“Revolutionary” News From Medicine: 1 in 200 People Carry Mitochondrial Disease Mutation
Both Mitochondrial “disease” and “dysfunction” appear to be more common than previously thought — implications for autism, other disorders are “earth shattering.”
By David Kirby on Huffington Post.
In February, when the US government conceded that vaccines had caused an autism-inducing reaction in little Hannah Poling, most experts declared that her underlying condition, a mitochondrial disorder, was exceedingly rare – so rare, in fact, that it had no bearing on other autism cases.
But today, the United Mitochondrial Disease Foundation announced a “landmark research finding” showing that at least one in 200 healthy humans “harbors a pathogenic mitochondrial mutation that potentially causes disease.” The finding was published in the current issue of the American Journal of Human Genetics. “This is earth shattering news,” UMDF Executive Director and CEO Charles A. Mohan, Jr. told me this evening. “Some of my colleagues are calling it ‘revolutionary.’ We have shown that mitochondrial disease is not rare.”
Mitochondria are the little powerhouses found within most cells and are responsible for producing most of the body’s energy. Mitochondria are key for proper neurotransmission and, for obvious reasons, are highly concentrated in cells of the brain and central nervous system.
Up until now, estimates of mitochondrial disease rates have held steady at about 1-in-4000 people. But this study shows that 20 times that number have genetic mutations that could cause mitochondrial disease.
“What this says to me is that many more than 1-in-4,000 people have mitochondrial disease,” Mohan said. “And it tells me that 1-in-200 could develop some type of mitochondria-related disease over the course of their lifetime, depending in part on environmental triggers.”
Mitochondrial disorders are found at “the core of many well known diseases and chronic illnesses, such as Alzheimer’s disease, Parkinson’s disease and autism spectrum disorders,” a statement from the UMDF said today.
Humans have two types of DNA: nuclear, and mitochondrial. The study looked at 10 mutations in mitochondrial DNA that are known to cause disease, and identified them in the cord blood of 1 in 200 newborn children.
The study looked exclusively at classic mitochondrial “disease.” In the classic form, inherited mutations of mitochondrial DNA are passed down through the mother, causing a wide variety of pathologies, including seizures, digestive problems, paralysis, blindness, heart disease, neurodevelopmental disorders and other problems.
The classic form is often quite severe, and sometimes fatal. But it is not rare.
Which brings us to Hannah Poling: She does not have “classic,” maternally inherited mitochondrial disease.
Hannah does share the same single-point mutation in mitochondrial DNA as her mother, Terry. But this mutation is apparently benign (Terry Poling is just fine), is not described in the medical literature, and is not associated with any pathology at all.
Instead, Hannah seems to have had a much milder, even asymptomatic form of mitochondrial “dysfunction” – one that led to reduced cellular energy, but no obvious signs of severe mitochondrial “disease.”
In April, I reported that researchers in Baltimore were studying 30 children at one autism clinic who all had nearly identical markers for mild mitochondrial dysfunction. One of them was Hannah Poling.
All 30 children were developing normally until they encountered some type of immunological stress and began showing signs of regressive autism soon afterwards.
In 28 cases, the doctors said, typical childhood fevers caused the stress, while in the other two cases, including Hannah, vaccines appeared to be the exacerbating factor.
The doctors – who spoke on a CDC conference call that included executives from the health insurance industry — reported that mitochondrial dysfunction was found in autism “in numbers that make it not a rare occurrence.”
Some estimates currently put the rate of mitochondrial dysfunction in ASD at 7-20%, while rates among regressive autism cases could climb much higher than that.
This milder form of mitochondrial disorder, the doctors said, was probably caused by a mutation found in nuclear (as opposed to mitochondrial) DNA, and inherited through the father — rather than through the mother, as in classic mitochondrial disease.
Shockingly, the nuclear DNA mutations that bring risk of dysfunction could be as common as 1-in-400 to 1-in-50 people – though no one knows how many people have developed actual mitochondrial disorders because of it.
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#2: 678 J Med Assoc Thai Vol. 88 No.5 2005 Correspondence to : Puavilai S, Division of Dermatology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Rama VI Rd, Bangkok 10400, Thailand. Phone:
0-22201-1141, 0-2201-1686, Fax: 0-2201-1211
Herpes Zoster, Clinical Course and Associated Diseases: A 5-Year Retrospective Study at Ramathibodi Hospital Sutasinee Tunsuriyawong, MD*, Siripen Puavilai, MD*
* Department of Medicine, Ramathibodi Hospital, Mahidol University
Objective: Herpes zoster was more frequently found in immunocompromised hosts and elderly persons than in general population. The aim of this study is to find out the distributions of skin lesions, treatments, complications of herpes zoster and associated diseases that occur in concomitant with or after herpes zoster infections.
Material and Method: The medical records of the patients diagnosed as herpes zoster between January 1995- December 2000 were reviewed. Only the patients who were followed up regularly at Ramathibodi hospital for at least 3 years after the first diagnosis of herpes zoster were enrolled into the study. Demographic data, distribution of skin lesions, treatments, complications of herpes zoster and associated diseases were recorded.
Results: Three hundred and ninety-nine cases were enrolled in the study. Three hundred and ninety-eight patients (99.7%) had one dermatomal involvement. Sixty-seven patients (16.8%) had postherpetic neuralgia.
Fifty-six patients had associated HIV infection. In 3 years followed up, 17 patients developed HIV infection, 3 patients developed acute leukemia, 2 patients developed mycosis fungoides.
J Med Assoc Thai 2005; 88(5): 678-81
Full text. e-Journal: http://www.medassocthai.org/journal
Herpes zoster represents reactivation of the latent varicella-zoster virus in the sensory ganglia. The cutaneous eruptions consist of painful vesicles with or without itchiness which tend to follow a unilateral dermatomal distribution. Prodromal pain may often precede the development of visible lesions. The entire course is usually 2-3 weeks in duration. The two most commonly involved areas for herpes zoster are thoracolumbar (T3-L2) and facial dermatomes (first branch of the trigeminal nerve)(1). Anyone who has had varicella may develop herpes zoster. However, it usually develops in persons older than 50 years, and the incidence increases with advancing age. Herpes zoster is more frequently found in immunocompromised individuals and also as an early manifestation of HIV infection. Approximately 10-20% of patients with herpes zoster will experience a recurrence; such recurrence involves the same dermatome in about 50% of these patients(2).
Disseminated herpes zoster is defined as the presence of more than 20 vesicles outside the primary and adjacent dermatomes. Disseminated herpes zoster is uncommon in immunocompetent patients, but 25-50% of immunocompromised patients may develop this complication(3).
Postherpetic neuralgia is the most common complication of herpes zoster. It is defined as the presence of pain after skin lesions have healed, or pain lasting more than 4-6 weeks after disappearance of cutaneous lesions(4). The pain is often severe and debilitating. It occurs in 8-15% of patients(4), but the incidence increases dramatically with age.
The aim of this study was to find out the clinical course of herpes zoster and the associated diseases that occur in concomitant with or after herpes zoster infection.
Material and Method
Using the Ramathibodi Hospital computerized medical record database, the authors compiled a list of patients diagnosed with herpes zoster who attended J Med Assoc Thai Vol. 88 No.5 2005 679 the Department of Medicine, Ramathibodi Hospital over a 5-year period between January 1995 – December 2000. Only the patients with at least 3 years of followup after the first diagnosis of herpes zoster were enrolled into the study. All available charts were reviewed.
The following data were recorded:
1. Demographic data (sex and age)
2. Underlying diseases at the onset of herpes zoster 3. Clinical manifestations (skin lesions, distribution of skin lesions) 4. Complication (postherpetic neuralgia) 5. Associated diseases that occurred within 3 years of the onset of herpes zoster
There were 612 patients diagnosed as herpes zoster from January 1995 to December 2000. Only 399 records can be enrolled into the study. There were 297 males (74%) and 102 females (26%). Age range from 22-81 years (mean + SD = 59 + 7 years).
Three hundred and eighty-two patients (95.7%) experienced one episode of herpes zoster and only 17 (4.3%) patients had a recurrent episode. The duration from the first episode to the second episode ranged from 4 months – 5 years (mean + SD = 2 + 0.4 years).
Three hundred and ninety-eight patients (99.7%) had one dermatomal involvement and only one patient had disseminated herpes zoster. This patient had associated HIV infection.
Information regarding distribution of skin lesions was available in only 178 patients. The most common anatomic segment was the trunk (114 patients: 64%) followed by the face (64 patients; 36%) (Table1). Among this group, 25 patients (39%) had ophthalmic involvement.
Postherpetic neuralgia was found in 67 patients (16.7%). There were 59 patients aged > 60 years and 8 patients aged between 40-60 years. The duration of postherpetic neuralgia ranged from 1-9 months (mean + SD = 2 + 0.3 months). Thirty-eight patients (56.7%) were treated with tricyclic antidepressants (amitriptyline). Twelve patients (17.9%) were treated with gabapentin. Seven patients (10.4%) were treated with tramadol. The recovery time ranged from 2 weeks to 4 months (mean + SD = 3.4 + 2 weeks) after treatment, There was no difference in recovery times between each treatment.
The underlying diseases of the patients were as follows: HIV in 56 patients (14%) dyslipidemia in 22 patients (5.5%) hypertension in 16 patients (4%), diabetes mellitus in 10 patients (2.5%) and breast cancer in 3 patients (0.75%) (Table2).
After a 3-year follow-up, HIV infection was detected in 17 patients (4.2%), other diseases were erythema nodosum in 5 patients, acute leukemia in 3 patients, mycosis fungoides in 2 patients, pyogenic granuloma at the same area of herpetic infection in 1 patient, squamous cell carcinoma on the upper lip in 1 patient and molluscum contagiosum at the lesion in 1 patient (Table 3).
Table 1. Distribution of skin lesions
Anatomic segment No. of patients % of patients Trunk 114 64 Face 64 36 Table 2. Underlying diseases at the onset of herpes zoster Underlying disease No. of patients % of patients HIV 56 14.0 Dyslipidemia 22 5.5 Hypertension 16 4.0 Diabetes mellitus 10 2.5 Breast cancer 3 0.75 Table 3. Associated diseases detected during 3 years after onset of herpes zoster Diseases No. of patients % of patients Duration detected after onset of herpes zoster (months) HIV 17 4.2 1-7 Erythema nodosum 5 1.2 4-24 Acute leukemia 3 0.75 2-7 Mycosis fungoides 2 0.5 8-24 Pyogenic granuloma 1 0.25 6 Squamous cell carcinoma at upper lip 1 0.25 24 Molluscum contagiosum 1 0.25 unknown 680 J Med Assoc Thai Vol. 88 No.5 2005
Herpes zoster is caused by reactivation of latent varicella-zoster virus (VZV), a double stranded DNA virus in the Alphaherpesvirus family, which is also the causative virus of primary varicella(4). After initial infection with clinical manifestation of chickenpox, VZV remains latent in dorsal root or cranial nerve ganglion for life. Declining virus-specific cellmediated immune response, which occurs naturally as a result of aging or by immunosuppressive illness or immunosuppressive drugs increased the risk of herpes zoster(5).
In the present study, which retrospectively gathered information on 399 patients diagnosed as herpes zoster, affirms previously reported information regarding sex, age and distribution of the skin lesions(1,2,5), but extends and adds to those observations.
Specifically, the present study is the first study to find out the associated diseases with herpes zoster at the time of onset of herpes zoster and three years afterwards.
Eye involvement was found in 39% of the patients who had facial lesions so ophthalmologic consultation is recommended in this group.
Postherpetic neuralgia is the most painful manifestation in these patients. Both the incidence and duration of postherpetic neuralgia are directly correlated with the age of the patients. The reported incidence of postherpetic neuralgia range from 8 to 70% and increased with advancing age. In patients over 50 years, 20% of patients continued to report pain six months after the onset of the rash despite treatment with valacyclovia or famcyclovia(6). In the present study, postherpetic neuralgia occurred in 16.8% of the patients, most of the patients were more than 60 years old. This is in agreement with other studies that postherpetic neuralgia mostly occurred in old age(6,7).
Treatment of postherpetic neuralgia is difficult. Clinical trials have shown that opioids, tricyclic antidepressant and gabapentin reduced the severity and duration of postherpetic neuralgia, either as a single agent or in combination(6,7). In the present study the authors found tricyclic antidepressants were most commonly used (56.7%). But there was no difference in terms of recovery among all pain-relieving medications.
In the present study, the authors found that 56 patients (14%) had HIV infection at the time of diagnosis of herpes zoster. Seventeen patients (4.2%) were detected to have HIV during the follow-up periods. There were three possibilities for the detection of HIV in these 17 patients: 1) some of them might really be new cases 2) some might be in the window period 3) the physician did not request for a laboratory investigation for HIV at the time of onset of herpes zoster. Unfortunately, the information in the medical record was inadequate to clarify these possibilities.
From the previous studies herpes zoster affected about 8-11% of patients with AIDS(4,8). HIV patients commonly have cell counts between 200-400 cells/mm3 when they had the first episode of herpes zoster(9-13).
Unfortunatedly, the authors did not have cell count records of the presented patients. The high percentage of HIV patients in the present study points out the importance of HIV screening in all herpes zoster patients, especially those who in the recognized risk group for HIV infection.
Herpes zoster has been reported to be associated with malignancy, especially in elderly persons. The patients who had Hodgkin’s disease, non-Hodgkin’s lymphomas, and leukemia possess a high risk for herpes zoster(14,15). The patients with solid tumors have a lesser risk for herpes zoster, but treated patients with lung, breast or gynecologic cancers of any age are more likely to have herpes zoster than patients with other solid tumors(15). In the present study, herpes zoster occurred in 3 patients who had underlying breast cancer. After a 3 year follow-up of these patients with herpes zoster, three patients developed acute leukemia, two patients developed mycosis fungoides, and one patient developed squamous cell carcinoma, although herpes zoster is not a risk factor for cancer(16,17).
Long term follow up for at least 2 years should be considered in patients with herpes zoster, especially in the older age group.
In conclusion, the incidence of herpes zoster is increasing nowadays. Old age and immunocompromised host are important predisposing factors and herpes zoster is a frequent early manifestation of HIV infection.
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