BILL ANALYSIS                                                                                                                                                                                                    �






                             SENATE COMMITTEE ON HEALTH
                          Senator Ed Hernandez, O.D., Chair

          BILL NO:       SB 1072
          AUTHOR:        Strickland
          AMENDED:       April 12, 2012
          HEARING DATE:  April 18, 2012
          CONSULTANT:    Orr

           SUBJECT  :  Newborn screening program.
           
          SUMMARY  :  Requires the California Department of Public Health 
          (CDPH) to expand statewide screening of newborns to include 
          screening for six types of lysosomal storage diseases (LSDs). 

          Existing law:
          1.Requires CDPH to develop a genetic disease testing program. 
            Requires newborn screening (NBS) for preventable heritable or 
            congenital disorders leading to physical defects or 
            intellectual disabilities. Requires NBS for sickle cell 
            anemia, phenylketonuria, and severe combined immunodeficiency 
            (SCID). Also requires tandem mass spectrometry screening in 
            newborns for fatty acid oxidation, amino acid and organic acid 
            disorders, and congenital adrenal hyperplasia. 

          2.Requires CDPH to establish a genetic disease unit to 
            coordinate programs in the area of genetic disease and 
            evaluate and prepare recommendations on the implementation of 
            tests for the detection of certain hereditary and congenital 
            diseases. Requires CDPH to provide genetic screening and 
            follow-up services. Allows CDPH to provide laboratory testing 
            facilities or work with qualified outside labs to conduct 
            testing.

          3.Requires CDPH to charge a fee for NBS and follow-up services, 
            and requires the amount of the fee to be established pursuant 
            to regulation and periodically adjusted. 

          4.Requires that any fee charged for screening and follow-up 
            services provided to Medi-Cal- eligible persons, health care 
            service plan enrollees, or persons covered by disability 
            insurance policies are to be paid directly to the Genetic 
            Disease Testing Fund, and are subject to the terms and 
            conditions of the health care service plan or insurance 
            coverage. 

                                                         Continued---



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          Existing regulations:  Require testing for hereditary 
          hemoglobinopathies, primary congenital hypothyroidism, and 
          galactosemia.
               
          This bill:  Requires CDPH to expand statewide screening of 
          newborns to include screening for specific LSDs: Fabry disease, 
          Gaucher disease, Hurler syndrome (MPS1), Krabbe disease, 
          Niemann-Pick disease, and Pompe disease, and makes a technical, 
          conforming change.
            
           FISCAL EFFECT  :  This bill has not been analyzed by a fiscal 
          committee.
           


          COMMENTS  :  
           1.Author's statement.  According to the author, this bill, named 
            Jacqueline's Bill, adds six lysosomal storage diseases to the 
            NBS program. These diseases can be cost-effectively screened 
            for and then parents can pursue medical treatment options 
            before the child becomes symptomatic. Treatment before these 
            children become symptomatic is vital, because treatment later 
            is not effective. The author believes that we need to give 
            parents as much information as possible. These diseases are 
            devastating and we need to let parents know as soon as 
            possible so they can pursue all available medical options.  

          2.Newborn screening.  According to the Centers for Disease 
            Control and Prevention (CDC), NBS tests infants shortly after 
            birth for serious or life-threatening metabolic and other 
            conditions that, when detected early, might be managed or 
            treated to prevent death, disability, or other severe 
            consequences such as mental retardation. These tests are 
            conducted using a few drops of blood collected from newborns 
            before hospital discharge that are spotted on filter paper 
            cards. Although NBS programs are primarily funded by user 
            fees, state and federal public health system funding often is 
            necessary to support the comprehensive programs, which include 
            education, laboratory screening, follow-up and tracking, 
            diagnosis, treatment and management, and evaluation.  

          3.Lysosomal storage diseases. According to a study in 
            Pediatrics, the journal of the American Academy of Pediatrics, 
            LSDs are rare inborn errors of metabolism that result from the 
            deficiency of one or more enzymes located within the lysosome. 
            There are over 50 identified LSDs, with a combined incidence 




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            of 1 in 1,500 to 7,000 live births. LSDs classically have not 
            been considered disorders of the newborn. However, a portion 
            of patients with LSDs can be mildly symptomatic as early as 
            the first few days of life or even before birth. The study 
            contends that it is likely that the incidence of early 
            manifestations of LSDs is vastly underestimated. LSDs are 
            sufficiently rare that most practitioners are unaware of their 
            signs and symptoms, leading to diagnostic odysseys and delayed 
            diagnoses, according to the American College of Medical 
            Genetics (ACMG).

            The recent development and availability of enzyme-replacement 
            therapy (ERT) for several of the LSDs makes diagnosis early in 
            the clinical course particularly important, according to the 
            study. The study claims that early diagnosis and intervention 
            is essential for maximizing the potential benefit from some of 
            these therapies and may prevent irreversible organ damage. 
            Early diagnosis can provide parents with realistic information 
            about their child's prognosis and can enable appropriate 
            genetic counseling for future pregnancies. 

          4.Symptoms, prognoses and treatment options. According to the 
            National Institute of Neurological Disorders and Stroke, Fabry 
            disease symptoms usually begin during childhood or 
            adolescence. The disease can cause an enlarged heart and 
            gastrointestinal difficulties and damage other organs. Fabry 
            disease often leads to premature death due to complications 
            from strokes, heard disease, and renal failure. ERT has been 
            approved to treat Fabry disease.  Estimates of its prevalence 
            in the population range from 1 in 40,000 to 50,000 but some 
            pilots have shown 1 in 1,000 to 1,500. 

            Gaucher disease is the most common of the inherited metabolic 
            disorders, and symptoms may include skeletal disorders, an 
            enlarged spleen and liver and anemia. Its prevalence is 
            estimated at 1 in 40,000. There are three subtypes of Gaucher 
            and symptoms may begin early in life or in adulthood, in part 
            depending on the type. For instance, type 1 symptoms may 
            appear at any age, and many patients may have a mild form of 
            the diseases and do not know it. Symptoms of type 2 are often 
            apparent by three months of age, and children afflicted with 
            this type usually die before age two. Patients with Gaucher 
            could require spleen removal surgery, joint replacement 
            surgery, or blood transfusions. ERT may be useful for types 1 
            and 3 only. Bone marrow transplantation can also be helpful 




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            for type 1 patients, but the procedure carries a high risk and 
            is rarely performed.

            Hurler syndrome (a subtype of MPS 1) often becomes apparent 
            between ages three and eight. Infants with severe Hurler 
            appear normal at birth, but eventually develop symptoms such 
            as cloudy corneas, deafness, halted growth, joint disease, or 
            heart valve problems. ERT is a treatment option, and bone 
            marrow transplant treatment has had mixed results. Children 
            with this disease develop nervous system problems and can die 
            young. 

            Krabbe disease most often affects infants, with onset before 
            age 6 months, but can also occur in adolescence or adulthood. 
            Symptoms include limb stiffness, seizures, vomiting, and 
            slowing of mental and motor development, and may also include 
            deafness or blindness. Infantile Krabbe disease is generally 
            fatal before age 2. The prognosis may be significantly better 
            for children who receive umbilical cord blood stem cells prior 
            to disease onset or early bone marrow transplantation. Bone 
            marrow transplantation has also been shown to benefit mild 
            cases of Krabbe disease early in the course of the disease. 
            Juvenile- or adult-onset cases of Krabbe disease generally 
            have a milder course of the disease and live significantly 
            longer. Krabbe disease is estimated to affect approximately 1 
            in 100,000 people. 

            Neimann-Pick disease has subtypes A, B, C and D. Type A, the 
            most severe form, occurs in early infancy and is characterized 
            by an enlarged liver and spleen, swollen lymph nodes, and 
            profound brain damage by six months of age. Type A has no cure 
            or treatment, and children rarely live beyond 18 months. Type 
            B usually occurs in adolescence and cause an enlarged liver 
            and spleen. Types C and D may appear early in life or develop 
            in the teen or adult years, and can cause extensive brain 
            damage. It is unknown how prevalent Neimann-Pick disease is in 
            the general population. 

            Pompe disease disables the heart and skeletal muscles.  
            Early-onset symptoms begin in the first months of life with 
            muscle weakness, poor weight gain, and an enlarged heart. 
            Babies with early-onset of Pompe disease often die from 
            cardiac or respiratory complications before age one. Clinical 
            trials have shown ERT to be an effective treatment for 
            decreasing heart size and improving muscle function. The FDA 
            also recently approved a drug to treat infants and children 




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            with Pompe disease. For individuals with late- onset Pompe 
            disease, the prognosis is dependent upon the age of onset.  It 
            is estimated to affect 1 in 40,000 people.

          5.Uniform screening panel.  In 2010, the Secretary of the U.S. 
            Department of Health and Human Services (HHS) adopted the 
            recommendation of the Secretary's Advisory Committee on 
            Heritable Disorders in Newborns and Children (SACHDNC) for a 
            uniform screening panel. There are minimum criteria required 
            for inclusion to the nationally recommended list of disorders; 
            such criteria include screening accuracy, diagnosis, 
            treatment, prevalence rate, or outcome. These recommendations 
            included screening for 30 core conditions and reporting 26 
            secondary conditions as a national standard for NBS programs. 
            SACHDNC also recommended that this panel of conditions be 
            included into all state NBS programs. The list of core and 
            secondary conditions includes metabolic disorders, endocrine 
            disorders, hemoglobin disorders, and also includes testing for 
            hearing loss and SCID.  No LSDs were included in these 
            recommendations.
            
            Some groups have submitted separate requests to SACHDNC to add 
            the individual LSDs addressed in this bill, with the 
            exceptions of Hurler syndrome and Gaucher disease, to the 
            uniform screening panel. Fabry, Krabbe, Neiman-Pick A and B, 
            and Pompe were all rejected by SACHDNC. Fabry was rejected due 
            to the variable and late onset of the disease (more than 10 
            years), the lack of published data on preventive treatment 
            early in life, some risk of immunologic response to ERT, and 
            lack of certainty that screening newborns can discern those 
            patients at highest risk of severe symptoms. For Krabbe, there 
            was lack of consensus about the case definition of the disease 
            and lack of information about the specific benefits of the 
            current treatment. Neimann-Pick A and B were rejected because 
            there was no population-based data,  discerning type A from B 
            was not always possible, there was no approved treatment, and 
            no published studies to show the efficacy of treatment in 
            humans, especially for those most likely to benefit early in 
            life. For Pompe, SACHDNC believed the screening test needed to 
            be improved, a standardized method of diagnosis after a 
            positive newborn screen should be required, and more data are 
            required about the benefit and harm of diagnosing late-onset 
            Pompe disease during infancy. 

          6.Methodology for adding new conditions.  There is no federal 




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            requirement to add a disorder to a state's screening program. 
            Some states will add a disorder once it is recommended by 
            SACHDNC, and other states wait for the official acceptance of 
            the disorder by the HHS Secretary. In California, disorders 
            have been added through legislation or administratively by the 
            CDPH director. While California typically waits for the 
            official acceptance of the disease by the HHS Secretary, CDPH 
            may also evaluate additional disorders for addition  into the 
            NBS program using the following criteria: 1) importance of the 
            health problem in terms of frequency, seriousness, and high 
            costs of care; 2) conditions associated with the disease/known 
            symptoms; 3) existence of effective treatment that improves 
            quality of life; 4) easiness of the disease detection, 
            reliably and economically; 5) adequacy of methods for 
            confirmation and follow-up.  There can be other 
            considerations, including the number of babies screened daily, 
            which may affect whether and/or when disorders are added to 
            the screening program. 

            Currently, California screens for over 70 conditions. The most 
            recent addition to California's screening program is SCID, 
            added in 2011. SCID had been added to SACHDNC's uniform 
            screening panel and CDPH had already been participating in a 
            pilot project sponsored by the Jeffrey Modell Foundation and 
            the National Institutes of Health, to begin testing newborns 
            for SCID in August of 2010. According to the March of Dimes, 
            all babies born in California since that pilot began have been 
            screened for SCID. The pilot led to seven babies being 
            identified as SCID babies, and four more babies being 
            diagnosed with T-cell lymphopenia. These data showed the rate 
            of SCID to be 1 in 35,000 in California while it was 
            previously estimated to be 1 in 100,000.

          7.Related legislation. AB 1731 (Block) would require general 
            acute care hospitals with licensed perinatal services to offer 
            to parents of a newborn, prior to discharge, a pulse oximetry 
            test for the identification of critical congenital heart 
            disease (CCHD). AB 1731 would also require these hospitals to 
            develop a CCHD screening program, as prescribed. AB 1731 would 
            also require CDPH to phase in implementation of a 
            comprehensive CCHD screening program on or after July 1, 2013, 
            and require 100 percent participation by these hospitals by 
            December 31, 2016. 

          8.Prior legislation. SB 395 (Pan), Chapter 461, Statutes of 
            2011, expanded statewide screening of newborns to include 




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            screening for SCID. 
            
            SB 1103 (Senate Budget and Fiscal Review), Chapter 228, 
            Statutes of 2004, expanded statewide screening of newborns to 
            include tandem mass spectrometry screening (TMS) screening for 
            fatty acid oxidation, amino acid, organic acid disorders, and 
            congenital adrenal hyperplasia.  

            AB 442 (Committee on Budget), Chapter 1161, Statutes of 2002, 
            requires hospitals to collect fees associated with any tests 
            conducted under the state's NBS Program.

            SB 537 (Greene), Chapter 1011, Statutes of 1998, requires DPH 
            to establish a program to provide extended newborn genetic 
            screening services for persons who elect to have, and pay for, 
            the additional screening.  

          9.Support.  Hunter's Hope, the sponsor of the bill, writes that 
            this bill is named in honor of Jacquelyn Scott, a Californian 
            who was diagnosed with Krabbe Leukodystrophy after it was too 
            late for her to receive lifesaving treatment through cord 
            blood transplantation. Hunter's Hope believes that early 
            detection through NBS for Krabbe and other lysosomal storage 
            disorders is crucial. They claim that treatment options are 
            available, however, these treatments are only effective when 
            given before symptoms become present.  Most often, children 
            are not diagnosed in time and therefore, are not able to 
            receive these lifesaving treatments.  Hunter's Hope claims 
            that by providing early diagnosis for the diseases listed in 
            this bill, hundreds of thousands of dollars, if not millions, 
            will be saved each year. 
            
          10.Opposition.  Members of an advisory panel on NBS for 
            metabolic disorders to CDPH's Genetic Disease Screening 
            Program write in opposition to this bill, claiming that the 
            available science and technology are inadequate to meet the 
            goals of this legislation. They reference SACHDNC's 
            recommendations, and claim that those decisions are based on a 
            rigorous evidence review process of the quality of the 
            screening test, the frequency of the conditions, the efficacy 
            of preemptive treatments and the cost-effectiveness of the 
            screen. They concur with the SACHDNC recommendations and feel 
            it is ill-advised to mandate testing for these LSDs at this 
            time in California. They claim that unapproved conditions like 
            these LSDs should only be screened for as part of a 




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            well-funded and monitored experimental pilot program.
            
          11.Policy concerns. 
              a.   Other LSD diseases. There are over 50 identified LSDs. 
                It is unclear why these six specific diseases have been 
                singled out for inclusion in the California NBS panel.  
              b.   Lab capacity.  ACMG contends that an essential 
                component of an LSD screening program is an experienced 
                laboratory for rapid and accurate enzymatic and molecular 
                testing. The laboratory must incorporate appropriate 
                quality assurance and proficiency testing programs 
                including sample sharing between laboratories. ACMG 
                contends that there are currently only a few laboratories 
                around the world with the required expertise and 
                experience to do this. It is unknown if the current labs 
                in California tasked with performing the existing panel of 
                required tests have the technology and capacity to add 
                these additional tests. 
              c.    Screening cost. The additional cost of adding these 
                named diseases in California is currently unknown and may 
                depend on the type of test used. For example, in Illinois 
                it was determined that $17 would need to be added to the 
                NBS fee to cover the cost of testing for 7 LSDs using 
                tandem mass spectrometry. Another testing method was found 
                to be less expensive with the reagents and equipment 
                costing about $1 per patient per test (ex: $5 for 5 LSDs), 
                but this did not include costs for technician time and 
                follow-up services. 
              d.    Adult-onset LSDs. According to ACMG, there are many 
                ethical considerations in screening newborns for LSDs. 
                They claim that screening newborns will inevitably 
                identify adult- or late-onset variants of these diseases, 
                but some of these patients may never develop symptoms or 
                require therapy. Consumers vary in their desire to detect 
                late-onset disorders in the neonatal period. Ongoing 
                counseling and support for patients and families may be 
                required to minimize the anxiety and psychosocial effects 
                of early detection for adult onset LSDs.
              e.    Care coordination for patients with LSDs. Generally, 
                care of LSD patients is coordinated by biochemical 
                geneticists or metabolic disease specialists at centers 
                equipped to handle the complex, multidisciplinary needs of 
                LSD patients. ACMG points out that such trained 
                individuals and centers are currently in short supply. 
                Even within centers, caring for LSD patients often 
                requires special expertise and facilities for the 




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                treatment of children and adults, and involves a 
                significant amount of unreimbursed time from physicians 
                and their staff. Even if the patient can be seen by the 
                appropriate specialist, they may only be capable of making 
                recommendations for testing and treatment, which must then 
                be arranged by the primary care physician- something many 
                are ill-equipped to do. Many patients must also travel 
                great distances to receive weekly or biweekly drug 
                infusions, even if a local infusion center is available.  

          12.Alternatives. In light of the outstanding issues listed by 
            SACHDNC and the concerns expressed by the geneticists on the 
            CDPH advisory panel, the author may wish to consider 
            alternatives.  One option would be narrow this bill to require 
            screening for the disease that has the most consensus in the 
            scientific community and may have the highest potential for 
            harm reduction or have the best prognoses with early 
            identification and treatment.  If this isn't clear, the author 
            may wish to direct CDPH to utilize its advisory committee to 
            assist in the evaluation of these diseases.  
               
           SUPPORT AND OPPOSITION  :
          Support:  Hunter's Hope Foundation (sponsor)
                    Association of Regional Center Agencies
                    EveryLife Foundation for Rare Diseases
                    Fabry Support & Information Group
                    National Gaucher Foundation
                    National MPS Society
                    The Peace, Love & Trevor Foundation
                    The Ryan Foundation for MPS Children
                    258 individuals

          Oppose:California Hospital Association
                    California Medical Association
                    Five individuals
          
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