NEWBORN SCREENING FOR PILOT STUDY FOR ADRENOLEUKODYSTROPHY (ALD)

新生儿筛查的目标是在新生儿中发现可能致命或致残的疾病，从而为早期治疗提供机会，通常是在儿童仍无症状时进行治疗。这种早期发现和治疗可对受影响儿童病情的临床严重程度产生深远影响。如果不加以诊断和治疗，目标疾病的后果可能是可怕的，许多疾病会造成不可逆转的神经损伤、智力、发育和身体残疾，甚至死亡。2006年，美国医学遗传学学院（ACMG）制定了新生儿筛查指南，建议对所有新生儿进行31项“核心疾病”筛查，并报告在核心评估期间确定的26项次要疾病。这些建议已被卫生与公众服务部（HHS）新生儿和儿童遗传性疾病咨询委员会（ACHDNC）（由2000年《儿童健康法》授权）和卫生与公众服务部部长接受。大多数州现在使用这种或非常类似的小组进行新生儿筛查。目前，已经确定了数千种罕见疾病，数百种可能从新生儿筛查中受益。

The goal of newborn screening is to detect potentially fatal or disabling conditions in newborns, thereby providing a window of opportunity for early treatment, often while the child is still asymptomatic. Such early detection and treatment can have a profound impact on the clinical severity of the condition in the affected child. If left undiagnosed and untreated, the consequences of the targeted disorders can be dire, many causing irreversible neurological damage, intellectual, developmental and physical disabilities, and even death. In 2006, the American College of Medical Genetics (ACMG) developed newborn screening guidelines that recommend that all newborn infants be screened for 31 "core conditions" and that 26 secondary conditions identified during the core evaluations be reported. These recommendations have been accepted by the Department of Health and Human Services (HHS) Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) (authorized by the Children's Health Act of 2000), and by the Secretary of HHS. Most states now use this or very similar panels for newborn screening. Currently, there are thousands of rare disorders that have been identified and hundreds that could potentially benefit from newborn screening. X-linked Adrenoleukodystrophy (ALD) is one of a group of genetic disorders called the leukodystrophies that cause damage to the myelin sheath, an insulating membrane that surrounds nerve cells in the brain. Women have two X chromosomes and are the carriers of the disease, but since men only have one X chromosome and lack the protective effect of the extra X chromosome, they are more severely affected. People with X-ALD accumulate high levels of saturated, very long chain fatty acids (VLCFA) in the brain and adrenal cortex. The loss of myelin and the progressive dysfunction of the adrenal gland are the primary characteristics of X-ALD. While nearly all patients with X-ALD suffer from adrenal insufficiency, also known as Addison's disease, the neurological symptoms can begin either in childhood or in adulthood. The childhood cerebral form is the most severe, with onset between ages 4 and 10. The most common symptoms are usually behavioral changes such as abnormal withdrawal or aggression, poor memory, and poor school performance. Other symptoms include visual loss, learning disabilities, seizures, poorly articulated speech, difficulty swallowing, deafness, disturbances of gait and coordination, fatigue, intermittent vomiting, increased skin pigmentation, and progressive dementia. The milder adult-onset form is also known as adrenomyeloneuropathy (AMN), which typically begins between ages 21 and 35. Symptoms may include progressive stiffness, weakness or paralysis of the lower limbs, and ataxia. Although adult-onset ALD progresses more slowly than the classic childhood form, it can also result in deterioration of brain function. Almost half the women who are carriers of X-ALS will develop a milder form of X-ALD. Adrenal function must be tested periodically in all patients with ALD. Treatment with adrenal hormones can be lifesaving. Symptomatic and supportive treatments for ALD include physical therapy, psychological support, and special education. Prognosis for patients with childhood cerebral X-ALD is generally poor due to progressive neurological deterioration unless bone marrow transplantation is performed early. Death usually occurs within 1 to 10 years after the onset of symptoms. Adult-onset AMN will progress over decades.