# Malignant Infantile Osteopetrosis With Neurological and Hematological Complications: A Case Review

## TL;DR

A rare and severe bone disease in infants, caused by a genetic mutation, leads to life-threatening complications and highlights the need for early diagnosis and treatment.

## Contribution

The case highlights the challenges of diagnosing and managing malignant infantile osteopetrosis with a specific OSTM1 gene mutation.

## Key findings

- A six-week-old infant with OSTM1 gene mutation presented with severe bone and neurological complications.
- The patient's condition worsened despite treatment, and he died before a scheduled stem cell transplant.
- Early genetic diagnosis and multidisciplinary care are crucial for improving outcomes in this disease.

## Abstract

Infantile malignant osteopetrosis is a rare disease characterized by autosomal recessive skeletal dysplasia secondary to defective bone resorption as a consequence of dysfunctional osteoclasts. It manifests in infancy with bone marrow failure, central nervous system disease, and skeletal impairment. Some genetic subtypes may be potentially curable with hematopoietic stem cell transplantation, but the results are overall poor in patients with advanced neurologic involvement or adverse genetic mutations. We describe the case of a six-week-old male infant born to consanguineous parents, who presented with fever, difficulty in breathing, and progressive irritability. On clinical examination, he had coarse facial features, a systolic heart murmur, sacral hair tuft, and dental anomalies. Laboratory workup revealed a severe anemia, thrombocytopenia, and mildly elevated liver enzymes. Despite antimicrobial empiric therapy, the patient's clinical condition worsened, and a radiological examination showed several pathological fractures and increased bone density. Skeletal survey documented generalized bone sclerosis and remodeling, and the case was diagnosed as osteopetrosis. Cerebral magnetic resonance imaging demonstrated a cystic hygroma, and ocular investigation confirmed that both optic nerves were atrophied and visual evoked potentials were absent. Vitamin D deficiency, an elevated parathyroid hormone (PTH), and normal serum calcium were noted on bone and metabolic panels. Whole-exome sequencing revealed malignant infantile osteopetrosis based on a homozygous deletion in the OSTM1 gene. Immediate care of the infant included the administration of blood and platelet transfusions, nutritional supplementation, and orthopedic intervention. Even though the patient was being scheduled for allogenic haematopoietic stem cell transplantation in a foreign country, he died before the procedure could be arranged. This case underscores the diagnostic challenges and extreme clinical severity of malignant infantile osteopetrosis, especially the genetic subtypes that do not respond to definitive therapies. The mutation in the OSTM1 gene results in severe neurological decline and a very poor outcome. An early genetic diagnosis, a multidisciplinary approach, and regional genetic studies are essential to improve prognosis in the affected infants. Allogeneic hematopoietic stem cell transplantation provides the only curative therapy for some subtypes, but the prognosis is dismal in the presence of extensive neuraxial disease. This case also highlights the need for early prevention of symptoms, genetic counseling, and the ongoing search for new therapies.