Starting last month, a rare but devastating genetic disease is now part of the routine blood screening given to all California babies shortly after birth.
All of California’s newborn blood test screenings are designed to allow early detection and intervention, especially in progressive diseases that can worsen quickly, such as ALD. The blood test, usually done within a day of birth, covers 80 different genetic or congenital disorders, including cystic fibrosis, sickle cell disease and severe combined immunodeficiency, commonly called “bubble boy disease.”
Some of the tested conditions can be treated relatively easily. For instance, primary congenital hypothyroidism, a thyroid deficiency that causes babies to grow very slowly and can result in mental disability, is found in about 275 California babies annually. When detected at birth, those problems can be prevented with daily doses of special thyroid medicine.
ALD is a disease that is linked on the X chromosome. It is a result of fatty acid digestive enzymes not breaking up the fats. These fats build up in the brain. They damage the myelin that surrounds nerves. This can cause seizures and hyperactivity. It can also cause problems with speaking, listening and understanding verbal instructions.In more detail, it is a disorder of peroxisomal fatty acid beta oxidation which results in the accumulation of very long chain fatty acids in tissues throughout the body. The most severely affected tissues are the myelin in the central nervous system, the adrenal cortex and the Leydig cells in the testes. Clinically, ALD is a heterogeneous disorder, presenting with several distinct phenotypes, and no clear pattern of genotype-phenotype correlation. As an X-linked disorder, ALD presents most commonly in males, however approximately 50% of heterozygote females show some symptoms later in life.
Approximately two-thirds of ALD patients will present with the childhood cerebral form of the disease, which is the most severe form. It is characterized by normal development in early childhood, followed by rapid degeneration to a vegetative state.
The other forms of ALD vary in terms of onset and clinical severity, ranging from adrenal insufficiency to progressive paraparesis in early adulthood (this form of the disease is typically known as adrenomyeloneuropathy).
“By the time you actually develop any symptoms, the damage has already been done,” said state Sen. Richard Pan, D-Sacramento, a pediatrician who has authored three bills related to genetic testing of infants, including the ALD bill. “Being able to detect the disease at birth, it allows parents to intervene in a way that can prevent that future damage, either disability or even death.” All of California’s newborn blood test screenings are designed to allow early detection and intervention, especially in progressive diseases that can worsen quickly, such as ALD. The blood test, usually done within a day of birth, covers 80 different genetic or congenital disorders, including cystic fibrosis, sickle cell disease and severe combined immunodeficiency, commonly called “bubble boy disease.” Some of the tested conditions can be treated relatively easily. For instance, primary congenital hypothyroidism, a thyroid deficiency that causes babies to grow very slowly and can result in mental disability, is found in about 275 California babies annually. When detected at birth, those problems can be prevented with daily doses of special thyroid medicine. But ALD has no cure and can have devastating consequences. Inherited as a defective gene, it dissolves the protective myelin coating on nerve cells. Bone marrow transplants may slow or halt the disease’s progression; cortisone medications can relieve symptoms in milder cases. In young boys, the disease typically appears between the ages of 4 and 10, often getting misdiagnosed as hyperactivity, viral infections or behavioral problems. Another ALD variation, adrenomyeloneuropathy, doesn’t show up until young adulthood, often causing degenerative neurological problems that affect limbs, leading to difficulties with gait and walking. The genetic abnormality that causes ALD is carried by mothers but rarely shows symptoms in girls or women. Patti Chapman knows the disease well. She’s president of The Myelin Project, a Pacific Palisades-based nonprofit group that supports ALD research and provides financial support to affected families. She lost two brothers to ALD, one as a 5-year-old and another after adult onset at age 44. One of her four sons was diagnosed at age 8; today, at 36, he cannot walk unaided, Chapman said. “Not being able to get a diagnosis is heartbreaking and frustrating,” Chapman said. Many families “lost their boys because they didn’t know they had a predisposition.” While relatively obscure, ALD garnered attention in the 1992 movie “Lorenzo’s Oil” about a couple who developed a concoction of oleic and erucic acids, derived from grapeseed and olive oil, to treat their son’s neurological condition. That mixture has shown some benefit in slowing ALD’s progression when given to children before symptoms appear. It’s not approved by the U.S. Food and Drug Administration but is available in a clinical trial affiliated with Johns Hopkins University. California’s newborn testing program, similar to screenings done in all U.S. states, started in 1966 with testing for phenylketonuria, known as PKU. Run by the state Department of Public Health, parents are notified of their baby’s blood test results usually within two weeks. If a test is positive, a second blood test is done to confirm the diagnosis. Nationwide, it’s estimated that 1 in 20,000 newborns will test positive for ALD if all states adopt the genetic test. It’s expected that anywhere from 25 to 30 newborn boys in California will be diagnosed with ALD this year, according to state public health officials. After her 8-year-old son, Sawyer, died of ALD in 2003, Vista resident Janis Sherwood launched the FightALD website and traveled to 3,200 children’s medical facilities across the country, handing out educational brochures on the obscure disease. A decade ago, the disease was so rare that Sawyer’s symptoms went undiagnosed for months because so little information was available, Sherwood said. “Most doctors, even specialists, didn’t know about it.” Pan said parents were instrumental in pushing ALD genetic testing in California. “They’ve already had to go through that struggle, even death and grief,” Pan said. “They want to ensure that other families don’t.” ALD testing could spare other families the agony “Our boys who were lost were the catalyst for all these other boys who might be saved,” Cousineau said. “(With testing), we can stop this disease in its tracks.”