The m.9143T>C Variant: Recurrent Infections and Immunodeficiency as an Extension of the Phenotypic Spectrum in <i>MT-ATP6</i> Mutations?

• Main Authors: Diana Lehmann Urban, Leila Motlagh Scholle, Matias Wagner, Albert C. Ludolph, Angela Rosenbohm
• Format: Article
• Language: English
• Published: MDPI AG 2020-06-01
• Series: Diseases
• Subjects: <i>MT-ATP6</i>; mitochondrial disease; immune deficiency; phenotypic spectrum
• Online Access: https://www.mdpi.com/2079-9721/8/2/19

Pathogenic variants in the <i>MT-ATP6</i> are a well-known cause for maternally inherited mitochondrial disorders associated with a wide range of clinical phenotypes. Here, we present a 31- year old female with insulin-dependent diabetes mellitus, recurrent lactic acidosis and ketoacidosis recurrent infections with suspected immunodeficiency with T cell lymphopenia and hypogammaglobulinemia as well as proximal tetraparesis with severe muscle and limb pain and rapid physical exhaustion. Muscle biopsy and respiratory chain activities were normal. Single-exome sequencing revealed a variant in the <i>MT-ATP6</i> gene: m.9143T>C. Analysis of further specimen of the index and mother (segregation studies) revealed the highest mutation load in muscle (99% level of mtDNA heteroplasmy) of the index patient. Interestingly, acute metabolic and physical decompensation during recurrent illness was documented to be a common clinical feature in patients with <i>MT-ATP6</i> variants. However, it was not mentioned as a key symptom. Thus, we suggest that the clinical spectrum might be expanded in <i>ATP6</i>-associated diseases.