Table 1.
Clinical, genetic, and immunological characteristics of the 14 APECED patients.
| Pt | Gender | Age (years) | Age at referral (years) | Major APECED diseases | Other clinical manifestations | Auto Abs | IFN Abs | AIRE gene pattern*/protein | Therapy |
|---|---|---|---|---|---|---|---|---|---|
| 1. (13) | M | 6.5 | 5.4 | Acute liver failure (5), hypergammaglobulinemia, autoimmune hepatitis (5), onychodystrophy (6) |
AADC, IA2Ab, SMA, ACA, SCC Ab, 21OHAb, AADC, cP4501A2Ab pos
TgAb, TPOAb, IAA, GADAb, ZnT8Ab, AGA, ENA, ANA, ANCA, AMA, ARA, dsDNA, LKMAb, LC1Ab, RAb, SLA-IgG, PCA, 17αOHAb, HarmoninAb, VillinAb, TPHAb, cP4502D6Ab, cP4502A6Ab neg |
IFNω IFNα4 pos | het c.967_979del13 (L323SfsX51) het c.1259_1260delTG (V420GfsX3) | Prednisone Omeprazole Azathioprine Ursodeoxycholic acid Calcifediol |
|
| 2. | F | 14.1 | 7 | CH (7), CMC (13) | HT (7), vernal keratoconjunctivitis (10), vitiligo (11), selective partial IgA deficit (12), autoimmune hepatitis (13), hypertransaminasemia, hypergammaglobulinemia |
TPHAb, AADC, TgAb, TPOAb, ANA, ACA, 17αOHAb, SSA, cP450c21Ab pos
TRAb, IAA, GADAb, IA2Ab, TRGAb, ANCA, SMA, ARA, dsDNA, LKMAb, LC1Ab, RAb, SLA-IgG, PCA, IFA, SCCAb, HarmoninAb, VillinAb, cP4501A2Ab, cP4502D6Ab, cP4502A6Ab neg |
IFNω IFNα4 pos | het c.769C>T (R257X) het c.1616C>T (P539L) |
Prednisone Hydrocortisone Fludrocortisone Ursodeoxycholic acid Azathioprine Calcitriol Levothyroxine (LT4) Lansoprazole Fluconazole |
| 3. (14) | M | 13.2 | 9.8 | Autoimmune hepatitis (9), hypertransaminasemia, hypergammaglobulinemia |
AADC, ANA, ACA, SMA, IFA, SCCAb, cP450c21Ab, AADC, cP4501A2Ab, cP4502D6Ab, cP4502A6Ab pos
TgAb, TPOAb, TPH, IAA, GADAb, TRGAb, ENA, ANCA, AMA, ARA, dsDNA, LKMAb, LC1Ab, ASCA, RAb, SLA-IgG, PCA, 17αOH Ab, HarmoninAb, VillinAb, TPHAb neg |
IFNω
IFNα4 |
het c.415C>T (R139X) het c.967_979del13 (L323SfsX51) |
Prednisone Lansoprazole Azathioprine |
|
| 4. (14) | M | 20.1 | 11.6 | CH (7), AD (17) | Septic arthritis (3), transient GH deficiency (9), autoimmune hepatitis (12), hypergammaglobulinemia, alopecia (16) |
ACA, LKMAb, PCA, IFA, 17αOHAb, SCCAb, cP450c21Ab pos
AADC, TgAb, TPOAb, TPH, IAA, TRGAb, AGA, ANA, ANCA, SMA, AMA, ARA, dsDNA, ASCA, RAb, LC1Ab, SLA-IgG, HarmoninAb, VillinAb, AADC, TPHAb, cP4501A2Ab, cP4502D6Ab, cP4502A6Ab neg |
IFNω | het c.415C>T (R139X) het c.967_979del13 (L323SfsX51) |
Hydrocortisone Calcitriol Fludrocortisone Calcium carbonate Folic acid Acetylsalicylic acid |
| 5. (14, 20) | M | 20.9 | 1.6 | CH (5), AD (5), CMC (5.5) | Autoimmune hepatitis (1.5), vitiligo (5), alopecia (5), enamel dysplasia (5), nail pitting (5.5), chronic diarrhea/malabsorption (5.5), alternation constipation/diarrhea, autoimmune gastritis (6), keratoconjunctivitis (6), previous PRES (6), periodic rash-associated fever (7), cholelithiasis (11), GH deficiency (11), primary testicular failure (14), early hypertension (14), kidney cysts (14), nasal polyps (15), keratitis, HT, urticaria |
TPHAb, AADC, Thyroid Ab, PCA, IFA, 17αOHAb, cP4501A2Ab, cP4502A6Ab pos
TRGAb, ICA, GADAb, IA2Ab, ENA, ANA, ANCA, SMA dsDNA, LKM, SCCAb, HarmoninAb, VillinAb, cP4502D6Ab neg |
IFNω IFNα4 | homo IVS1 + 1G>C; IVS1 + 5delG | Calcitriol Calcium LT4 Hydrocortisone Prednisone Fludrocortisone anti-hypertensive therapy Anti-fungal therapy |
| 6. (14, 21) | F | 19.4 | 4 | CMC (4), CH (4), AD (15) | Nail pitting (4), alopecia (11), HT, onychodystrophy, alternation constipation/diarrhea |
AADC, Thyroid Ab, GADAb, IA2Ab, 17αOHAb, 21OHAb pos
TRGAb, ICA, ENA, dsDNA, PCA, IFA, SCCAb, HarmoninAb, VillinAb, TPHAb, neg |
IFNω IFNα4 pos | homo IVS1 + 1G>C; IVS1 + 5delG | Calcitriol Calcium LT4 Hydrocortisone Prednisone Fludrocortisone iron sulfate vitamin C, B6, B12, folic acid supplement Anti-fungal therapy |
| 7. (14) | F | 21.3 | 2 | CH (2), CMC (3), AD (3) | Dental enamel dysplasia (3), nail pitting (3), GH deficiency (11.5), primary ovarian failure (12), keratoconjunctivitis (12), chronic constipation (17), frequent abdominal pain, previous Helicobacter pylori infection (17), relapsing urticaria, onychodystrophy, hypolacrimia, peripheral retinal degeneration, recurrent headaches |
TPHAb, GADAb, SCCAb, cP450c21Ab pos
TRGAb, Thyroid Ab, ICA, IA2Ab, ENA, ANA, ANCA, SMA, dsDNA, LKMAb, PCA, IFA, 17αOHAb, HarmoninAb, VillinAb, AADC, cP4501A2Ab, cP4502D6Ab, cP4502A6Ab neg |
IFNω IFNα4 pos | het c.62C>T (A21V) het c.967_979del13 (L323SfsX51) |
Hydrocortisone Fludrocortisone Calcitriol Calcium estrogen and progestin Fecal softeners anti-fungal therapy |
| 8. (15) | M | 22.5 | 1 | CMC (1), CH (11) | Autoimmune enteropathy with malabsorption (DQ2/DQ8) (6), hypertransaminasemia (7), iron-deficiency anemia (9), IgA deficit (9), carpal spasms (11) |
TPHAb, AADC, Ro2Ab, pos
Thyroid Ab, 17αOHAb, SCCAb, HarmoninAb, VillinAb, cP4501A2Ab, cP4502D6Ab, cP4502A6Ab neg |
IFNω IFNα4 | homo c.1566 + 2-1566 + 3insT | Calcium carbonate Calcitriol |
| 9. | F | 14.2 | 1 | Oral CMC (4), CH (7) | Alopecia (1), onychodystrophy (1), abscesses (4), joint pain (8), chronic mucous diarrhea (9), growth deficit | TgAb, TPOAb, IAA, ACA, ANA, 21OHAb (cP450c21Ab), cP4502A6Ab pos GADAb, PCA, IA2Ab, ovaryAb, 17αOHAb, SCCAb, HarmoninAb, VillinAb, AADC, TRGAb, TPH Ab, cP4501A2Ab, cP4502D6Ab neg | IFNω neg IFNα4 pos |
homo c.64_69delGTGGAC (V22_ D23del) | Calcium carbonate Calcitriol 0.5 rhGH treatment HRT |
| 10. | F | 9.5 | 1 | CMC (1), CH (8) | Still’s disease (1), chronic mucous diarrhea (6), psoriatic onychopathy (6), macrocytosis (7), homo MTHFR mutation c.677C>T (7), autoimmune gastritis (9) |
TPHAb, AADC, GADAb, ANA, IFA pos
TgAb, TPOAb, TRAb, IAA, IA2Ab, ZnT8Ab, ACA, ENA, ANCA, P-ANCA, C-ANCA, SMA, AMA, dsDNA, ASCA, LKMAb, LC1Ab, PCA, 17αOH Ab, SCCAb, HarmoninAb, VillinAb, TRGAb, cP450c21Ab, cP4501A2Ab, cP4502D6Ab, cP4502A6Ab neg |
IFNω IFNα4 | het c.47C>T (T16M) het c.769C>T (R257X) |
Calcitriol Magnesium supplement once a day Vitamin A, B6, B9, B12, C, D, zinc, iron, copper, and selenium supplement Calcium carbonate Omeprazole |
| 11. (16) | F | 28.7 | 13 | CMC (0.1), CH (6), AD (8) | T1D (3.6), gastrointestinal dysfunction (3.9), temporal lobe epilepsy (4.7), hypercholesterolemia (5.6), constipation (5.8), ocular myasthenia (5.8), onychodystrophy (5.8), precocious puberty (6.6), HT (9.7), iron-deficiency anemia (20), secondary amenorrhea (21), alopecia (21), homo MTHFR mutation c.677C>T (22.6) |
TPHAb, AADC, TgAb, TPOAb, IAA, ICA, GADAb, IA2Ab, ACA, ovary Ab, 21OHAb pos
TRGAb, AGA, ANA, ANCA, SMA, EMA, AMA, ARA, LKMAb, LC1Ab, RAb, PCA, IFA, cardiolipin Ab, 17αOHAb, SCC Ab, cP4501A2Ab, cP4502D6Ab, cP4502A6Ab neg |
IFNω IFNα4 pos | homo c.415C>T (R139X) | Insulin aspart Insulin degludec Hydrocortisone Fludrocortisone Calcitriol Calcium carbonate Clobazam Levetiracetam Lacosamide Carbamazepine Pyridostigmine bromide Lansoprazole Ezetimibe/Simvastatin Estradiol valerate/dienogest |
| 12. (17) | M | 34.2 | 5 | CMC (6), AD (15) | Onychosis (Candida albicans) (6), low-grade chronic active autoimmune hepatitis (8), hypertransaminasemia, hypergammaglobulinemia, obesity, and short stature (due to long-term steroid treatment) (12), central diabetes insipidus (15) |
TPHAb, AADC, SMA, LKMAb, 21OHAb (cP450c21Ab), cP4501A2Ab, cP4502D6Ab pos
TgAb, TPOAb, IAA, GADAb, IA2Ab, TRGAb, ANA, AMA, ARA, RAb, mitochondrial Ab, other organ and non-organ specific Ab, 17αOHAb, SCCAb, HarmoninAb, cP4502A6Ab neg |
IFNω pos
IFNα4 neg |
homo c.1314-1326del13/insGT (D439CfsX61) | Fludrocortisone Prednisone Omeprazole Desmopressin |
| 13. | F | 22 | 19.7 | CH (3), CMC (4) | Autoimmune hepatitis (4), hypertransaminasemia, hypergammaglobulinemia |
TgAb, TPOAb, LKMAb pos
IAA, GADAb, IA2Ab, TRGAb, ZnT8Ab, ACA, ANA, ANCA, SMA, EMA, LC1Ab, ASCAb, RAb, SLA-IgG, Sp100Ab, gp21Ab neg |
ND | het C322fsX372/C449Xhet 964-976del13 | Azathioprine Prednisone Calcium lactate/gluconate Calcitriol |
| 14. | M | 11.1 | 9 | CH (4) | Urticarial vasculitis (0.8), vitiligo (7), autoimmune hepatitis (8), autism |
TPOAb, ACA, ANA pos
ANCA, SMA, AMA, ARA, RAb, LKMAb, LC1Ab, SLA-IgG, PCA neg |
ND | het c.47C>T (T16M) het c.967_979del13 (L323SfsX51) |
Azathioprine PTH Calcium carbonate Calcitriol |
In brackets, the age of onset of disease symptoms is shown. In bold, positive values.
Het, heterozygous; homo, homozygous; neg, negative; pos, positive; ASCA, anti-Saccharomyces cerevisiae Abs; HT, Hashimoto thyroiditis; GH, growth hormone; PRES, posterior reversible encephalopathy syndrome; U, unit; IU, international unit; HRT, hormone replacement treatment.
*Mutations and polymorphisms.