Med Bull Sisli Etfal Hosp. 2022; 56(1): 161-165 | DOI: 10.14744/SEMB.2021.88964

A Neonatal Case of Infantile Malignant Osteopetrosis Presenting with Thrombocytopenia and Hypotonicity: A Novel Mutation in Chloride Voltage-Gated Channel 7 Gene

Isik Odaman Al¹, Yesim Oymak¹, Filiz Hazan², Semra Gursoy³, Tulay Ozturk⁴, Ozlem Bag⁵, Salih Gozmen¹, Nurgul Karakaya¹, Tuba Hilkay Karapinar^1
1Department of Pediatric Hematology and Oncology, Dr. Behçet Uz Child Disease and Pediatric Surgery Training and Research Hospital, Izmir, Turkey
²Department of Medical Genetics, Dr. Behçet Uz Child Disease and Pediatric Surgery Training and Research Hospital, Izmir, Turkey
³Department of Pediatric Medical Genetics, Dr. Behçet Uz Child Disease and Pediatric Surgery Training and Research Hospital, Izmir, Turkey
⁴Department of Pediatric Radiology, Dr. Behçet Uz Child Disease and Pediatric Surgery Training and Research Hospital, Izmir, Turkey
⁵Department of Pediatrics, Dr. Behçet Uz Child Disease and Pediatric Surgery Training and Research Hospital, Izmir, Turkey

Autosomal recessive osteopetrosis is also known as infantile malignant osteopetrosis (IMO). The clinical course is often serious and if left untreated, it is fatal in the 1st year of life. Diagnosis is challenging and often delayed or misdiagnosed. Herein, we present an infant girl who was diagnosed with IMO during evaluations for her hypotonicity and thrombocytopenia. A novel mutation of the chloride voltage-gated channel 7 (CLCN7) gene was also reported. A 10-day-old female patient was referred to our hospital for evaluation of hypotonicity. Her physical examination was normal, other than hypotonicity. Laboratory analysis revealed thrombocytopenia and hypocalcemia. In the progress, while she was followed in outpatient clinic, hepatosplenomegaly was detected at the age of 3 months. IMO was suspected with the findings of hepatosplenomegaly, cytopenia, hypocalcemia, difficulty of obtaining bone marrow, peripheral smear findings, and hearing loss. The X-ray of the bones was consistent with IMO. A novel pathogenic homozygous c.1504>T (p.Arg502Trp) mutation in CLCN7 gene was revealed. IMO is a rare disorder and it is important to differentiate this entity for better clinical outcome. The presence of neurological and hematological findings, organomegaly, hearing loss, and vision disorders must attract attention to IMO.

Keywords: Chloride voltage-gated channel 7 gene, Leukoerythroblastosis, Novel mutation, Osteopetrosis, Thrombocytopenia

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Yenidoðan Döneminde Hipotonisite ve Trombositopeni ile Baþvuran Bir Ýnfantil Malign Osteopetrozis Olgusu: CLCN Geninde Yeni Bir Mutasyon Bildirimi

Isik Odaman Al¹, Yesim Oymak¹, Filiz Hazan², Semra Gursoy³, Tulay Ozturk⁴, Ozlem Bag⁵, Salih Gozmen¹, Nurgul Karakaya¹, Tuba Hilkay Karapinar^1
1Dr. Behçet Uz Çocuk Hastalýklarý ve Çocuk Cerrahisi Eðitim ve Araþtýrma Hastanesi, Pediatrik Hematoloji ve Onkoloji Bölümü, Ýzmir
²Dr. Behçet Uz Çocuk Hastalýklarý ve Çocuk Cerrahisi Eðitim ve Araþtýrma Hastanesi, Týbbi Genetik Bölümü, Ýzmir
³Dr. Behçet Uz Çocuk Hastalýklarý ve Çocuk Cerrahisi Eðitim ve Araþtýrma Hastanesi, Pediatrik Týbbi Genetik Bölümü, Ýzmir
⁴Dr. Behçet Uz Çocuk Hastalýklarý ve Çocuk Cerrahisi Eðitim ve Araþtýrma Hastanesi, Çocuk Radyolojisi Bölümü, Ýzmir
⁵Dr. Behçet Uz Çocuk Hastalýklarý ve Çocuk Cerrahisi Eðitim ve Araþtýrma Hastanesi, Çocuk Saðlýðý ve Hastalýklarý Bölümü, Ýzmir

Otozomal resesif osteopetrozis, infantil malign osteopetrozis (IMO) olarak da bilinir. Genellikle aðýr bir klinik gidiþ gösterir ve tedavi edilmezse hayatýn ilk yýllarýnda ölümle sonuçlanýr. Taný koymak zordur ve genellikle yanlýþ taný konulur ya da taný konulmasý gecikir. Burada hipotonisite ve trombositopeni nedeni ile tetkik edilirken IMO tanýsý konulan ve CLCN7 geninde yeni bir mutasyon saptanan olguyu sunmak istiyoruz. On günlük kýz hasta hipotonisite nedeni ile tetkik amaçlý hastanemize gönderildi. Fizik muayenesi hipotonisite dýþýnda normaldi. Tetkiklerinde trombositopeni ve hipokalsemi saptandý. Klinik izleminde 3 aylýkken hepatosplenomegalisi fark edildi. Direk kemik grafileri IMO ile uyumluydu. Moleküler incelemede CLCN7 geninde yeni bir homozigot c.1504>T (p.Arg502Trp) mutasyonu saptandý. IMO nadir görülen bir hastalýktýr ve daha iyi klinik sonuçlar elde etmek için hastalýðýn farkýna varýp erken taný konulmasý önemlidir. Nörolojik ve hematolojik bulgular, organomegali, iþitme kaybý ve görme bozukluklarý IMO’yu düþündürmelidir. (SETB-2021-03-093)

Anahtar Kelimeler: osteopetrosis, CLCN7 geni; trombositopeni; lökoeritroblastozis; yeni mutasyon

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