Alpers Disease is described by Dr Bernard Alpers in year 1931. Then in year 1976 Dr Peter Huttenlocher described the clinical features. For this reason, this disease is named Alpers Disease or Alper-Huttenlocher disease also. This disease is a rare disease that may seen in 1 of 200000 births. It is inherited with autosomal recessive inheritance. Because of autosomal recessive inheritance this disease is more common in consanguineous marriages.
This disease is transferred with autosomal recessive inheritance. For having a diseased children, the defective gene must transferred from both of the parents. If anyone of the children have this disease, the other child will have the disease by %50 percent also. In this patient’s POLG (Polymerase gamma gene) gene is defective. POLG gene have encoded in chromosome 15. In the other hand, MPV17 (Encodes a small mitochondrial membrane protein of unclear function) gene, DGUOK (Deoxyguanosine kinase) gene, Twinkle gene (Mitochondrial DNA helicase) in infancy, TK2 (Thymidine kinase) gene, SUCLA2 (ATP-dependent succinyl-CoA synthase) gene, SUCLG1 (GTP-dependent succinyl-CoA synthase) gene and RRM2B (p53-dependent ribonucleotide reductase) gene defects arre the most common identified gene defects. Over 100 mutations of this gene have reported. These mutations causes to different pathologies during the replication of the mitochondrial genome.
For these reason, many different symptoms may seen in this patients. With the malfunction of this gene, Polymerase gamma protein alpha subunit will produced irregularly. Polymerase gamma is functioning inside the mitocondria. It works in oxidative phosphorylation cascade also. For this reason, if this gene is defective the foods cannot turned to energy. With it, many symptoms will occur in these patients in infancy. In the other hand,
The most common onset age range is 2 to 4. But in some patients it may start after 20 years of age. Brain degeneration of the gray matter have always reported. Brain structures will shrink and brain spinal fluid amount will decrease. So, the first sign of the disease is resistant seizures with delaying in the developmental stages. In electroencephalography showing multifocal paroxysmal activity with high-amplitude slow delta wave may seen. Lactate level in blood or cerebrospinal fluid may measured elevated. With it, progressive mental retardation, spasticity and dementia will also seen. Headaches, sleepiness, lethargy and irritability may seen also. Optic atrophy that usually causes to blindness can seen. Over time, hearing will reduce also.
Impaired functioning of digestive system may develop also. Nausea and vomiting may occur in these patients. Clinical signs may observed due to liver function deteriorates. The patients usually dies due to unstoppable persistent seizures or progressive hepatic failure in childhood. With it, sometimes these patients may also die due to cardiorespiratory insufficiency. The patients may usually die in first decade of life.
This disease has no complete cure treatment. There is no way to slow the progression also. Antiepileptic drugs may used for seizures. The seizures may not respond to therapy well. Valproate may not used because of liver toxicity. Physical therapy and antispasmodics may used for spasticity.
In 1 of 5 patients the severity of this disease is low. These patients will diagnosed in age of 20 to 30.
With it, all of the studies says that the prognosis for Alpers Disease is poor.