Endocrine Manifestations and New Developments in Mitochondrial Disease

Abstract

Mitochondrial diseases are a group of common inherited diseases causing disruption of oxidative phosphorylation. Some patients with mitochondrial disease have endocrine manifestations, with diabetes being predominant but also include hypogonadism, hypoadrenalism and hypoparathyroidism. There have been major developments in mitochondrial disease over the last decade that have major implications for all patients. The collection of large cohorts of patients has better defined the phenotype of mitochondrial diseases and the majority of patients with endocrine abnormalities have involvement of several other systems. This means that patients with mitochondrial disease and endocrine manifestations need specialist follow up because some of the other manifestations, such as stroke-like episodes and cardiomyopathy, are potentially life threatening. Also, the development and follow up of large cohorts of patients means that there are clinical guidelines for the management of patients with mitochondrial disease. There is also considerable research activity to identify novel therapies for the treatment of mitochondrial disease. The revolution in genetics, with the introduction of next generation sequencing, has made genetic testing more available and establishing a precise genetic diagnosis is important since it will affect the risk for involvement for different organ systems. Establishing a genetic diagnosis is also crucial since there are important reproductive options have been developed which will prevent the transmission of mitochondrial disease due to mitochondrial DNA variants to the next generation.

Cornstarch protocol for nocturnal hypoglycemia in adult patient with mitochondrial disorder

“…Certain mtDNA depletion syndromes may present with hepatocerebral syndrome causing hypoglycemia with hepatic and neurologic abnormalities, re ected by abnormal liver transaminases and coagulation studies [3]. Growth hormone de ciencies have mostly been reported as a factor in the development of short stature in patients with MTDs, as seen in our patient [8].…”

“…The endocrine system is commonly affected, predominantly manifesting as diabetes mellitus as well as hypogonadism, hypoadrenalism, and hypoparathyroidism [3]. A 2019 study found that on chart review, non-diabetic patients with MTD had signi cantly increased rates of hypoglycemic episodes compared to the general population [4], although this complication is not well studied.…”

“…Patients typically require liver transplantation and frequently have progressive neurological involvement such as generalized hypotonia, neurodevelopmental delay, and muscle weakness, and sometimes neuropathy and intractable epilepsy [3].…”

A cause of encephalopathy not to be missed

“…This man’s height is 1.75 m (body mass index 26.1 kg/m 2 ), which would be unusual for people with classical type 2 diabetes. Interestingly, people with m.3243A>G-associated maternally inherited diabetes and deafness are invariably lean at presentation 3…”

Blood pressure regulation is multifactorial in mitochondrial disorders

“…Fifth, hormone levels strongly influence BP values. As MIDs frequently manifest with endocrine involvement [4], it is crucial to know how many of the included patients had endocrine disturbances.…”