Congenital cataract as the first symptom of a neuromuscular disease caused by a novel single large-scale mitochondrial DNA deletion

Abstract

The male proband reported here was born with appropriate anthropometric parameters at term as the second child of healthy nonconsanguineous parents. His only clinical symptom was bilateral congenital cataracts with strabismus at birth, and both lenses were removed surgically at the age of 8 months. The perinatal and infantile period thereafter was clinically uneventful and his psychomotor development appeared almost normal. At the age of 6 years he was hospitalized for slight muscle weakness, minor ptosis, nystagmus and decreased physical activity. Soon after, his general condition worsened, gait ataxia presented, dysphagia and difficulty of speech followed by rapidly progressive generalized ataxia, and myopathy developed. Typical progressive gray matter degeneration with focal necrosis in the basal ganglia characteristic of the Leigh type of neuropathology could be detected by cranial MRI, the muscle histology showed ragged-red fibers. At the age of 7.5 years, unexpected left side hemiparesis with speech disability resembling that seen in MELAS syndrome developed, from which he recovered within 1.5 days. The mtDNA of the patient showed single 6.7 kb large-scale deletion harboring between 7817 and 14 536 bp. This case represents the first report of a verified mtDNA mutation associated with congenital cataracts as the first clinical sign of a later developing progressive neuromuscular disease presented with a combination of Leigh neuropathology, ragged-red fiber histopathology and stroke-like attack.

Gastrointestinal manifestations of mitochondrial disorders: a systematic review

“…In patients carrying POLG1 mutations, dysphagia may be accompanied by CPEO, seizures, neuropathy, ataxia, hepatopathy, or migraine [Woodbridge et al 2013]. In a 6-year-old boy with a single mtDNA deletion manifesting as stroke-like episodes and Leigh-like neuropathology, dysphagia was one among numerous other phenotypic features [Bene et al 2003].…”

Early-Onset Cataracts, Spastic Paraparesis, and Ataxia Caused by a Novel Mitochondrial tRNAGlu(MT-TE) Gene Mutation Causing Severe Complex I Deficiency: A Clinical, Molecular, and Neuropathologic Study

“…Cataracts are a rarely described feature in mtDNA disease (24). Here, our patient had early-onset bilateral cataracts, which may have resulted in delayed diagnosis of pigmentary retinopathy that is frequently described in mtDNA diseases, such as Kearns-Sayre syndrome (25).…”

Maternally inherited deafness and unusual phenotypic manifestations associated with A3243G mitochondrial DNA mutation

“…8,31,35 Consequently, the disorders inherited through the mtDNA can associate with an extremely variable clinical phenotype. 1,22 These may remain undiagnosed in case they present with isolated, single symptoms, failing to show the full-blown clinical picture. Among the disorders caused by alterations of the mitochondrial genome, special attention…”