Mon - Fri: 8:00AM - 5:00PM
Monday – Friday8:00AM - 5:00PM
Saturday Open for MRI
Sunday Closed
Migraine treatment same day as your first appointment.
or
Visit our Healow Portal
Visit our Healow Portal Call 214-619-1910
CALL 214-619-1910

What is Alpers Disease: Symptoms and Causes

Medically reviewed by Sandeep Dhanyamraju
Medically reviewed by Sandeep Dhanyamraju

Alpers Huttenlocher syndrome is a rare mitochondrial disease. Scientists associate it with mutations in mitochondrial DNA gamma polymerase (POLG). A decrease in mitochondrial DNA replication leads to a reduction in enzyme activity. The disease manifests itself when replication levels become critical. There is variability in the onset and progression of Alpers disease. It happens even in normal child development until the onset of clinical manifestations. A triad of symptoms characterizing the disease include: 

 

  • epileptic seizures; 
  • liver dystrophy;
  • developmental regression. 

 

Epileptic seizures are usually resistant to treatment and often have a status course. Liver dysfunction is one of the disease manifestations. It is inevitable in the terminal stages. 

A timely diagnosis with a prescription for supportive therapy can increase life expectancy. Also, the exclusion of valproic acid drugs from the therapy works well.

 

What is Alper’s Huttenlocher Syndrome?

Alpers-Huttenloher syndrome is a progressive encephalopathy with degenerative changes. They occur in the brain’s gray matter combined with liver cirrhosis. We can also say that it is a sporadic mitochondrial disease. Mutations in mitochondrial DNA gamma polymerase (POLG) cause this disease. Nuclear genes encode it.

It is the only eukaryotic DNA polymerase involved in continuous mitochondrial DNA replication. A decrease in mitochondrial activity is associated with a decrease in DNA replication. The disease manifests itself when the replication level reaches a critical level.

 

Alper’s disease has been extensively studied throughout the 20th century:

  • In 1976, Peter Huttenlocher confirmed the disease’s autosomal recessive type of inheritance. Also, he described liver changes in this syndrome. Several symptoms are characteristic of Alpers-Huttenloher syndrome. A decrease in cytochrome С-oxidase activity in liver mitochondria causes them:

 

  1. Progressive hepatomegaly;
  2. Fatty dystrophy;
  3. Hepatic fibrosis.

 

  • A 1992 article in Bicknes et al. described the catastrophic effects of valproic acid on the liver in children. It was one of the symptoms of Alper’s syndrome. Valproic acid causes apoptosis of liver cells. It leads to fatal toxic hepatitis and rapid death in children. 
  • In 1995, Harding analyzed the medical histories of 32 patients. All suffered from liver failure and brain pathology. He confirmed the normal psychomotor development of the child before the disease. But after it, the child gets regression of development combined with metabolic crises. The crises went by bouts of vomiting and pronounced muscle hypotonia. He also specified that epileptic seizures could be with the above symptoms. Or the disease can debut with epileptic seizures. These seizures are resistant to therapy and often have a status course.
  • In 2004, scientists identified biochemical and enzymatic changes in Alper’s disease The findings clarified the pathophysiology of the clinical phenotype. They confirmed the genetic etiology and the underlying cause of the disease. It is a disorder of DNA gamma polymerase synthesis. Various dominant and recessive mutations of the POLG gene relate to it.

 

Alper’s Syndrome Symptoms

alpers syndrome symptoms

Seizures manifest Alpers disease in half of the cases. We call “Large epileptic paroxysms”:

  • focal seizures;
  • myoclonic forms. It is rhythmic muscle twitches without muscle spasms;
  • generalized tonic-clonic seizures;
  • dementia.

The typical age of onset is 2 to 4 years. Although scientists have described cases of early onset (3 to 4 months) and late-onset (up to 8 years of age). And the second peak is between 17 and 24 years of age. 

Before the appearance of the first clinical symptoms, children have normal psychomotor development. They also have enough intellectual abilities. After the onset of neurological symptoms, there is a sharp decline in before-acquired skills. A bimodal distribution characterizes what we call Alper’s syndrome

In children, the first seizures are often triggered by a fever with an infectious disease.

 

Many neurological disorders can characterize Alper’s disease:

  • Patients have gait instability, movement disorder, and impaired fine motor skills.
  • Sensory polyneuropathy is manifested by impairment of all types of sensitivity, including paresthesias. 
  • As a rule, there are visual disturbances (cortical blindness). Migraines are disturbing, including as part of an explosive aura.

 

The pronounced toxic effects of valproic acid with the development of toxic fatal hepatitis are independent of:

  • a patient;
  • the type of mutation;
  • the stage of the disease.

 

It usually occurs within 2-4 months. Blood tests determine the following Alper’s syndrome symptoms:

  • hypoglycemia;
  • hyperketonemia;
  • decreased synthesis of clotting factors;
  • increased levels of transaminases. This indicates the initial stage of liver failure. 

 

In rare cases, doctors can stop liver failure by canceling the medication. It is the valproic acid that causes the failure. In the terminal stages of the disease, liver dysfunction is inevitable. 

 

What Serious Conditions Can Occur in Alper’s Disease?

Hypoglycemia can be one of the early symptoms of the disease. This is especially true in the first two years of life. Hypoglycemia occurs with decreased mitochondrial electrolyte transport system activity. Also, it happens due to a nuclear DNA mutation. In this case, the doctor can identify what Alper’s Huttenlocher syndrome is:

  • abnormalities in the hemostasis system;
  • a deficiency of vitamin K-dependent clotting factors.

 

Deep vein thrombosis is common in patients with Alpers Huttenlocher syndrome. These are predominantly subclavian or femoral veins. This is due to a lack of synthesis of anticoagulant proteins.

 

Associated Alper’s syndrome symptoms are: 

  • High body temperature;
  • Impaired gait;
  • Cramps;
  • Tonic-clonic seizures;
  • Feverish body temperature.

 

As the disease progresses, focal clonic seizures join. They can be a Jacksonian march and focal myoclonic seizures. They are resistant to therapy, often with a status course. Treatment-resistant seizures can be caused by hippocampal sclerosis.

 

What Causes Alper’s Syndrome

causes of alpers syndrome

Mutation of the POLG1 gene in locus 15q25 causes Alpers disease. This gene is responsible for gamma polymerase function in the mitochondria. The most common gene defects are:

  • A467T;
  • W748S. 

They differ in the age of onset of diseases and the type of inheritance and clinical manifestations. Alpers-Huttenloher syndrome is a hereditary disease with an autosomal recessive transmission mechanism. The disease predominates among conditions associated with impaired gamma polymerase DNA synthesis.

The disease is inherited through an autosomal recessive agent. So the probability of recurrence of the pathology is 25% in the subsequent pregnancy. The risk of developing the syndrome increases in closely related marriages. Scientists have not yet found thing what we call causes Alper’s syndrome.

 

Risk Factors of Alper’s Disease

The most dangerous risk factor for Alper’s syndrome is fatal toxic hepatitis. It occurs when drugs from the valproic acid group are taken to relieve seizures. Severe liver failure develops. Changes in biliary tract architectonics and liver fibrosis can indicate lesions of the hepatobiliary system. With the progression of Alper’s disease on the background of muscle, hypotonia develops:

  • dysphagia;
  • disorders of peristalsis of the gastrointestinal tract. 

There is a need for the introduction of a gastrostomy tube or the use of parenteral nutrition. Pancreatitis can complement a lesion in the digestive system. Cardiomyopathy develops in 10% of patients. It leads to severe heart failure.

 

Words from Lone Star Neurology

Alpers-Huttenloher syndrome is a rare genetic disease with a severe prognosis and symptoms within several years of clinical symptoms’ onset. Specific changes combined with features of epileptic seizures help to suspect the disease. Complete analysis of the gene allows early confirmation of the disease. Doctors from our Lone Star Neurology clinic do it by direct automated sequencing. You can always turn to our professionals for a complete diagnosis of this and other neurological diseases.

 

FAQs 

  • How is Alper’s disease inherited?

This hereditary disease has an autosomal recessive transmission mechanism. A non-hereditary mutation in one of the parents causes this disease. It can also be the development of an accidental abnormality while the child is in the womb.

  • When was Alper’s disease discovered?

Bernard Alpers, firstly in 1931, described the case of a four-month-old typically developing girl who suddenly had treatment-resistant epileptic seizures, leading to the rapid death of the child. Alpers was the first to identify the main features of the disease. The age of onset is from 3 months to 7 years, with resistant seizures, developmental regression, and amaurosis. 

  • Is Alper’s disease a neurological disease?

Yes, it is a neurological disease. It belongs to a group of diseases associated with defective mitochondrial functioning, leading to impaired body energy functions. It can also cause delays in psychomotor development, epileptic seizures, and liver damage.

  • What disorders of the neurological spectrum are similar to Alpers’ Disease?

This is myoclonic epilepsy. It is also a hereditary neurological disorder. Sudden and brief contractions of muscle groups characterize it. This disorder usually manifests itself between the ages of six and sixteen. Loss of consciousness is widespread during seizures. After many years, the frequency and severity of seizures increase. 

1 Star2 Stars3 Stars4 Stars5 Stars (No Ratings Yet)
Loading...
Lone Star Neurology
4.4
Based on 804 reviews
powered by Google
Edward Medina
Edward Medina
15:34 30 Jun 22
Just such an amazing staff that makes you feel like part of their family. I’ve been going there for over 5 years now... and each visit I get the very best care and treatments that I have ever received in the 20+ years that I’ve been dealing with severe debilitating migraines. Since i started seeing them the number of my migraines has dropped from 15-20 a month to 2-3 every 3 month. I highly recommend them …they will change your life!read more
Daneisha Johnson
Daneisha Johnson
22:20 19 May 22
Dr. Askari was very kind and explained everything so I could understand. The other staff were nice as well. I would... have gave 5 stars but I was a little taken aback when I checked in and had to pay 600.00 upfront. I think that should have been discussed in a appointment confirmation call or email just so I could have been prepared.read more
Jean Cooper
Jean Cooper
16:54 29 Apr 22
I love the office staff they are friendly and very helpful. Dr. JODIE is very caring and understanding to your needs... and wants to help you. I will go back. would recommend Dr. Dr. Jodie to other Patients in a heart beat. The team works well together.read more
Linda M
Linda M
19:40 02 Apr 22
I was obviously stressed, needing to see a neurologist. The staff was so patient and Dr. Ansari was so kind. At one... point he told me to relax, we have time, when I was relaying my history of my condition. That helped ease my stress. I have seen 3 other neurologists and he was the only one who performed any assessment tests on my cognitive and physical skills. At one point I couldn't complete two assessments and got upset and cried. I was told, it's OK. That's why you're here. I was truly impressed, and super pleased with the whole experience!read more
Leslie Durham
Leslie Durham
15:05 01 Apr 22
I've been coming here for about 5 years. The staff are ALWAYS friendly and knowledgeable. The Doctors are the absolute... best!! Jodie Moore is always in such a great mood which is a plus when you are already stressed. Highly recommendedread more
Monica Del Bosque
Monica Del Bosque
14:13 25 Mar 22
Since my first post my thoughts have changed here. It's unfortunate. My doctor and PA were great, but the office staff... is horrible. They never call you back when they say they will, they misinform you, they cause you too much stress wondering what's going on, they don't keep you posted. They never answer the phone. At this point I've left four messages in the last week, and I have sent three messages. Twice from their portal and one direct email. No response. My appointment is on Monday morning at 8:30am, no confirmation on my insurance and what's going on. What the heck is going on, this is ridiculous!I've given up... the stress her office staff has put me through is just not worth it. You can do so much better, please clean house, either change out your office staff, or find a way for them to be more efficient please. You have to do something. This is not how you want to run your practice. It leaves a very bad impression on your business.read more
Ron Buckholz
Ron Buckholz
23:32 23 Mar 22
I was actually pleasantly surprised with this visit! It took me a long time to get the appointment scheduled because no... one answers your phones EVER! After a month, I finally got in, and your staff was warm, friendly, and I was totally impressed! I feel like you will take care of my needs!read more
Steve Nabavi
Steve Nabavi
16:28 16 Mar 22
It was a nice visit. Happy staff doing all they can do to comfort the patients in a very calming environment. You ask... me they are earned a big gold star on the fridge. My only complaint they didn't give me any cookies.read more
Katie Lewis
Katie Lewis
16:10 10 Feb 22
Had very positive appointments with Jodie and Dr. Sheth for my migraine care. Jodie was so fast with the injections and... has so much valuable info. I started to feel light headed during checkout and the staff was SO helpful—giving me a chair, water, and taking me into a private room until I felt better. Highly recommend this practice for migraine patients, they know what they’re doing!!read more
Joshua Martinez
Joshua Martinez
16:02 10 Dec 21
I was scheduled to be checked and just want to say that the staff was fantastic. They were kind and helpful. I was... asked many questions related to what was going on and not once did I feel as though I was being brushed off. The front desk staff was especially great in assisting me. I'm scheduled to go back for a mri and am glad that I'll be going there.read more
Isabel Ivy
Isabel Ivy
21:42 03 Nov 21
I had such a good experience with Lone Star Neurology, Brent my MRI Tech was so awesome and made sure I was very... comfortable during the appointment. He gave me ear plugs, a pillow, leg support and blanket, easiest MRI ever lol 🤣 My 72 hour EEG nurse Amanda was also so awesome. She made sure I was take care of over the 3 days and took her time with the electrodes to make sure it was comfortable for me! Paige was also a huge help in answering all my questions when it came to my test results, and letting me know her honest opinions about how I should go forth with my treatment.read more
Leslie Luce
Leslie Luce
17:37 20 Oct 21
The professionalism and want to help attitude of this office was present from the moment I contacted them. The follow... up and follow through as well as their willingness to find a way to schedule my dad was above and beyond. We visited two offices in the same day with the same experience. I am appreciative of this—we spend a lot of time with doctors and this was top notch start to finish.read more
robert Parker
robert Parker
16:38 16 Apr 21
I love going to this office. The staff is friendly and helpful. The doctor is great. I am getting the best... neurological tests and treatment I have ever had. The only reason I did not give them a 5 star rating is because it is impossible to reach a live person at the office to reschedule appointments. Every time I have tried to get through to the office it says all people are busy and I am sent to a voicemail. If they could get their phone answering fixed, I would give them a strong 5 stars.read more
MaryAnn Hornbaker
MaryAnn Hornbaker
00:26 25 Feb 21
Dr. Harney is an excellent Dr. I found him friendly , personable and thorough. I evidently am an unusual case. ... Therefore he spent a Hugh amount of time educating me. He even gave me literature to further explain my condition and how to follow up. This is something you rarely get from your doctors. So I am more than please with my doctor and his staff.read more
Roger Arguello
Roger Arguello
03:05 29 Jan 21
Always courteous, professional. The staff is very friendly and always work with you to find the best appointment time.... The care team has been great. Always taking the time to listen to your concerns and to find the best treatment.read more
Margaret Rowland
Margaret Rowland
01:12 27 Jan 21
I have been a patient at Lone Star Neurology for several years. Now both my adult daughters also are patients there. I... love Jodie. She is always so prompt whether it is a teleamed call are a visit in the office. She takes the time to explain everything to me and answers all my questions. I am so blessed to have Jodie as my doctor.read more
Susan Miller
Susan Miller
03:01 13 Jan 21
My husband had an accident 5 years ago and Lone Star Neurology has been such a blessing to us with my husbands care.... Jodie Moore is his provider and she is amazing! Jodie is very knowledgeable, caring, and thorough. She takes her time with you, making sure your needs are met and she is happy to answer any questions you may have. Lone Star Neurology’s patients are very lucky to have Jodie providing their care. Thank you Lone Star Neurology and especially Jodie for everything you have done for us. Jodie, you are the best!read more
Windalyn C
Windalyn C
01:32 09 Jan 21
Jodie is wonderful. She is very caring and knowledgeable. I have been to over a dozen neurologists, and none were able... to help me as much as they have here. Thanks!read more
Katie Kordel
Katie Kordel
00:40 09 Jan 21
Jodi Moore, nurse practitioner, is amazing. I have suffered from frequent, debilitating headaches for almost 20 years.... She has provided the best proactive and responsive care I have ever received. My quality of life has been greatly improved by her caring approach and tenacity in finding solutions.read more
Ellie Natsis
Ellie Natsis
15:41 07 Jan 21
I have had the best experience at this neurologist's office! For over a year I have been receiving iv treatments here... each month and my nurse, Bobbie is beyond wonderful!! She's so attentive, knowledgeable, caring, and detail oriented. She makes an otherwise uncomfortable experience much more pleasant and definitely puts me at ease! She also helps me with my insurance,ordering this specialty medication and dealing with the ordering process which is no easy feat.Needless to say, she goes above a beyond in every way and I'm so grateful to this office and to Bobbie for all they do for me!read more
Matt Morris
Matt Morris
15:39 07 Jan 21
Let me start by saying that I have been coming here for years. Due to my autoimmune disease, I am in this office... once every three weeks for multiple hours at a time. The office is very clean and the staff very friendly. My only complaint would be there communication via phone. They aren't the best at responding if you leave a voicemail and expect a call back. I understand that this is prob just due to the sheer number of alls they receive daily. What I can say I like the best about the office are the people. Bobby who handles my infusions is great. I never have any issues with her setting up my infusions. She is very quick to reply to messages sent via text and if she were to leave then my whole opinion of the office may change. I also enjoy people like Matt, Lauren, and Jodi. I appreciate all that they do for me and without this team I'm not sure I would be as happy as I am to visit the office as frequently as I have to. Please ensure that these folks are recognized as they are what makes my visit to this office so tolerable :).read more
Next Reviews
js_loader

Please, leave your review

Write a comment: