Mitochondrial disorder caused Charles Darwin's cyclic vomiting syndrome

Abstract

BackgroundCharles Darwin (CD), “father of modern biology,” suffered from multisystem illness from early adulthood. The most disabling manifestation was cyclic vomiting syndrome (CVS). This study aims at finding the possible cause of CVS in CD.MethodsA literature search using the PubMed database was carried out, and CD’s complaints, as reported in his personal writings and those of his relatives, friends, colleagues, biographers, were compared with various manifestations of mitochondrial disorders (MIDs), known to cause CVS, described in the literature.ResultsOrgan tissues involved in CD’s disease were brain, nerves, muscles, vestibular apparatus, heart, gut, and skin. Cerebral manifestations included episodic headache, visual disturbance, episodic memory loss, periodic paralysis, hysterical crying, panic attacks, and episodes of depression. Manifestations of polyneuropathy included numbness, paresthesias, increased sweating, temperature sensitivity, and arterial hypotension. Muscular manifestations included periods of exhaustion, easy fatigability, myalgia, and muscle twitching. Cardiac manifestations included episodes of palpitations and chest pain. Gastrointestinal manifestations were CVS, dental problems, abnormal seasickness, eructation, belching, and flatulence. Dermatological manifestations included painful lips, dermatitis, eczema, and facial edema. Treatments with beneficial effects to his complaints were rest, relaxation, heat, and hydrotherapy.ConclusionCVS in CD was most likely due to a multisystem, nonsyndromic MID. This diagnosis is based upon the multisystem nature of his disease, the fact that CVS is most frequently the manifestation of a MID, the family history, the variable phenotypic expression between affected family members, the fact that symptoms were triggered by stress, and that only few symptoms could not be explained by a MID.

Darwin diagnosed?

“…But his full symptoms do not fit Ménière's disease itself (Gordon, , b). Other conditions proposed include various gut ailments, such as cyclic vomiting syndrome, and Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke‐like episodes (MELAS), involving an inherited mitochondrial mutation (Hayman, ; Finsterer & Hayman, ), irritable bowel syndrome (IBS) (Shanahan, ), and Crohn's disease (Orrego & Quintana, ). His regular bouts of vomiting certainly fit the diagnosis of cyclic vomiting syndrome (Hayman, , b, ), which is associated with nausea, abdominal pain and dyspepsia.…”

“…(); Waud et al . (); Finsterer & Hayman (). Darwin's description of ‘belching’ may have included what we now call ‘flatulence’, which the Victorians often found embarrassing to talk about.…”

“…See (Colp, 1960(Colp, , 1977(Colp, , 1983(Colp, , 2000(Colp, , 2006 M eni ere's spectrum disorder (Gordon, 2009a, b) Systemic lactose intolerance (Campbell, 2003;Campbell, & Matthews 2005a, b;Campbell et al, 2005b;Dixon & Radick, 2009) MELAS from mitochondrial gene mutation (Hayman, 2013b;Finsterer & Hayman, 2014) Gout (Darwin, 1876;Colp, 2006) Hyperinsulinism (Lichfield, 2015) Malaria (Hayman, 2009a(Hayman, , 2013) Systemic lupus erythematosis (Hayman, 2009a(Hayman, , 2013 Pyroluria (Hayman, 2009a(Hayman, , 2013) Irritable bowel syndrome (Shanahan, 2012) Crohn's disease (Orrego & Quintana, 2007) Fearing he had had a heart attack, Darwin told no one, lest he was not allowed on his voyage of a lifetime. He only admitted to this in his autobiography (Darwin, 1876(Darwin, , 1902.…”

Diagnoses for Charles Darwin’s Illness: A Wealth of Inaccurate Differential Diagnoses

“…Jared Goldstein summed this up succinctly: “ Take your pick, there’s something for everybody: hypochondriasis, refractive error, depression, arsenic poisoning, Oedipal complex, pigeon allergy, familial psychosis, chronic brucellosis, chronic anxiety, Chagas’ disease, and more ” [ 2 ]. The diagnosis that is favored here, that of a mitochondrial disorder due to a maternally inherited pathological mitochondrial DNA (mtDNA) mutation, should be seen against this background and subject to similar critical appraisal [ 3 ].…”

Charles Darwin’s Mitochondrial Disorder: Possible Neuroendocrine Involvement

“…The diagnosis favoured here is that of adult-onset mitochondrial disorder due to a maternally inherited pathological mitochondrial DNA (mtDNA) mutation, particularly MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) syndrome [ 5 ]. This diagnosis accounts for Darwin’s primary symptoms (Table 1 ) including his cyclic vomiting [ 14 ]. Family study shows that this mutation was inherited from his Wedgwood ancestors through his mother Susannah (1765-1817), shared with her siblings Tom Wedgwood (1771-1805) and Mary Ann (1778-1786) [ 15 ].…”