Whole mitochondrial genome analysis of a family with NARP/MILS caused by m.8993T>C mutation in the MT-ATP6 gene.

Mutations in mitochondrial DNA (mtDNA) encoded nucleotide 8993 can cause NARP syndrome (neuropathy, ataxia, and retinitis pigmentosa) or MILS (maternally inherited Leigh syndrome). The rare T8993C mutation in the MT-ATP6 gene is generally considered to be clinically milder, but there is marked clinical heterogeneity ranging from asymptomatic carriers to fatal infantile Leigh syndrome. Clinical heterogeneity has mostly been attributed to mtDNA heteroplasmy, but environmental, autosomal, tissue-specific factors, nuclear modifier genes, and mtDNA variations may also modulate disease expression. Here, we report the results of whole mitochondrial genome analysis of a family with m.8993T>C mutation in the MT-ATP6 gene and associated with NARP/MILS, and discuss the familial inheritance, effects of variation in combinations and heteroplasmy levels on the clinical findings. The whole mitochondrial genome was sequenced with ~182× average depth of coverage per sample with next-generation sequencing technology. Thus, all heteroplasmic (>%10) and homoplasmic variations were determined (except for 727C insertion) and classified according to the associations with mitochondrial diseases.

Seropositive neuromyelitis optica: a pediatric case report and 6-year follow-up.

BACKGROUND: Neuromyelitis optica is an autoimmune demyelinating disorder of the central nervous system. Although it has some features in common with multiple sclerosis, it has different clinical features, prognosis, and treatment. We describe a boy with seropositive neuromyelitis optica and his 6-year follow-up. PATIENT: A boy aged 5 years 8 months presented with relapsing optic neuritis, short segment transverse myelitis, and brain involvement. He met the diagnostic criteria for multiple sclerosis fulfilling the McDonald 2010 criteria; however, neuromyelitis optica immunoglobulin-G was detected, and the patient was diagnosed with neuromyelitis optica. He had frequent relapses until immunosuppressive treatment with azathioprine and low-dose prednisone was started. After he was asymptomatic for 2.5 years, prednisone was withdrawn, but he had a new attack soon after withdrawal of the steroid. CONCLUSIONS: It is important to differentiate neuromyelitis optica from multiple sclerosis because early immunosuppressive treatment prevents further disability, and longer periods of immunosuppressive treatment should be planned to prevent relapses.

Permanent neonatal diabetes mellitus: same mutation, different glycemic control with sulfonylurea therapy on long-term follow-up.

Permanent neonatal diabetes mellitus (PNDM) is a rare condition presenting before six months of age. Mutations in the genes encoding the ATP-sensitive potassium (KATP) channel are the most common causes. Sulfonylurea (SU) therapy leads to dramatic improvement in diabetes control and quality of life in most patients who carry these mutations. Here, we report the long-term follow-up results of two siblings with PNDM who were treated with insulin until ABCC8 gene mutation was identified, and were successfully transferred to oral SU therapy. After 3.5 years of follow-up on SU, one patient had a very good response, while the other one had a poor response. Bad compliance to diet was thought to be the most probable reason for poor glycemic control in this patient. In conclusion, molecular genetic diagnosis in all patients with PNDM is recommended. Compliance to treatment should be an important aspect of the follow-up of these patients.