Language Skills in a Child With Leber Hereditary Optic Neuropathy Following Intrathecal Chemotherapy for Acute Lymphoblastic Leukemia

Abstract

The language skills of a male child with Leber hereditary optic neuropathy (LHON) and coincidentally treated for acute lymphoblastic leukemia (ALL) with intrathecal chemotherapy at the age of 3 years 8 months were comprehensively evaluated twice over a 6-month period approximately 5½ years after diagnosis of ALL. Despite marked chemotherapy-related leukoencephalopathic changes documented on magnetic resonance imaging, the child presented with stable language skills, which were generally average to above-average based on the normative data from a comprehensive language test battery. In light of the coincidental presentation in the child of a diagnosis of LHON, which may lead to serious vision impairment and increased vulnerability to drug neurotoxicity, coupled with a history of central nervous system (CNS)-directed treatment for ALL resulting in progressive white matter pathology, the study highlights the importance of ongoing monitoring of the child's language development throughout his adolescent years.

Mitochondria as Oxidative Signaling Organelles in T-cell Activation: Physiological Role and Pathological Implications

“…Progression of LHON is sporadically accompanied by hematological malignancies, such as leukemia or lymphoma (Lewis et al 2010;Zanssen and Buse 2003). LHON-related mtDNA mutations were also described for the myelodysplastic syndrome (Linnartz et al 2004).…”

A case for the use of chemotherapy in hereditary mitochondrial optic neuropathies: Successful administration of cisplatin/etoposide in a male patient with testicular seminoma and Leber's hereditary optic neuropathy

“…The second case involved use of intrathecal methotrexate for treatment of acute lymphoblastic leukemia in a 3‐year‐old patient. 17 Marked leukoencephalopathic changes were observed on brain magnetic resonance imaging but measured language skills remained stable. No visual impairment or disease conversion as a consequence of therapy had been reported by the authors.…”

“…An in vitro assay performed on the patient's mononuclear peripheral blood cells did not demonstrate altered vulnerability to mafosfamide and hence the authors concluded that the 11778 mutation did not clinically change cellular response to cytotoxic therapy. The second case involved use of intrathecal methotrexate for treatment of acute lymphoblastic leukemia in a 3‐year‐old patient 17 . Marked leukoencephalopathic changes were observed on brain magnetic resonance imaging but measured language skills remained stable.…”

Increased prevalence of malignancy in mitochondrial disorders

“…These include patients with MELAS-syndrome developing biliary cystadenocarcinoma [ 6 ] or renal cell carcinoma [ 7 ], patients with LHON developing acute lymphoblastic leukemia [ 8 ] or malignant lymphoma [9], patients with maternally inherited diabetes and deafness (MIDD) developing cervical carcinoma [ 10 ], patients with Leigh syndrome developing liver hepatoblastoma [ 11 ], patients with depletion syndrome developing hepatocellular carcinoma [ 12 ], or patients with non-syndromic MID developing thyroid carcinoma [ 13 ]. MIDs in which benign tumors have been reported include MERRF syndrome, associated with lipoma [ 14 - 16 ], LHON, associated with pituitary adenoma [ 17 ], CPEO, associated with lipoma [ 18 ], or non-syndromic MIDs due to a SDH mutation, associated with paraganglioma or pheochromocytoma [ 19 ].…”