Endocrine disorders in a patient with a suspicion of a mitochondrial disease, MELAS syndrome – a case report and literature review

Abstract

MELAS syndrome (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) is a genetically determined disease caused by mutations in mitochondrial DNA. We present a girl who was suspected of MELAS syndrome during the diagnostic evaluation of short stature. The patient suffered from symptoms potentially indicating mitochondrial disease, such as muscular weakness, cranial nerve VI palsy, headaches, retinitis pigmentosa, sensory-neural hearing loss, and elevated lactic acid. T2-weighted brain MRI showed hyperintense lesions in the white matter. Muscular biopsy revealed ragged red fibres. Genetic evaluation did not detect the most common mutations in the MT-TL1 gene and MT-ND5 gene. Endocrine tests led to the confirmation of growth hormone deficiency, and so replacement treatment was started. After 1 year of recombinant growth hormone therapy the patient was diagnosed with diabetes. At the age of 14 years the LH-RH test showed prepubertal values. Endocrine disorders may be one of the first manifestations of MELAS syndrome. In differential diagnosis of short stature, less common causes, such as mitochondrial diseases, should be taken into consideration.

MELAS or Leigh syndrome, that’s the question

“…We do not agree with the diagnosis PCB [ 1 ]. According to the Ropper criteria, absence of alternative diagnoses is warranted [ 2 ].…”

“…With interest we read the article by Baszyńska-Wilk et al . about a 12 years old female who was diagnosed with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome upon the clinical presentation, blood tests, and the cerebral magnetic resonance imaging (MRI) [ 1 ]. The diagnosis was neither confirmed by biochemical nor by genetic investigations [ 1 ].…”

“…Missing is the exclusion of an infection with SARS-CoV-2 as the trigger of GBS. There was neither a search for virus RNA in the nasopharynx nor in the cerebro-spinal fluid (CSF) carried out [ 1 ]. From SARS-CoV-2 infections it is well-known that they can be complicated by GBS [ 3 ].…”

Endocrine features of primary mitochondrial diseases

“…Studies are ongoing. Recently, an 11.5 year-old girl with MELAS, short stature, and GH deficiency had improved growth from 4.2 to 6.5 cm/year after initiation of GH [ 51 ▪ ].…”

Combined MITOchondrial-NUCLEAR (MITO-NUCLEAR) Analysis for Mitochondrial Diseases Diagnosis: Validation and Implementation of a One-Step NGS Method

“…MDs appear in childhood and adulthood and are characterized by defects of oxidative phosphorylation (OXPHOS) due to both mitochondrial DNA (mtDNA) and nuclear genome (nDNA) alterations impairing ATP production [14][15][16]. Moreover, estimates suggest that only about 15-20% of respiratory chain deficit (RCD) is due to mtDNA mutations, while the remaining part is caused by nuclear defects [9].…”