8. Biotinidase Deficiency

Transcription

1 8. Biotinidase Deficiency 8.0 Introduction Screening for biotinidase deficiency is relatively young, having started only in the mid-1980 s in most programs. Screening involves the use of a semi-quantitative measurement of biotinidase activity and treatment is usually doses of oral biotin. Most screening program use the same semi-quantitative assay although variations may exist in the degrees of automation. There is little disagreement on screening cutoff levels and definitions. All data reported here was collected from questionnaires submitted to programs as noted in Chapter 3. Only programs with biotinidase deficiency screening included in their testing scheme are listed in the Tables. 8.1 Definitions for Biotinidase Deficiency Programs were asked to give the definition used by their program to define possible cases of biotinidase deficiency. In this case, there is general agreement among programs that decreased enzyme activity signals the presence of biotinidase deficiency, although there is some disagreement as to the exact level that is not normal. It is generally agreed that an abnormal screening result should result in referral to a metabolic specialist. The results of the questionnaire responses are given in Table Laboratory Procedures In order to identify laboratory procedures in use, programs were asked to report laboratory protocols and definitions for samples considered not normal. These data are reported in Table Initial Screening Results In order to ascertain the effectiveness of screening for biotinidase deficiency, programs were asked to report their findings on initial screening. Initial screening was defined as the first reportable test, and programs were asked not to include duplicate screenings. By reviewing the number of newborns screened and confirmed, versus the number of positive tests reported, the efficiency of the testing protocol may be evaluated. Additionally, programs were asked to report the number of positive patients lost to follow-up as a means of evaluating the follow-up procedures. These data are reported in Table Programs wishing to explain some of their responses included information as footnotes to the table. Because programs continue to report inaccurate or inappropriate data in some of their responses, no totals were given in some columns of the table. Some care should be taken in using these data, since not all programs reported. 8.4 Second Screen Results Please see Section 3.6 for a more complete discussion of the data on second screening tests. Second screen data are reported in Table 8.04 and are divided on the basis of whether the second screens are required on all newborns ( required ) or are obtained on some other basis ( discretionary ) when a second test is performed without regard for the initial screening result. Programs that requested a second screen because of either a certain result on the first screen that acted as impetus for a second screen or because of an unsatisfactory first screen (usually due to sample condition or early collection) were asked to report these data as repeat screens and these are also included. For each case, the data requested included the total newborns tested, the total with findings considered not normal, and the number of confirmed cases divided by type of clinical finding. It should be recognized that this is a different way of reporting these data than previously and may, therefore, be somewhat confusing. It is hoped that these data better represent the findings from additional screens. Once again, the reader is cautioned about using the data without regard to notes of explanation. 10/ NBS96

2 8.5 Cases of Biotinidase Deficiency Divided by Sex and Race/Ethnicity Programs were asked to report the total of all confirmed cases of biotinidase deficiency, whether detected on first or second screen, divided by sex and race/ethnicity. The term race/ethnicity was used because some states with high Hispanic populations maintain Hispanic data in much the same way that other states maintain racial data. These data are reported in Table For comparative data about the breakdown of births in all states and territories, the reader is referred to the tables in Chapter 1. reported in Table This table was included so that a tabulation of these data could be viewed without having to refer to several tables. 8.9 Summation of Results Table 8.09 sums the significant testing data from this Chapter. It includes the total births from Table 1.01, the total newborns reported as being screened, and the testing data reported in Tables 8.03 and Comparative percentages have been provided at the request of a number of readers, but in many cases these data are based on estimates or on data that appear to contain duplicate information, thus total compliance percentages may exceed 100% in some cases. 8.6 Time Until Treatment In order to look at overall program efficiency, programs were asked to report the number of days from birth until treatment of biotinidase deficiency. The definition of treatment used in the questionnaire was initiation of dietary or drug regimen and programs using a different definition were asked to report their definition for inclusion as a footnote to the tabulation. Similarly programs were asked to provide footnote information for any cases not treated within the first 21 days of life. These data are reported in Table Historic Data In order to document the value of screening for biotinidase deficiency, programs were asked to supply whatever historic data they could on their screening program. In particular, they were asked to give the date the program began and the number of cases detected over the years. These data are given in Table Total Newborns Screened Table 8.08 gives a summation of the data contained in Tables 8.03 and 8.04 along with the number of births in each state or territory as 10/ NBS96

3 Table 8.01: Definitions for Biotinidase Deficiency State/Territory Definition for Biotinidase Deficiency 1 Alaska Enzyme activity partially or profoundly deficient. 2 Arizona Zero or little enzyme activity. 3 Colorado Confirmed low quantitative serum biotinidase activity. 4 Connecticut Classified by treatment center. 5 Delaware Deficient biotinidase activity. Diagnosis made by medical consultant; supported by diagnostic tests. 6 Idaho Enzyme activity partially or profoundly deficient. 7 Illinois Diagnosis is determined by designated medical consultant. 8 Maryland Decreased or absent biotinidase. 9 Massachusetts Diagnosis and classification determined by metabolic consultant. 10 Michigan Complete or partial plasma biotinidase enzyme deficiency. 11 Nebraska Enzyme activity partially or profoundly deficient (wolfe). 13 New Mexico Absence of color or a color change < 30% activity control. Confirmation done by another lab. 14 New York Diagnosis and classification determined by treatment center. 15 Oregon Enzyme activity partially or profoundly deficient (Wolfe). 16 Pennsylvania a Decreased or absent biotinidase activity (confirmation by Dr. B. Wolfe). 17 Rhode Island Diagnosis and classification determined by metabolic consultant. 18 Vermont Activity persistently < 10 % normal activity. 19 Virginia Decreased or absent biotinidase enzyme. 20 Wisconsin Decreased or absent biotinidase enzyme activity confirmed by quantitative enzyme assay. 21 Wyoming Confirmed low quantitative serum biotinidase activity. a = supplemental newborn screening. 10/ NBS96

4 Table 8.02: Biotinidase Deficiency - Laboratory Testing Testing Method Other Method Definition of NOT NORMAL Definition of NOT NORMAL State/Territory (mg/dl) (mg/dl) Requiring Further Filter Paper Testing Requiring Immediate Serum Follow-up 1 Alaska Enzyme / Colorimetric 1st specimen has no color. 1st & 2nd specimens have no color. 2 Arizona Colorimetric Absent/reduced color on first. Absence of color on 2nd screen. 3 Colorado Wolf Colorimetric <30% nml adult activity on initial specimen <30% normal adult activity on initial and recall specimen. 4 Connecticut Colorimetric 20 % or less <10% or 2 results of < 20%. 5 Delaware Enzyme Enzyme activity, color change. 6 Idaho Enzyme / Colorimetric One specimen has no color. 2nd specimen together w/1st has no color. 7 Illinois Colorimetric Absence of Para amino benzoic acid. 8 Maryland Colorimetric No purple color. Two not normal filter paper testings. 9 Massachusetts Enzyme / Colorimetric < 30% enzyme activity. < 20 % enzyme activity. 10 Michigan Enzyme / Colorimetric Very little color developement. Straw or no color. 11 Nebraska Colorimetric-qualitative visual comparison < 30% 13 New Mexico Enzyme < 30% control. Between 30% - 50% activity. 14 New York Wolf Colorimetric Very little color development. No color development. 15 Oregon Enzyme / Colorimetric 1st specimen has no color. 2nd specimens together w/1st has no color. 16 Pennsylvania a Enzyme / Colorimetric Decreased or absence of biotinidase Decreased or absence of biotinidase activity. activity on second sample. 17 Rhode Island Enzyme / Colorimetric < 30% enzyme activity < 20 % enzyme activity 18 Vermont RIA 10-30% activity. < 10 % normal activity. 19 Virginia Colorimetric-qualitative Decreased or the absence of Two consecutive samples w/decreased biotinidase activity. 20 Wisconsin Colorimetric-qualitative No color. DA or the absence of biotinidase activity. 21 Wyoming Wolf Colorimetric <30% normal adult activity on initial spec. <30% normal adult activity/initial & recall. a = supplemental newborn screening. 10/ NBS96

5 Table 8.03: Initial Screening Results - Biotinidase Deficiency Number Number Number Number Newborns Newborns Newborns Newborns with with Confirmed Screened NOT NORMAL NOT NORMAL with State/Territory Test Results Test Results Biotinidase Lost to follow-up Deficiency 1 Alaska 10, Arizona 76, Colorado 83,494 a Connecticut 45, Delaware 10,794 3 N/A 1 6 Idaho 20, Illinois 192, Maryland 71, Massachusetts 82, N/A 3 e 10 Michigan 131, Nebraska 23, New Mexico 27, New York 265,167 5 N/D 1 15 Oregon 46, Pennsylvania b 82, d 0 17 Rhode Island 13,718 1 e 18 Vermont 6, Virginia 94, Wisconsin 65, Wyoming 6, TOTAL f f f 18 c a = number of screens, unduplicated count of newborns screened is not available; b =supplemental newborn screening; c = total given does not include all states; d = physician notification; e = partial; f = totals not given- too many programs reported inaccurate of inappropriate data. 10/ NBS96

6 Table 8.04: Second Screens for Biotinidase Deficiency R = Required Second Screens D = Discretionary Second Screens P = Repeat Second Screens Number Number Number Newborns Newborns Newborns of Newborns of Newborns of Newborns Receiving Receiving Receiving Total with with Confirmed State/Territory Required Discretionary Repeat 2nd NOT NORMAL NOT NORMAL with Second Second Second Screens Test Results Test Results Biotinidase Screen Screens Screens Lost to Follow-up Deficiency R D P R D P Total R D P Total R D P Total 1 Alaska 7, , Arizona 40, , Colorado N/C N/C N/C N/C Connecticut 766 a Delaware 9, , N/A N/A Idaho 12, N/A 12, Illinois N/C 0 8 Maryland 60,865 60, Massachusetts 6,369 6, Michigan 10,575 10, Nebraska DA DA 0 13 New Mexico New York DA N/C DA N/C DA N/C DA N/C 15 Oregon 42, , Pennsylvania b Rhode Island Vermont Virginia 11,725 2,971 14,696 7 a Wisconsin 2, , Wyoming DA DA N/C DA DA N/C DA DA N/C DA DA N/C Total c 112,212 85,801 13,823 d d d e a = second screen and repeat specimens combined; b = supplemental newborn screening; c = totals given reflect program responses and should be viewed as estimates only, given the number not reporting and the number of caveats listed; d = totals not given - too many programs reported inaccurate or inappropriate data; e = total given does not include all states.

7 Table 8.05: Cases of Biotinidase Deficiency Total detected on initial and second screen Subdivided by Sex and Race/Ethnicity Asian or Native White Black P. Islander American Other Unknown Total... Hispanic State/Territory 1 Alaska 0 2 Arizona Colorado 0 4 Connecticut Delaware Idaho b 7 Illinois Maryland Massachusetts Michigan Nebraska New Mexico 0 14 New York Oregon Pennsylvania a Rhode Island Vermont 0 19 Virginia Wisconsin Wyoming 0 TOTAL did not report a breakdown of Race/Ethnicity. 2 total reported is from Table 8.03 and Table 8.04; therefore total does not equal or may differ from data given in Table 8.05 and denotes a problem in reliability. 3 Ethnicity counted as a Race and is included in total. a = supplemental newborn screening; b = twins. Total Total 10/ NBS96

8 Table 8.06: Days from Birth Until Treatment Initiated for Biotinidase Deficiency Total detected on initial and second screens (blank spaces mean that no infants fell into these categories) State/Territory < >21 Unk. TOTAL 1 Alaska 0 2 Arizona Colorado 0 4 Connecticut 0 5 Delaware Idaho Illinois Maryland Massachusetts 3 10 Michigan Nebraska New Mexico 0 14 New York Oregon 0 16 Pennsylvania Rhode Island Vermont 0 19 Virginia Wisconsin Wyoming 0 1 did not report a breakdown of Days from Birth. 2 total reported is from Table 8.03 and Table 8.04; therefore total does not equal or may differ from data given in Table 8.06 and denotes a problem in reliability. 10/ NBS96

9 Table 8.07: Summation of Years Covered and Number of Cases Detected by Program Biotinidase Deficiency State/Territory Year Total Total Started Years Cases 1 Alaska NR 2 Arizona Colorado Apr /4 5 4 Connecticut Delaware NR 6 Idaho Illinois Maryland Massachusetts Michigan Nebraska New Mexico New York Oregon Pennsylvania a Rhode Island NR 18 Vermont Jul / Virginia Wisconsin Wyoming Apr /4 1 a = supplemental newborn screening. 10/ NBS96

10 Table 8.08: Total Newborns Screened for Biotinidase Deficiency Number Number Number of Newborns of Newborns of Newborns Total with with Confirmed Births NOTNORMAL NOT NORMAL with State/Territory Test Results Lost to follow-up Biotinidase Deficiency 1 Alaska 9, Arizona 75, Colorado 56, Connecticut 44, Delaware 10,651 4 N/A 1 6 Idaho 18, Illinois 180, Maryland 67, Massachusetts 81, Michigan 132, d 11 Nebraska 23, , New Mexico 26, New York 265,368 5 N/D 1 15 Oregon 45, Pennsylvania b 148, c 1 17 Rhode Island 13, Vermont 6, Virginia 90, Wisconsin 66, Wyoming 5, TOTAL 1,393, a a = total given does not include all states; b = supplemental newborn screening; c = physician notification; d = 2 classic and 5 partial. 10/ NBS96

11 Table 8.09: Summation Results of Testing for Biotinidase Deficiency Total % of Total % of Total % of Total % of Total Newborns Newborns Newborns Newborns Newborns Newborns Newborns Newborns Births Receiving Receiving Receiving Receiving Receiving Receiving Receiving Receiving Initial Initial Required Required Discretionary Discretionary Repeat Repeat State/Territory Screen Screening 2nd 2nd scrn. 2nd 2nd scrn. 2nd 2nd scrn. calculated Screen (calc'd) Screen (calc'd) Screen (calc'd) 1 Alaska 9,933 10,053 * % 7, % % 2 Arizona 75,127 76,060 * % 40, % % 3 Colorado 56,059 83,494 * % 4 Connecticut 44,327 45,628 * % % 5 Delaware 10,651 10,794 * % 9, % % 6 Idaho 18,252 20,176 * % 12, % % 7 Illinois 180, ,283 * % 8 Maryland 67,765 71,426 * % 60, % 9 Massachusetts 81,212 82,018 * % 6, % 10 Michigan 132, , % 10, % 11 Nebraska 23,487 23, % 25, New Mexico 26,819 27,358 * % % % 14 New York 265, , % 15 Oregon 45,677 46,419 * % 42, % % 16 Pennsylvania c 148,985 82, % % 17 Rhode Island 13,574 13,718 * % % 18 Vermont 6,461 6, % % 19 Virginia 90,160 94,835 * % 11, % 2, % 20 Wisconsin 66,120 65, % 2, % % 21 Wyoming 5,867 6,114 * % TOTAL a 1,393,677 1,354,705 b 112,212 b 85,801 b 13,823 b * Percentage > 100% denotes inability of program to separate newborns screened from specimens received; a = totals should be viewed as a rough estimate due to inability of many states to know actual number of Newborns screened. Many programs count samples received but cannot eliminate duplication when multiple samples are received; b = cannot be calculated due to inaccurate data; c = supplemental newborn screening. 10/ NBS96