of Experimental Meclicine, iJ991l; 161,

29-15.

• 79. Santos SE, Sar.les J & Buts Jp. ,Successful rneclical treatment
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Pediatrics, 1996; 728: 285-2g7.

• 20. Hoogenraad TU, Koevoet Il & Korve, EG. .Oral zinc

sulphate as long-term treatment in Wilson,s clisease (hepatolenticular degeneration),, European Neurology, 7979; 18 205-27t,

21,. Hoogenraacl TU, Van HJ & Van, DHJ. ,Management of

Wilson's disease w.ith zinc sulphate. Erperience in a series

• f 27 patients', _lournal of Neurological Sciences, 19g7;

77:137-146.

22.

Brer,r.er GJ, Hedera p, Klein Kl & Carlson M. ,Treatment

• f Wilson's disease n ith ammonium tetrathiomolybdate.

Initial therapy in a total of 55 neurologically affectecl

patients arrd follow up with zinc ther.apy,, Archives of Neurology, 2003; 60: 279_385.

• 23. Teradak N & Yang XL ,Biliarv exertion of copper in rat

after introduction of copper trasportng ptype ATpase,, ATP febslch, 7999; 448: 5356.

• 21. Brewer GJ, Terry CA, Aisen AM, Hill GM. 19g7,

'Worsening o{ neurologic sr.ndrorne in patients vr,ith Wilson's disease rvith initial penicillamine t}.Lerapr,,, Archives of Neurology, 1987; 44:,+90_.193.

• 25. Walshe JM &Yealland M. ,Chelation treatment of

neurological Wilson's disease,. The euarterlr. Iournal of Medicine, L993; 86: 197-201.

• 26. Merle U, Schaefer M, Ferenci p, Stremu.Lel \\.. Clinical

Presentatiory diagnosis and long-term outcome of \Vilson disease - a cohort study. Gut 2007; 56:115_120.

9.

Dharr-an- -{" Tarlor, R\f. Cheeseman, p, De Silva, p, Katsir-iamakis. tr_ L\tieli-\rergani 2005,,Wilsons disease in chilrl.lruL Si-1-ear erperience arrd revised King,s score

tbr lirer tan:Flarltation'. Liver transplantation, 2005;

11; {t1-{45" Cors Pl" Srnallrscrod RA." Angus pW Smith AL, WaIl

Af, Serl-ell Rts- Diagnosis of Wilson,s Disease: An I{indelzun R- Elkin \I, Scheinberg IH, et al. Skeletal changs in lfi]lson's disease. A radiological study.,

Rafi ologl-. 1 9f t-)94:12i-132.

10.

L7. 59