TABLE 2.
Summary of results by study type
| First author (year)Citation | PKLR genes sequenced | Reported results | Prevalence estimates (per million) | Derivation |
|---|---|---|---|---|
| Population‐based prevalence study | ||||
| Carey (2000) 7 | N/A | Period prevalence: 3.2 per million | 3.2 | † |
| de Medicis (1992) 8 | N/A | Period prevalence: 1 per 117 206 | 8.5 | ‡ |
| Molecular PKLR screening study in a general population | ||||
| Beutler (2000) 10 | c.1456C > T, c.1468C > T, c.1484C > T, c.1529G > A | Estimated prevalence: 51 per million | 51 | † |
| Chami (2016) 16 | c.1456C > T | MAF for 1 PK deficiency‐causing allele: 0.30% | 9.0 | § |
| Figueroa (2018) 14 | Whole PKLR gene | MAF of 1.1% | 120 | § |
| Manco (2001) 12 | c.1456C > T | MAF of single allele: 0.325% (95% CI 0.001% to 0.649%) Estimated point prevalence: 10 per million | 10 | † |
| Svidnicki (2018) 13 | c.1456C > T, c.1529G > A | MAF for 2 common alleles: 0.10% | 1 | § |
| Molecular PKLR screening study in areas with endemic malaria | ||||
| Alves (2010) 18 | c.269T > A and c.1456C > T | MAF for two alleles: 0.0% | 0 | N/A |
| Berghout (2012) 19 | Whole PKLR gene | MAF: 1.5% (SD: 0.9%) Estimated point prevalence of PK deficiency: 1/4203 births assuming HWE | 240 | ‡ |
| Machado (2010) 17 | c.1456C > T and c.1614A > T | MAF for two alleles: 0.0% | 0 | N/A |
| Machado (2012) 20 | Whole PKLR gene |
MAF for 1 allele in children: 2.9% MAF for 1 allele in adults: 4.6% Low PK activity prevalence (Non‐molecular PK deficiency screening): 4.1% |
840 (children) § ; 2100 (adults) § ; 41 000 (Non‐molecular PK deficiency screening) ‡ | ‡ , § |
| Non‐molecular PK deficiency screening study in a general population | ||||
| Feng (1993) 32 | N/A | Point prevalence: 0.0% | 0 | N/A |
| Fox (1969) 33 | N/A | Point prevalence: 0.0% | 0 | N/A |
| Fung (1969) 31 | N/A |
Incidence/point prevalence in newborns (partial and total deficiency): 3.4% Incidence/ point prevalence in newborns (partial deficiency): 2.3% Incidence/point prevalence in newborns (total deficiency): 1.1% |
34 000 ‡ (partial and total deficiency) 23 000 ‡ (partial deficiency) 11 000 ‡ (total deficiency) |
‡ |
| Garcia (1979) 28 | N/A | Point prevalence: 0.24% | 2400 ‡ | ‡ |
| Mohrenweiser (1981) 34 | N/A | Incidence/point prevalence in newborns: 0.14% | 1400 ‡ | ‡ |
| Mohrenweiser (1987) 35 | N/A |
Incidence/ prevalence at birth using ≤ 65% normal activity threshold: 1.1% Incidence/prevalence at birth using < 50% normal activity threshold: 0.50% |
11 000 ‡ 5000 ‡ |
‡ |
| Tanaka (1971) 30 | N/A | Point prevalence: 1.4% | 14 000 ‡ | ‡ |
| Tsang (1993) 27 | N/A |
Point prevalence using modified technique: 0.0% Point prevalence using Beutler technique: 3.7% |
0 (modified technique) 37 000 (Beutler technique) |
‡ |
| Wu (1985) 29 | N/A |
Incidence/prevalence at birth (Beutler spot test): 2.2% Incidence/prevalence at birth (direct enzyme activity): 2.1% |
22 000 (Beutler spot test) 21 000 (enzyme activity screening) |
‡ |
| Non‐molecular PK deficiency screening study in areas with endemic malaria | ||||
| El‐Hazmi (1986) 36 | N/A |
Point prevalence of partial PK deficiency: 3.4% Prevalence of complete PK deficiency: 0.0% |
34 000 (partial) 0 (complete) |
¶ |
| Munyanganizi (2006) 37 | N/A | Point prevalence: 0.0% | 0 | N/A |
| Upadhye (2018) 38 | N/A | Point prevalence: 0.083% | 830 | †† |
| Non‐molecular PK deficiency screening study in areas with high consanguinity | ||||
| Abu‐Melha (1991) 44 | N/A |
Incidence/prevalence among neonates by fluorescence screening: 2.90% Incidence/prevalence among neonates by fluorescence screening and enzyme activity screening: 3.10% (95% CI: 1.5) |
29 000 (fluorescence screening) 31 000 (fluorescence screening and enzyme activity) |
‡ |
| Akin (1997) 41 | N/A |
Point prevalence of “heterozygous deficiency”: 1.10% Point prevalence of “homozygous deficiency”: 0.00% |
11 000 0 |
‡ |
| Al‐Naama (1994) 42 | N/A | Point prevalence of PK deficiency: 0.0% | 0 | N/A |
| Al‐Naama (1995) 43 | N/A | Point prevalence of partial PK deficiency among neonates: 1.4% | 14 000 (partial PK deficiency among neonates) | ‡ |
| Point prevalence of partial PK deficiency among adults: 0.0% | 0 (partial PK deficiency among adults) | |||
| Point prevalence of partial PK deficiency among all age groups: 0.82% | 8200 (partial PK deficiency among all age groups) | |||
| Point prevalence of PK deficiency among all age groups: 0.0% | 0 (complete PK deficiency) | |||
| Christensen (2010) 9 | N/A | Incidence proportion/prevalence at birth of hospital including polygamist community: 1/30 000 | 33 (total population) | ‡ |
| Incidence proportion/prevalence at birth of polygamist community: 1/250 | 4000 (polygamous community) | |||
| Implied incidence proportion/prevalence at birth of non‐polygamous population: 1 per 152 830 births | 6.5 (non‐polygamous population) | |||
| Yavarian (2008) 40 | N/A |
Point prevalence based on 60% PK activity: 1.9% Point prevalence of homozygous individuals: 0.27% |
19 000 2700 |
‡ |
| Non‐molecular PK deficiency screening in other unique population | ||||
| Mohrenweiser (1984) 45 | N/A | Point prevalence: 0.0% | 0 | N/A |
| Satoh (1983) 46 | N/A | Mutant allele frequency for all alleles: 1.4% | 14 000 | ‡ |
| Satoh (1985) 47 | N/A | Mutant allele frequency for all alleles: 0.0% | 0 | N/A |
| Molecular PKLR screening in other unique population | ||||
| Lyon (2011) 22 | Whole PKLR gene | Point prevalence: 1 PK deficiency patient out of 4 individuals studied = 25% | 250 000 | ‡‡ |
| Robinson (2010) 21 | Whole PKLR gene | Point prevalence: 1 PK deficiency patient out of 4 individuals studied = 25% | 250 000 | ‡‡ |
Abbreviations: HWE, Hardy‐Weinberg equilibrium; MAF, mutant allele frequency; PK deficiency, pyruvate kinase deficiency; PK, pyruvate kinase.
Estimate provided by study authors.
Units converted from authors’ estimate.
Estimate derived assuming HWE.
Average partial PK deficiency prevalence calculated from the individual estimates for each location.
Derived from two patients with PK deficiency among 2400 neonates.
Derived units from 1 PK deficiency case among 4 individuals sequenced.