16 November 2025
: Case report 
Hereditary Persistence of Alpha-Fetoprotein and Safe Application of Growth Hormone in Familial Short Stature: A Case Report
Mistake in diagnosis, Diagnostic / therapeutic accidents, Unusual setting of medical care, Congenital defects / diseases
Song Guo BE 1, Jun Zhang F 1, Qiuli Chen F 1, Yongguo Yu
C 2, Huamei Ma A 1*
DOI: 10.12659/AJCR.948160
Am J Case Rep 2025; 26:e948160
Table 1 Summary of HPAFP families reported in the last 42 years.
| Year | Author | Country | Reason for visit | Serum AFP | Families’ AFP | Mutation | Outcome/ follow-up |
|---|---|---|---|---|---|---|---|
| 1983 []3 | Ferguson-Smith et al | Spain | Spina bifida screening | Elevated | High serum level | −119G>A | – |
| 1986 []18 | Staples | UK | Spherocytosis and seminoma | 14–31 kU/L (16.9–37.4 ng/mL) | Elevated | – | – |
| 1990 []23 | Greenberg et al | USA | Testicular cyst | Elevated, 30–46 ng/mL | 2 siblings, and 1 daughter | – | Healthy for 6 months |
| 1993 []49 | Tokoro | Japan | Familial basal ganglia calcification | Elevated | Brother, elevated | – | Chemo-therapy |
| 1994 []16 | Feng et al | China | Health check up | 21–129 ng/mL | Father and brother, 46–198 ng/mL | – | Healthy for 1 year |
| 1997 []48 | Mal | France | Tuberculosis | 200–800 ng/mL | 637–1080 ng/mL | – | – |
| 1998 []24 | Schefer et al | Sweden | Testicular nodule | 24–30 ng/mL | 5 families, 22–51 ng/mL | – | – |
| 1999 []41 | Cochran et al | USA | Yolk sac tumor | 152.9 ng/mL | 21.40–27.70 ng/mL in father and paternal grandfather | Negative in AFP gene | Chemo-therapy |
| 2001 []19 | Fléchon and Droz | France | Seminoma testis | 31.9–42.5 ng/mL | 9–65 ng/mL | – | – |
| 2001 []19 | Fléchon and Droz | France | Testicular pain | 15 ng/mL | 12.5 ng/mL | – | – |
| 2003 []42 | Blesa et al | Spain | Asthenia | 1500 ng/mL | 8 relatives of 3 generations with 240–881 ng/mL | −119G>A | - |
| 2004 []28 | Alj et al | France | Pleurisy | 1320 UI/mL (1591 ng/ml) | 3 relatives of 2 generations with 500–880 μl/mL (602–1060 ng/mL) | −119G>A | – |
| 2004 []28 | Alj et al | Italy | Dorsal pain | 180 UI/mL (217 ng/mL) | 2 relatives of 3 generations with 420–580 IU/mL (506–699 ng/mL) | −55C>A and −65C>T | – |
| 2004 []17 | Yeh et al | Taiwan | Health check up | 143 ng/mL | 7 relatives in 2 generations with 66–322 ng/mL | Negative in AFP gene | – |
| 2004 []21 | Klümpen and Westermann | Netherlands | Testis seminoma | 20–51 ug/L | 26 μg/L in father | – | – |
| 2005 []43 | Nagata | Japen | Health check up | 516 ng/mL | 292–465 ng/mL | −119G>A | – |
| 2005 []43 | Nagata-Tsubouchi et al | Japen | Health check up | 1200 ng/mL | 1260 ng/mL | −119G>A | – |
| 2009 []44 | Li and Alexander | USA | Accelerated growth and advanced bone age | 55–88 ng/mL | 4 relatives of 3 generations with 19–39 ng/mL | – | Healthy for 2 years |
| 2010 []25 | Chierigo et al | Italy | Concerning left testicular cancer after orchiectomy | 20 to 30 μg/mL | Elevated in 4 relatives within 3 generations | - | |
| 2011 []22 | Abt et al | Switzerland | Scrotal swelling and pain | 590 μg/L (normal < 13 μg/L) | 158 ug/L in the patient’s daughter | – | – |
| 2012 []5 | Waseda et al | Japan | Testicular embryonal carcinoma | AFP remained 22 and 25 ng/mL post-orchiectomy | 20.6 ng/mL in mother | No mutation | Healthy for 3 years |
| 2012 []26 | Bonfig et al | Germany | Dysmenorrheic complaints and irregular cycles | 38.8 ng/mL | 3 relatives in 3 generations 42.2 to 60.2 ng/mL | – | None |
| 2017 []6 | Jeon et al | South Korea | – | 21.8–31.1 ng/mL | 20–90 ng/mL in 4 relatives in 3 generations | Negative in AFP gene | None |
| 2013 []47 | Rood | USA | Pregnancy | Markedly elevated | – | – | Remained elevated |
| 2017 []15 | Deshpande et al | India | Health check up | 1,830 ng/mL | 174.2 ng/mL in the son of patient | −119G>A | – |
| 2021 []45 | Patil et al | India | Health check up | 1209.5 ng/mL | 830.4 ng/mL in his son | −119 G>A | |
| 2021 []45 | Patil et al | India | NASH-related liver cirrhosis | 1298 ng/mL, cirrhotic liver | 630.2 ng/mL and 3275 ng/mL in his son and father | −119 G>A | |
| 2021 []45 | Patil et al | India | Hepatitis B-related chronic liver disease | 1475 ng/mL | 420 ng/mL in his son | −119 G>A | |
| 2022 []46 | Saracoglu et al | Turkey | Health check up | 60921 ng/mL | 52757 ng/mL in his son (30y), 65902 ng/mL (28y) and 40809 ng/mL (26y) in his daughters | – | – |
| 2024 (present case report) | Song et al | China | Short stature | 69.99–121.97 ng/mL | 63.32 ng/mL in father and 31.42 ng/mL in grandfather | No mutation | Healthy with 20 months’ rhGH treatment |
| AFP – alpha-fetoprotein; HPAFP – hereditary persistence of alpha-fetoprotein; NASH – nonalcoholic steatohepatitis; rhGH – recombinant human growth hormone. | |||||||