University Journal of Medicine and Medical Specialities

ISSN 2455- 2852 2018, Vol. 4(4)

Intermediate Type Of Osteopetrosis - A Case Report THANGAVEL Department of Paediatrics,MADURAI MEDICAL COLLEGE AND HOSPITAL

Abstract : Osteopetrosis Refers To A Group Of Single Gene Left had painful restriction of Diseases Characterised By Generalised Sclerosis Of movements and deformity. Skeleton . We Had A Child Presented With Anaemia And INVESTIGATIONS Features Of Skeletal Dysplasia.He Diagnosed To Have Peripheral blood smear showed dimorphic anaemia with Intermediate Type Of Osteopetrosis With clinico radiological thrombocytopenia . evaluation. Serum calcium was 7.7 mg %(hypocalcemia) . Keyword :Osteopetrosis,Osteoclast ,Stem Cell,Autosomal. Serum alkaline phosphatase - 322 u/l(elevated) , Introduction : Serum lactate dehydrogenase – 1546 u/l(elevated) Osteopetrosis ( Marble , Albers- Schonberg Blood gas analysis showed uncompensated respiratory disease, Brittle bone disease) encompasses a group of highly alkalosis . heterogenous conditions ranging from asymptomatic to Ultrasound abdomen , Echocardiography and CT brain were severe form in which there is increased bone mass resulting normal . in characteristic phenotypic features such as altered cranio X RAY FINDINGS facial morphology ,cranial nerve compression , extramedullary 1.X RAY HAND - endobone formation (i.e) bone within bone haematopoiesis and anemia. appeance is seen.(fig 2) Epidemiology: 2. X RAY BOTH - vertical diaphyseal lucencies, The incidence of horizontal metaphyseal lucencies are 1. Autosomal dominant type is 1/20,000 births present.(fig 3) 2. Autosomal recessive type is 1/ 2,50,000 births 3. X RAY LEFT WTH ARM AP VIEW - transverse fracture of left humerus with callus formation is present.(fig 4) 4.XRAY VERTEBRAE - generalised increased is noted.(fig 5) 5.XRAY SKULL – Thickened base of the skull is present. Angle of mandible is normal.(fig 6)

Case summary : A 41/2 year old developmentally normal nd male child born to 2 degree consanguinous parents and who had an apparently normal elder sibling was brought with FIG 2 - XRAY HAND OF THE PATIENT the following complaints since 2 years of age. Mouth Showing classical BONE WITHIN BONE APPEARANCE breathing ,difficulty in walking ,frequent falling of teeth ,deviation of angle of mouth to left side ,abdominal distension and recurrent respiratory infections . On examination the child had dolicocephaly, oblique eye slant,nystagmus, micrognathia,protruded tongue, short neck , , cubitus varus,pot belly and . Vitals were sable . Anthropometry revealed short stature On systemic examination child had severe FIG 3 - XRAY BOTH OF THE PATIENT pallor ,hepatosplenomegaly, and right side lower motor Showing Horizontal striations - METAPHYSEAL LUCENCIES neuron type of facial palsy . Ophthalmological evaluation revealed optic atrophy secondary due to stenotic optic canal/ and vertical diaphyseal lucencies. due to osteopetrosis per se.

An Initiative of The Tamil Nadu Dr. M.G.R. Medical University University Journal of Medicine and Medical Specialities

Genetically 7 different types are present in autosomal recessive type whereas 2 types are present in autosomal dominant type .Some of the genetic mutations will have specific phenotypic features such as 1.Mental retardation (CLCN7,OSTM1,CA2) 2.Hypogammaglobulinemia( TCIRG1,OSTM1) 3.Cerebral calcification,Renal tubular acidosis ( CA 2). FIG 4 - XRAY LEFT SHOULDER AP VIEW OF THE PATIENT Rare variants are1. OLEDAID syndrome Showing PATHOLOGICAL FRACTURE OF HUMERUS WITH Ol – Osteopetrosis, Lymphedema : EDA- Anhydrotic CALLSU FORMATION Ectodermal Dysplasia Id – Immunodeficiency 2. Osteopetrosis with infantile axonal neuronopathy Clinical features Visual loss due to progressive bony encroachment on optic nerve,optic atrophy,primary retinal degeneration. Hearing loss - occurs due to bony compression of VII th cranial nerve,scelerosis of ossicles. FIG 5 XRAY SPINE LATERAL VIEW OF THE PATIENT Recurrent infections , failure to thrive Showing GENERALISED INCREASE IN BONE DENSITY Hypocalcemia,renal tubular acidosis Abnormal cranio facial appearance – , frontal bossing, Anaemia with hepatosplenomegaly Pulmonary hypertension Hydrocephalus ,neurodegeneration , seizures Choanal stenosis, dental caries. 1.Severe or infantile malignant form FIG 6 XRAY SKULL LATERAL VIEW OF THE PATIENT Autosomal recessive form presenting at birth or first year of Showing THICKENED BASE OF SKULL life. DIFFERENTIAL DIAGNOSIS Dense scelerotic bones,fractures,neurological 1.Chronic thalassemia symptoms,bone marrow failure,infections and early death 2.Rickets are the hall mark of this type. 3.Chronic renal failure 2.Intermediate form 4.Leukemia May be dominant or recessive inheritance. Mild 5.Osteopetrosis scelerosis,mental retardation and renal tubular acidosis(CA DIAGNOSIS II),short stature,fractures might be the presentation. Finally , the child was diagnosed to have “Intermediate Type of These patients may be candidates for hematopoietic stem Osteopetrosis “ in the background of the following features such as cell transplantation,but pros and cons should be evaluated haematopoietic failure, skeletal dysplasia,lower motor neuron type on individual basis and discussed with an expert. of facial palsy and characteristic radiological findings. 3. Mild/late onset form TREATMENT It is a benign adult form with a dominant pattern of Child was treated with packed red blood cell transfusion and vitamin inheritance. -D & calcium supplements.Child is on regular follow up in the Autosomal dominant type 1 – very mild,with diffuse hematology clinic with regular blood component therapy once in a scelerosis and without any biochemical or haematological month. changes. DISCUSSION ON OSTEOPETROSIS: Autosomal dominant type 2 – heterogenous course ranging In Greek osteo means “ bone “ and petros means “ stone from asymptomatic to severe form. “.Osteoclasts are specialized cells crucial for bone remodelling Radiological findings which degrade bone mineral and organic bone matrix. 1. - The hall mark of osteopetrosis is the Osteopetrosis occurs due to decreased or defective osteoclasts increased radio opacity of the bones.Loss of resulting in defective . Pathologically osteopetrosis corticomedullary differentiation occurs because the is classified into 1. Osteoclast rich type and 2. Osteoclast poor intramedullary canal is filled with endochondral new bone. type . Clinically osteopetrosis is divided as follows according to 2.Bone in bone appearance- Endo bones are ESID(European Society for Immuno Deficiencies) and the EBMT miniaturized,radio dense tissues that resemble tiny (European group for Blood and Marrow Transplantation) working bones inside the cortices of the tubular bones. They are party on inborn errors. pathognomonic of osteopetrosis. Endobones are most noticeable in early childhood and are best seen in the tarsals,tibia,fibula,,,vertebrae and pelvis. 3.Horizontal striations – Seen in long bones. They consist of alternating zones of sclerosis and relative lucency ,which correlate with the activity of the disease. Vertical lucencies may be seen that represent vascular coloumns. 4.Spine shows Rugger – jersey appearance , Picture frame vertebra , Sandwitch vertebra. In early childhood the vertebral bodies are uniformly radiodense. The vertebrae appear like sandwiches,with osteosclerosis adjacent to the end-plates but relative radiolucency in the middle of the vertebral body.

An Initiative of The Tamil Nadu Dr. M.G.R. Medical University University Journal of Medicine and Medical Specialities

5.Erlen Meyer flask deformity - Bone modelling defects at the metaphyses of long bones create a funnel like appearance. Though the bone mineral content is increased,the bones are brittle by which pathological fractures of long bones may occur even with trivial trauma. Investigations Complete blood count with peripheral blood smear sturdy, Serum calcium,phosphorus, Serum lactate dehydrogenase, Renal function tests, Liver function tests , Xray ( extremities, head , ),USG ( head and abdomen ) ,MRI brain , Bone marrow biopsy , Molecular genetics, HLA typing of the family and patient , Immunoglobulin assay , Lymphocyte subset assay . Treatment Vitamin D and calcium supplementation , Gamma interferon therapy , Blood transfusion, Haematopoietic stem cell transplantation . Indications for stem cell transplantation include haematological failure, imminent loss of vision . Contraindications for stem cell transplantation are neuronopathic form ,extrinsic osteoclast defect with RANKL mutation. Complications Due to the disease : Pathological fractures, , , Bone marrow suppression , Haematological failure Recurrent infection , blindness and deafness. Due to stem cell transplantation : Venoocclusive disease, Pulmonary hypertension , Hypercalcemia, Secondary graft failure , Dwarfism , , Intracranial hypertension,Autism , . Prenatal diagnosis : 1. In families with severe autoaomal recessive osteopetrosis and unknown mutations prenatal diagnosis may be possible at 25th week of gestational age by using fetal radiography & ultrasonography. 2. Preimplantation , prenatal diagnosis is possible in families ,in whom the genetic mutation has been identified already. Characteristic features of the case report A 4 1/2 year old male child presented with 1 Severe anemia and Hepatospleenomegaly 2. Short stature 3.LMN type of facial palsy 4.Cranio facial malformation 5 Hypo calcemia and fractured left arm. X – ray revealed the classical "bone within bone appearance” and osteosclerosis by which we arrived at the diagnosis of osteopetrosis and based on age of onset and severity classified it as intermediate form of osteopetrosis. Conclusion 1. Any child presenting with anemia,clinical evidence of skeletal dysplasia and features of cranial neve entrapment like LMN type of facial palsy can be diagnosed as having OSTEOPETROSIS with help of characteristic radiological findings such as bone in bone appearance(endo bone formation),pathological fractures,generalised increased bone density and picture frame vertebrae. 2. Though osteopetrosis is a rare genetic disorder ,the diagnosis is made possible with clinico radiological evaluation itself without any need of genetic analysis. But genetic analysis may be useful to decide about recent treatment options like stem cell transplantation because stem cell transplantation will not be effective for certain genetic mutations like RANKL mutation. References 1.Osteopetrosis Consensus Guidelines For Diagnosis,Therapy And Follow Up – ESID And EBMT Wp Inborn Errors. 2.Zornitza stark and Ravi savrirayan;Osteopetrosis ;Orphanet Journal Of Rare Diseases 2009,4;5 3.Dr.Callum J Wilson;Autosomal Recessive Osteopetrosis; Or- phaned Encyclopedia:March 2003 4.Jakub Tolar et al; Osteopetrosis;The New England Journal Of Medicine ;December 2004;351,27. 5.Online Mendelian Inheritance in Man-Omm. An Initiative of The Tamil Nadu Dr. M.G.R. Medical University University Journal of Medicine and Medical Specialities